Paper - Quantitative chemical changes in the human brain during growth (1919)
MacArthur CG. and Doisy EA. Quantitative chemical changes in the human brain during growth. (1919) J Comp. Neurol. 30: 445-.
Quantitative Chemical Changes In The Human Brain During Growth
C. G. MacArthur, and E. A. Doisy
The Biochemical Laboratory of the University of Illinois, and Stanford Medical School
Three Charts
It seemed desirable to develop a more complete growth series of quantitative determinations of the important constituents in the human brain than has heretofore been published (KochMann, '07- '08). During fetal life and infancy these changes are most interesting, but least studied. The chemical differentiation during growth in young pigs (Koch, '13) and young rats (W. and M. L. Koch, '13) has received attention, but early human life has been curiously neglected.
Method of Analysis
The method of analysis is essentially the same as that used by others in quantitative brain work.^ The outline on page 446 gives the main points.
Limitations and Errors
It needs to be kept in mind that disease caused the death of the people whose brains were analyzed. Though the brain in no case showed appreciable lesions, yet it is always possible that chemical alterations might have taken place before death.
Only one brain (except in the case of the three-month fetal brains) was analyzed for each of the ages given. Of course there is no guarantee that each was an average brain. Moreover, we have, because of the few analyses, no means of finding out the average deviation. Not until many such series have been developed shall we be able to state what normal brain growth really is. To a certain extent, a smooth curve averages the data, but this may introduce larger errors than it attempts to average. There is no way of knowing definitely that a curve should be regular as given or made up of a series of waves of different sizes. This also can be determined only by a larger number of investigations.
- For detail of method and formulae for calculation of results see Koch, W., J. Am. Chem. Soc, 31, 1329, ff. 1909; Koch, M. L., and Voegtlin, C, Hyg. Lab. Bull. No. 103, p. 67. 1916.
Moist brain tissue
Add alcohol and extract alternately with alcohol and ether
EXTRACT^ (fractions 1 AND 2)
RESIDUE (fractions 3 AND 4)
Evaporate to dryness, emulsify with water, precipitate with CHCI3 in 0.5 per cent HCI solution
Dry, weigh, and extract with hot water.
Precipitate (fract.l): (Colloidal)
Filtrate (fract 2): (Crystalloidal)
Filtrate (fract 3) : (Crystalloidal)
Residue (fract. 4): (Colloidal)
Lipoids
Organic constitu
Inorganic constit
Proteins
Phosphatids
ents:
uents :
Nucleoprotein (a)
Cerebrosides
Hypoxanthin
Ammonium
Nucleoprotein (b)
Sulphatids
Tyrosin
Iron
Neurokeratin
(Cholesterol, etc.)
Leucin
Sodium
Urea
Potassium
Inosit
Calcium
Taurin
Magnesium
Peptones
Chlorides
Sarcolactic acid
Inorganic constituents (see fract. 3)
Organic constituents (see fract. 2)
Lipoid sulphur
Neutral sulphur
Inorganic sulphur
Protein sulphur
(Sulfates)
Lipoid phosphorus
Organic extractives
Inorganic phosphorus (Phosphates)
Protein phosphorus
Phosphorus
Lipoid nitrogen
Organic nitrogen
Inorganic nitrogen
Protein nitrogen
2 Substances in italics were determined in this investigation.
If the thirty-five-year-old brain is normal, there is a rather wide range of variability. It will be noticed that the total solids in this brain are 5 per cent higher than in the other adult brains. This cannot be an analytical error, because the same amount was obtained in two analyses made at different times in the series.
The brain marked '8-24 mo.' was labeled '2 years' when sent for analysis. There seems to be no good reason for questioning the accuracy of this information. However, the weight of the brain indicates an infant of a few months. Its water content suggests an infant of about eight months, while some of the phosphatids would favor a slightly greater age, as would the weight of cerebellum and stem. Very likely this brain was two years old, but subnormal. In spite of the uncertainty concerning the brain, it is included in this series because it was the only one of this age available, but it is considered with the greatest reservation in forming general conclusions.
No brains about five and twelve years of age could be obtained. This leaves the series incomplete.
Unfortunately, it was not known until the investigation was nearly finished that the method used for sulphur determination gave low results. This vitiates to a certain extent the reports on the various forms of sulphur, the sulphatids, and because of the methods of calculating the data, the cerebrosides, and the undetermined cholesterol. It was planned to make direct cholesterol estimations, but the series took so much longer than expected that these estimations were omitted.
Analyses 7 and 10 were made together. A combination of circumstances tendered their phosphatid determinations somewhat unreliable. If the solutions to be precipitated by chloroform and hydrochloric acid become too warm and are allowed to stand too long, the phosphatids are incompletely precipitated. This gives not only an error in phosphatids, but, by difference, in 'cholesterol, etc' and in extractives.
Many ways were found of improving the method after beginning this series, but they could not be adopted because of the effect on comparisons of results. One always sees many ways of improving an investigation after it is finished, and that is unusually true of this investigation.
Description of Material
Dr. H, Gideon Wells, of the Pathological Department of the University of Chicago, very kindly arranged to help us in this investigation. Without his cooperation, this series would have been very incomplete.
Upon receipt of a brain the meninges and blood were removed from the brain and it was divided into forebrain, cerebellum, and brain stem, and each division weighed. Samples were then taken and placed in enough 95 per cent alcohol to make the concentration 85 per cent alcohol. The specimens were as follows:
Three-month fetus. Male. Two three-month fetuses, referred to as normal, were united in order to furnish material enough for one good analysis. These brains were not divided into forebrain, cerebellum and brain stem.
Seven-month fetus. Female. The mother of this stillborn fetus entered the hospital five days before the dehvery with signs and symptoms of placenta praevia. A brain of this age also give^ too small amounts if separated into divisions, so such separation was not made.
One-month child. Male. This child died of bronchopneumonia. The forebrain was separated from the rest of the brain, the cerebellum and brain stem were analyzed together because there was not enough in either to make a satisfactory separate analysis.
Three-month child. Male. Died of bronchopneumonia and marasmus.
Eight to twenty-four month child. Male. Though there was no record of this child having been abnormal, the brain was found to be decidedly underweight for the two-year age reported. The child may not have been two years old, but younger. More Hkely it was subnormal.
Twenty-one year adult. Male. Died of pneumonia. The autopsy did not take place for three days after death, but the weather was cool, so the brain was in good state of preservation when received.
Thirty-three year adult, (negro). Male. Died of acute pneumonia. No other disease was present.
Thirty-five year adidt (Hungarian). Male. Cause of death not reported. Brain was very high in solids, but not pathological in any evident way.
Sixty-seven year adult. Male. Died of tuberculosis.
The weights of the different divisions obtained from these brains were as follows :
Whole brain: Weights of divisions in grams
Whole brain. Forebrain. . .
Left
Right
Cerebellum. . Brain stem. .
FETUS
3
MONTHS
FETUS
7
MONTHS
CHILD
1 MONTH
CHILD
3
MONTHS
CHILD'
8
MONTHS
ADULT
21 YEARS
ADULT
33 YEARS
ADULT
35 TEARS
17.08
119.0
457.4
585.2
492.5
1122.4
1221.3
1158.3
395.0
514.0
409.0
950.0
1026.0
986.0
200.0
263.0
206.0
485.0
516.0
510.0
195.0
251.0
203.0
465.0
510.0
476.0
(37.4)4
42.6
48.2
111.4
130.6
110.8
(25.0)4
28.5
35.3
61.0
64.7
61.5
ADULT
65 TEARS
1297.9
1075.0
535.0
540.0
145.4
77.5
^ See section on Limitations for explanation.
Analyzed together because of small amounts of each.
Discussion of Results
Water and total solids
The water determinations show that though the absolute amount increases (table 12, fig. 1), the percentage of this constituent decreases continually (table 10) until growth is completed. The relative amount of water present is an indication of the rate of activity. Water, like the inorganic salts and the simpler organic substances (table 10), decreases relatively rather regularly with the approach to adult condition and its decrease in rate of metabohsm.
The percentage of total solids of course varies inversely with that of water. The increase is largely due to the formation of the colloidal substances. They increase in absolute amounts (table 12, fig. 1) and in percentage (table 10), while the simpler molecules, as a rule, decrease in percentage, but increase in absolute quantity. It will be noticed from table 13 and figure 2 that the solids are formed most rapidly soon after birth; at least 0.5 grams a day are then being added. This coincides with the period of most rapid myelination.
It does not necessarily follow that this is the time of greatest protoplasmic activity, because under other conditions the products of the reaction may be removed, while during the period of myelination a part may form the sheath.
It needs to be remembered that the substances produced in myelination are not to be thought of as active protoplasmic compounds in the same way as the extractives, certain lipins, and nucleoproteins. This is true whether one considers the sheath as nutritional or insulating in function. In comparing nerve activity with other tissues, it would probably be more exact, therefore, to use data on the axis cylinders and not the whole nerve (Donaldson, '16).
Wt in gms.
80
72
64
56
48
+0
32
i+
16
1 1 1 1 1
Kjrdpn I
^^
r totems ^*^ -^
^XT_ ^'^
^ /
<^ ."^
^"^ /;r.;^c--v^
. ^ Lipins^ ^
/ 7
^^ ^^
.^ ^"^
^^ ^^
-y^lt ^^
y y x
/ ^
/ ^ x^
. t' Hk , ,r ,/,',/, - — V ^n^
y ^ rnosphatias y^
1 / ^^ 1
-f f- ^ -~] LXcf^ct/ves~
tt ^-*' ^—
t ^^"2"
T ^^^ ^^^
It ^ OuiphdCias ^ — '^
H r ^«-""^
Jfi -'"'
J6
24- 32
1/ me In months Fig. 1
40
48
56
Milligrams added per day
lay
1 M 1 M 1 1 11 1 1 1 M 1
Grap
A
"yriit
100
^rotein
'1
c
s
Itfbfl
T^
I i
77
^ .
^otal Lif
M
1 V '
if _^
-V 4
WT
UA it
1/ f
t t
~
1/ /
t.^.t
fi 1
4 V A
Daraclives
11/
4 A
ill
4 i
III
i I
lii
V
III
A
I
[//
fW
OO
W^
r A
f /
Yl a
y
iti
Tr
r
1
[TT
y )
rnospfiduos
Iri
At
\ ^
I
J Jl-.
Vv I
\
L inynhrn'^^inoc "^nH
1 \ I —
-V
40
A
^ ouipndvios
12 16 20
T/me in months Fig. 2
24
28
Phosphatids
Lecithin (MacArthur and Darrah, '16), cephalin (MacArthur, '16), sphingomyelin and myeUn are the principal phosphatids found preformed in the brain. Some or all of these compounds are present from very early fetal life (table 1). They gradually increase (table 12) until myelination becomes rapid, then they are formed at the maximum rate of 0.1 gram per day (table 13). They continue to be formed rapidly until two years of age; after this the rate decreases to adult age. During adult life they probably increase very slowly and are one of the colloidal factors to be considered in retarding metabolism in old age.
We have some reasons for beUeving that lecithin is the phosphatid largely found in the nerve cells (Cowdry, '14). It looks as though it were rather closely associated with the nucleoproteins in carrying on vital activities. Cephalin is probably present in both the cells and axis cylinders, though more largely in the latter. Very little is known about sphingomyelin, but it it is probably largely to be found in the sheaths. It would be very interesting to study the increase in each of these phosphatids during growth.
Lecithin, and especially cephalin, because of their auto-oxidation characteristics, are believed to be closely related to nervetissue oxidation (Signorelli, '10; MacArthur and Jones, '17).
Cerebrosides
Phrenosin (Levine and Jacobs, '12) and kerasin (Rosenheim, '13), the two brain cerebrosides, may be parts of an unstable complex made up of sulphatid, phosphatid, and cerebroside. If this is true, the data in this paper would indicate that with growth this complex increases in complexity (fig. 1), because the cerebrosides as analyzed do not appear until birth (tables 2, 5, and 8), when myelination becomes the dominant brain activity. This may mean that they are in some way dependent on the presence of other constituents for their production. They are peculiar in the rapidity with which they assume such a prominent place in developing nerve tissue.
The cerebrosides are probably more directly related to sheath formation than any other constituent (Smith and Mair, '12- '13). Their maximum rate of formation does not occur as early as in the case of the other brain constituents (at four months instead of at birth) (table 11). Then about 0.025 gram are added each day.
Sulphatids=
Because of uncertainty concerning the sulphatids found in the brain, the report for this constituent is open to question. It is assumed, however, that it is a cerebroside and phosphatid fastened together by a sulphate radicle (Koch, '10). The sulphatids are very closely related to the cerebrosides in physiological function and anatomical distribution. The sulphatids seem to be more fundamentally necessary because they are found earlier (table 10). They may be related to conductivity in axis cylinders. Small amounts are present in very early fetal life (tables 1, 4, and 6). Soon after birth the amounts formed are greatest (table 12), but there is no time during life when this compound is not being produced. Probably it is concerned in the rivalry between structure and function, helping the former to victory in stability of activity, and finally in death. This is one of those substances so necessary for highly specialized brain work, but so detrimental to continued growth.
Proteins
The most important protein of the brain, because of its greater lability, is probably nucleoprotein a (McGregor, '17). One would expect it to be associated with the vital functions. It probably is a combination of the globulin a, globulin b, and the nucleoprotein of an earlier worker (Halliburton, '94). Nucleoprotein b is mUch more stable and may be the protein of the chromatin and Nissl bodies, thus related to the hereditary quality of the nerve cell. Neurokeratin is stable and probably is connected with the structure of the nerve sheaths. It is highly important to know how these different proteins increase with growth, but we have only indirect evidence of what these changes are. From the data on total protein, protein phosphorus and protein sulphur (table 11), we can get an idea, of what is happening, however, Thus indirectly we can suggest that neurokeratin approaches a maximum percentage at two years of age, but is present in very small amounts in even early fetal life. Nucleoprotein b is probably present in largest percentage amounts inearly fetal life, but continues to increase in absolute amounts (table 12) until maturity, when there is about twice as much as of nucleoprotein a and half as much as of neurokeratin (McGregor, '17). Nucleoprotein a possibly is always present, but probably is largest in percentage amounts when nerve growth and activity are greatest. It would not do even to guess how these last two proteins are distributed in the brain.
The total protein curve (fig. 1) indicates that some particular protein (possibly nucleoprotein b) is an especially important factor in the subsequent growth of the brain. It seems to lead in the increases that take place.
Extractives
The separation of extractives into organic and inorganic, as given in the data, is of but little value because of the fact that such a separation, based on the solubility of organic constituents in alcohol and the insolubility of the inorganic ones in alcohol (or on the residue after ignition), is very unreliable. The data given are merely suggestive. Howev-er, the determination of total extractives is rather accurate. Inosit, urea, leucin, tyrosin, taurin, hjTDOxanthin, and peptones are a few of the organic substances present in this fraction. In general it may be stated that the larger the percentage of these simpler crystalloidal molecules, the more rapid the metabolism and the younger the tissue. Various inorganic salts of sodium, potassium, ammonia, calcium, magnesia, and iron have about the same significance. While the rate of growth is high, these constituents are present in larger percentage amounts (table 11), but with a decrease in rate of development they rapidly decrease in rate of formation, until after two years of age they are but very slowly increased in absolute amount (table 12).
They are present in larger amounts in cells than in axis cylinders. Potassium salts and chlorides are supposed to be related to nerve conductivity (Alcock and Lynch, '11).
In drawing conclusions concerning the rate of activity of nerve tissue from the percentage amounts of extractives, one needs to remember that it may be more accurate to leave the sheath substances out of the reckoning. The calculations would then be based on the assumption that but three-fifths of total solids are directly concerned.
Sulphur compounds
By estimating sulphur in the various fractions we obtain information about the relative amounts of several important brain compounds. The lipin sulphur is a measure of the amount of sulphatid, and is therefore largely concerned in sheath development. In consequence it obtains a maximum rate of formation at about three months of age. Protein sulphur represents the amount of cystin in protein combination. Cystin is present in much smaller amounts in the nucleoproteins of the brain than in neurokeratin. So protein sulphur gives us a rough estimate of the amounts of neurokeratin being formed. It will be noticed that this form of sulphur follows very closely myelin formation (table 10). Neutral sulphur may represent an intermediate oxidation product of cystin or possibly taurin; an increase in this form might indicate a decreased oxidative ability in the cells (W. and M. L. Koch, '13). Of the total sulphur, neutral sulphur forms a greater portion in the younger tissue, while the portion of protein sulphur increases with age. The inorganic sulphates are the final sulphur oxidation products. They remain rather constant in percentage amounts (table 11). This may be due to the fact that, they are readily eliminated from the cell. Total sulphur increases in percentage of fresh tissue until adult age, then remains rather constant. The maximum addition, of about 3 mg. per day, takes place at about three months of age (table 13).
Phosphorus compounds
The amount of phosphorus in the lipins is used to determine the amount of the phospho-lipins. It is added most rapidly at birth (table 13, fig. 2) (at least 3.5 mg. per day), but like most of the other constituents, its rate of addition per unit of reaction substances is greatest in the youngest tissue (tables 14 and 15, fig. 3).
Percentage Increase Per Day
Fig. 3
28
32
36
Protein phosphorus represents the amount of nucleoprotein. This probably closely approximates the changes in the activity of the protoplasm, both nucleus and cytoplasm. This form increases in amount with age, but the percentage changes less than any other kind.
Under the heading of organic phosphorus is included a number of comparatively simple compounds of phosphorus with organic radicles. There is no definite separation of this group from the following one (Emmett and Grindley, '06). It is representative of the amount of protein metabolism and bears a definite relation to the two colloidal forms of phosphorus mentioned above.
Inorganic phosphates are also a measure of rate of activity. In fact, the sum of these last two forms the best criterion of rate of phosphorus metabolism. It is worth noticing that in terms of percentage of total phosphorus the amounts of colloidal phosphorus compounds are increasing with growth, while those of the crystalloidal forms are decreasing (table 11). In fresh tissue the percentage of extractive phosphorus increases slightly, then decreases to a certain extent; but these small variations from a constant may not be significant. The figures, however, indicate rather definitely that these simpler forms of phosphorus do not closely follow the change in percentage of water, as one would expect if the quantity of fluid determined the amount of extractives. From table 11 it is evident that extractive phosphorus, like other extractives, markedly decreases in the percentage of total solids.
Comparison of forebrain, cerebellum, and brain stem
In the adult brain the cerebellum contains the largest percentage of water, the forebrain slightly less, the brain stem least. A high percentage of solids indicates slower but more highly dfferentiated metabolism; therefore the cerebellum acts fastest, while the brain stem is most stereotyped. During growth the rate of increase in the percentage of solids is in the following order, brain stem (table 4), forebrain (table 1), and cerebellum (table 7) ; this is, of course, to be expected.
In the stem the phosphatids are in larger amounts (table 5) and are probably laid down earlier than in the other two divisions of the brain. The cerebellum contains the smallest amount of this group of constituents (table 8) , indicating that it is probably less highly specialized than other parts.
The cerebrosides and sulphatids are present in slightly larger amounts in the stem (table 5) than in the forebrain (table 2), but in very much larger quantities than in the cerebellum (table 8). This would indicate that one of the main differences in chemical constitution between the cerebellum and the rest of the brain is in the amount of meduUation.
Cholesterol, etc., is found most largely in the stem and least in the cerebellum.
The total lipins are not only largest in amount in the stem (table 5) and least in the cerebellum (table 8), but possibly are formed slightly earlier and at a more rapid rate in the same order.
In all divisions the proteins show in general variations exactly opposite to that of the lipins. Thus with age there is a decrease in percentage of solids (tables 2, 5, and 8). The total proteins exist in but slightly different percentages in the different parts of the fresh tissue (tables 1, 4, and 7), and they seem to be formed at approximately the same rate in all.
In an attempt further to analyze the meaning of these variations in protein content, the data frpm protein sulphur and protein phosphorus are of value. It is probable that the greater amount of protein -sulphur is in neurokeratin, a constituent of supporting tissue, while the protein phosphorus is very largely present as nucleoprotein b (0.6 per cent P), only a relatively small amount being present as nucleoprotein a (0.11 percent P). (The percentage amount of the former, 10 per cent, is about twice that of the latter, 5 per cent in adult tissue.) From tables 1, 4, skid 7, then, it will be noticed that there is more than twice as much nucleoprotein in the cerebellum as in other parts of the brain. This difference prevails throughout growth. The stem and forebrain differ but little in this respect. On the other hand, protein sulphur (neurokeratin) is a little greater in the brain stem than in the forebrain or cerebellum. To judge from these data, one might state that the number of nuclei, or at least the amount of nuclear material, is considerably larger in the cerebellum, while the amount of supporting tissue is not very different in the various parts of the brain. Concerning the extra nuclear proteins (nucleoprotein a) it is difficult to make more than a guess — that they would vary with the other functioning protein (nucleoprotein h).
Neutral sulphur is a rough measure of the amount of protein metabolism taking place. It is rather striking that the greatest rate of protein metabohsm is in the forebrain (table 2) and cerebellum (table 8) and least in the brain stem (table 5). The rate in all remains rather constant in spite of the fact that the amount of protein increases with age.
Throughout growth the total extractives are present in much larger amounts in the cerebellum (table 8) than in the rest of the brain. The stem has a slightly larger percentage than the forebrain. In all divisions the maximum addition per day is reached at about three months of age (tables 2, 5, and 8, fig. 2). After this there is a slow decrease in amount of daily additions till old age, indicating that aging is a regular decrease in rate of metabolism. The larger part of the extractives in the cerebellum is composed of inorganic constituents. This is probably to be expected from the larger protein content in this division of the brain.
The total sulphur increases more rapidly and attains a somewhat greater percentage in the brain stem than in the forebrain (table 1) and a considerably greater percentage than in the cerebellum (table 7). This seems to be largely due to the relatively larger amounts of lipins in each division in the order named. The inorganic sulphates gradually increase in each division at about the same rate.
The amount of total phosphorus does not differ much in different parts of the brain, but the lipin phosphorus is greater in the stem (table 5) and forebrain (table 2) than in the cerebellum (table 8). The inorganic phosphates seem to be closely related to nucleoprotein h, because they are represented to a much greater extent in the cerebellum than in the other divisions of the brain.
General Discussion
1. Dominance of the nervous system
There seem to be no facts presented in this paper that are inconsistent with the theory that the chromosomes are very important in the early differentiation of cells. In fact, the data suggest that nucleoproteins (tables 10 and 11, fig. 1) then phosphatids and simple extractive molecules dominate in the youngest tissue. It is probable that there is a metabolic gradient in the fertilized cell that is important in determining which will be the head end of the organism (Child, '12). Very early in growth nervous tissue differentiates in this head region. Because of this early formation, much of the later development in other parts of the body is rather dependent on the nervous system. It needs to be emphasized that this dominance of one substance over another (or one organ over another) is but relative. Most of them are developing together, but their influence on each other is very different. Very probably growth consists in the formation of continually larger quantities of the respective cell constituents in a more or less definite order, commencing with the nucleoproteins (table 11, fig. 2) of the chromosomes. In the brain there is rapid formation of certain substances, then the presence and formation of the substances influence the rate of formation of another substance, this another, and so on till all have come into adjustment with the new conditions. While these changes are occurring in the brain, and partly because of them, other areas of differentiation are split off, which are to become other organs. Then in these areas a similar cycle of changes will occur. Probably each of the organs has periods of maximum growth. When such unusually large amounts of material are being formed rapidly, in comparison with the rate of formation at other periods of growth, we get an irregularity in the main curve of growth that produces a so-called growth cycle.
During growth substances are regularly coming to the various organs through the blood. We do not now believe that the amount of either these food substances or the oxygen determines the rate of growth, though they do influence it. The cells in any organ seem to grow somewhat in unison, but they are influenced by cells of other organs, both through the blood and through the nerves. There is no doubt that each organ directly influences the growth of every other in both of these ways. Certain glands secrete substances and discharge them into the circulation that have a disproportionately large effect in influencing growth in most tissues. But it is not correct to assume that growth is determined by these; it is only altered by them. Growth seems to be a general cell process, and these substances simply change the rate of this general cell development.
The growth of the brain is probably less under the influence of internal secretions than other organs. Indeed, there is strong evidence that the secretions are largely under the influence of the nervous system. There is no indication of internal secretions in simple organisms, yet these organisms have a similar form of growth.
2. Relation of these data to four physiological facts
In any interpretation of brain growth it is necessary to keep in mind several important facts:
1. A larger amount of early differentiation occurs in nervous tissue than in other tissues. Though this fact is associated with some definite differences that exist in the fertilized cell, the subsequent chemical supremacy is important in evolving the marked specialization. The early formation of colloidal substances such as the nucleoproteins, phosphatids, and sulphatids (table 10) give a peculiarity to young nerve tissue that permits it to influence rather markedly the development of other tissues. It is more than theoretical to assume that the early start of nervous tissue allows it to differentiate more than other parts of the body.
2. The nerve cells, unlike other cells, do not regenerate. It is very probable that a nerve cell if tested for regenerative power early enough in its growth would regenerate just as other undifferentiated tissues do. It very soon reaches a stage, however, w^hen it is so highly specialized by the elaboration of colloidal complexes (table 11) that regeneration is impossible.
3. The number of nerve cells remains constant. Rather early in growth, probably as early as the seventh fetal month (table 10) the number of nerve cells is largely determined. No amount of functioning produces an increase. This would indicate that the chemical changes in brain growth are fixed within rather close limits. It also suggests that development in the brain is essentially different than elsewhere. Probably the main processes are determined at the time of the formation of the cells. The organization is such, however, that smaller but no less important (speaking physiologically) change occurs during later activity.
4. Nervous tissues remain constant in composition under conditions that markedly alter many other tissues. The chemical composition of the nervous system must be related to this supremacy. The large amounts of several of the lipins (table 10) seem to be of importance. Though the large amount of colloidal material in the form of lipins and proteins is often supposed to be indicative of slower metabolism and a lack of dominance (Child, '11), the chemical condition in the brain would suggest that colloidal structure is equally important wdth the rate of metabolism in maintaining dominance. It te conceivable that in the case of the brain its early importance, due to the high rate of metabolism, should be maintained through specialized activity, even when this rate is no longer greater than the rate in other tissues. The highly specialized nerve fiber and cell are made of many compounds that are but slightly available to other tissues, because such substances are in almost irreversible equilibrium with metabolizing substances elsewhere.
Another factor that is undoubtedly involved is the selective nature of the membranes surrounding the cells of the nervous system. Very probably such membranes or surfaces are much more common than is supposed, thus providing means of keeping the various tissues in equilibrium with each other. If the membranes in the nervous system are more nearly irreversible than in other parts, the condition exists that is favorable for maintenance under circumstances that use up other tissues.
No other tissue has a chance to supplant the nervous system with its highly specialized pathways to all parts of the body.
It does not need to depend on its rate of activity for supremacy; the conditions it has developed for its maintenance assure this dominance though the means used for obtaining it no longer exist.
3. Concerning three periods of growth
There are three distinct processes to be distinguished in brain development. The one that takes place first is cell division. This is probably almost completed at the time of the sevenmonth-old fetus. It is worth noting that there is no evidence of sheath development up to this point. There are no cerebrosides; the amounts of sulphatids are increasing slowly. The phosphatids do not show any dominance. The relatively large amounts of protein, and especially the nucleoproteins, suggest that chromosome formation is very prominent. The large quantity of extractives emphasizes the fact that metabolism is very rapid during this period.
From the seven-month fetus to about the time of birth, cell growth is the important process. At this time the phosphatids come into prominence, while the proteins and extractives retain their earlier dominance. Cholesterol, though present, is not important. The same is true of sulphatids, while the cerebrosides are lacking entirely or are present in but small amounts. These changes arfe what one would expect in growing cells and enlarging axis cylinders. How important the axis cylinders are in accounting for brain growth is indicated by the fact that about two-fifths of the brain consists of them.
The third period is that of meduUation. It becomes prominent soon after birth, reaches its maximum a few months after birth, and slowly decreases in importance. The sheaths comprise about two-fifths of the brain substance, so it is not surprising that cerebrosides, sulphatids, and some of the phosphatids become so prominent. The proteins and extractives are skill of importance, but thoroughly masked by the new process. It is probable that when the nerve cells reach the stage at which conditions are proper for sheath formation, there is a release of energy or an alteration in metabolism through the extension of the field of local dominance that is large enough to amount to a slowing down temporarily of the rate of loss of growth power.
By comparing these results with those obtained in a growth series on the brain of the albino rat (W. and M, L. Koch, '13) a great similarity is evident. The nature of the process, the division into periods, the relative amounts of the various constituents, and their order of development are much alike. The main differences are found in the larger percentage amounts of lipins, with a corresponding decrease in proteins and a great lengthening of the periods of growth. Thus the changes occurring in the rat brain are much more rapid than in human brain, but the rat brain does not attain quite the same degree of differentiation. By comparing the data in the two series for extractives as a whole, and the various extractives, no marked differences are evident, indicating that the changes in rate of metabolism with growth are similar in both, though the time necessary to change from one corresponding physiological age to another in the rat is probably but about one-thirtieth of that in the human.
4. Nature of the growth process
One of the most interesting points which these data raise is that of the nature of the growth process in nervous tissue. The curves show that the brain as a whole, as well as each of the individual substances or groups of substances (tables 12 and 13, figs. 1 and 2) estimated, increases slowly in absolute amounts per unit of time during the first part of development. Later the increase is larger, and is then followed by a period when the amounts are continually smaller. If, however, one observes the curve for the amount added per unit mass of substance during a given period of time (tables 14 and 15, fig. 3) it is seen that the rate of addition is greatest in the youngest tissue. This rate of addition diminishes most at first, then more slowly, and is followed by a somewhat greater comparative rate of loss of growth power. The first curves (absolute amounts) are smilar to those reported for growth of the whole organism (Robertson, '08). Such curves are by some authors supposed to indicate that the process they represent is an autocatalytic one (a chemical reaction that increases in speed at first because of the catalj^zing effect of a product of the reaction, and then slows down, because of the retarding effect of larger amounts of a product of the reaction and decrease in the original substance). Can the second curve, however, be reconciled with this theory? From this curve it would seem that the rate of reaction is fastest at first and slows down continuously during growth (Meyer, '14).
There is no inconsistency between these two facts (1st, that the absolute amount of substance added is greatest during the middle period of development; 2d, that the amount of substance added per unit mass is greatest at an early period of development) if we make certain assumptions. It is necessary to assume that all or nearly all of the substance (or group of substances, or total brain, or total organism) is a product of this reaction or determined by some other reaction. The substances .weighed are entirely (within limits of error in data) the product of something not weighed or too small to make a significant difference in the weighing. This means that the cytoplasm, and probably nucleus (Loeb, '06), is a product of something else either present and very small, or absent, or not weighable. The easiest interpretation of this difficulty is to invoke the aid of vitalism. This would furnish our unweighable element that determines the growth of even the protoplasm. However, if something a little more substantial is required, one can assume the presence in the brain (or in some other part of the body connected physiologically with the brain) of a very small amount of a substance that in some way determines the formation of all other substances in the tissue (or organism) considered. This substance probably would decrease during growth. One or more of its products would catalyze its effect on formation of other substances. It might exert its control over other reactions by operating over a longer period of time or by having an unusual nature. It is conceivable that a hormone or enzyme-like compound might have such unlimited power. This would assume that at fertilization, or soon after, this substance was made, and that subsequent development is essentially a product of it. Aging would mean the using up of this substance or an interference with its rate of reaction. Any variations in growth would be due to alterations in the general growth produced by other substances or conditions.
Though the hormones and the active principles in the internal secretions are very popular these days, it seems rather too much to expect that one and only one of them possesses such vitalistic properties. It seems more rational to suppose that they are active in bringing about alterations in growth, but that the main process is independent of them. There is practically no evidence that such substances are determiners of growth in unicellular organisms. If one accepts the autocatalytic theory, it seems necessary to give up the protoplasmic theory, for protoplasm, too, should be simply a product and does not possess growing power. As a result of this and other work, it can be stated with considerable certainty that neither nucleus nor cytoplasm causes growth to take place autocatalyticaUy, If one believes that the evidence for the living, growing nature of the protoplasm as a whole is well founded, chemical autocatalysis should be discarded. The data agree so well with the theory, however, that there must be some reason why a substance in a living organism, as well as the whole tissue or organism should add largest absolute amounts of substance (table 13, fig. 2) during the middle of the growth period. It is worthy of mention, though it is probably not a fundamental explanation to say that protoplasm has an inherent power, when unimpeded by the lack of food or too much of the products of its activity, to increase in a geometrical ratio. As is well known, bacteria and unicellular organisms increase in number and in absolute weight (when retarding factors are small) in this 1, 2, 4, 8, 16 ratio. If such numbers are plotted against tune, the first part of the S-shaped curve is obtained. The latter half of the curve is produced through decreasing the geometrical ratio by the retarding effect of lack of food or production of toxic products. By analogy, such a curve should be produced in a multicellular organism, through the division and development of the cells producing it. It is thus seen that the essential characteristics of autocatalysis are the necessary result of cell division in an imperfect environment. Of course, one of the reasons why cells do not divide so often when there are more of them in a more unfavorable medium is that the individual cells do not grow to the dividing stage so quickly. However, one can apply the geometrical ratio idea to the development of the individual cell if that is found to increase in absolute weight fastest during the middle period of growth. In fact, it is rather to be expected that such would be the form of its growth, without its being in any way related to autocatalysis. For if the protoplasm formed on cell division is thought of as a unit of protoplasm, it would form two units in a certain period of time; then these two would form four, and so on through the geometrical series, if no retarding factors were present. But there are undoubtedly such factors, so we get essentially the autocatalytic phenomenon. The size of the cell, the relation of size of the nucleus to that of the cytoplasm, the amount of cell differentiation, complexity of colloidal substratum of cell are large factors in determining this form of growth. There seems to be a physiological state that is rather definite for any kind of cell, which, unaltered, tends to make the cells increase. One sees the necessity, granting the power of protoplasm to produce more material like itself, in an increasingly unfavorable environment, for the S-shaped curve of growth. This is independent of the question why growth takes place; it is true, irrespective of the nature of the growth impulse. It is probably not wise, however, to speak of such growth as autocatalytic, because it probably does not have a chemical autocatalytic basis. Though enzymes seem to play a part in it, it is not necessarily enzymic at all, much less autocatalytic and monomolecular. Probably anything that can increase geometrically, put under progressively less favorable conditions, whether living or not (say, the growth of a crystal in a slightly supersaturated solution), would give an autocatalytic form of increase.
Summary
1. During growth the proteins, phosphatids, sulphatids, cerebrosides, cholesterol, and total solids increase in percentage amounts. There is but slight change in the percentage of extractives, either organic or inorganic. Water decreases regularly to maturity.
2. In percentage of solids each of the lipins increases rapidly until a few months after birth, then more slowly until maturity. (Cerebrosides are not present in free condition till about the time of birth.) The proteins slowly decrease in percentage of solids with growth, but the extractives, both organic and inorganic, very rapidly decrease.
3. At birth most of the brain compounds are being laid down most rapidly. Cerebrosides and sulphatids, however, have the greatest daily additions about three months after birth.
The following amounts, in milligrams, are added per day in a new-born child: water 3270, solids 494, lipins 165, phosphatide 85, cholesterol + 70, sulphatids 7.7, cerebrosides 1.9, proteins 186, organic extractives 100, inorganic extractives 44, sulphur 2.3, phosphorus 8.5.
4. The brain stem contains the largest percentage amounts of total solids, total lipins, and of each lipin, but the least protein, organic extractives, inorganic extractives, and water. The forebrain is not much different frQm the stem. The cerebellum, however, varies largely. In development, the brain stem differentiates chemically first and fastest. The forebrain follows closely. The cerebellum never attains to such a high degree of specialization.
The data may indicate that the cerebellum is not only the slowest and least meduUated, but that it remains the youngest division of the brain with the highest rate of metabolism.
5. It is suggested that, because of the early marked chemical differentiation of the brain in the head end of the organism, further development is greatly influenced by the central nervous system.
6. An attempt is made to correlate the data obtained with the early differentiation of specialized nerve tissue and its constancy in number of cells and composition.
. 7. The chemical analyses agree that brain growth consists of 1) increase in the number of cells; 2) their growth, including that of the axis cylinders, and 3) medullation.
8. The data show that, though the absolute amount of each of the constituents added is greatest during a middle period of growth (birth), the greatest rate of growth is in the youngest tissue. It is not believed that brain growth is necessarily autocatalytic. The whole brain, as well as each constituent, increases with development, as is to be expected if it is assumed that a given mass of protoplasm makes more material like itself in an increasingly less favorable environment. It seems to be a logical necessity, not even dependent upon life.
Literature Cited
Alcock, N. H., and Lynch, G. Roche. 1911 On the relation between the physical, chemical, and electrical properties of the nerves. III. Total ash, sulfates, phosphates. J. Physiol., vol. 39, p. 402.
Child, C. M. 1911 A study of senescence and rejuvenescence based on experiments with Planaria dorotocephala. Arch. Entw. Mech. Org., vol. 31, p. 571.
1912 Studies on the dynamics of morphogenesis and inheritance in experimental reproduction. IV. Certain dynamic factors in the regulatory morphogenesis of Planaria dorotocephala in relation to the axial gradient. Jour. Exp. Zool., vol. 13, p. 103.
CowDRY, E. V. 1914 The comparative distribution of mitochondria in spinal ganglia cells of vertebrates. Am. Jour. Anat., vol. 17, p. 1.
Donaldson, H. H. 1916 A preliminary determination of the part played by myelin in reducing the water content of the mammalian nervous system (albino rat). Jour. Comp. Neur., vol. 26, p. 443.
Emmett, M. D., and Grindley, H. S. 1906 The chemistry of flesh (third paper). A study of the phosphorus content of flesh. J. Am. Chem. Soc, vol. 28, p. 25.
Halliburton, W. D. 1894 The proteids of nervous tissues. J. Physiol., vol. 15, p. 90.
Koch, M. L. 1913 Contributions to the chemical differentiation of the central nervous system. I. A comparison of the brain of the albino rat at birth with that of the fetal pig. J. Biol. Chem., vol. 14, p. 267.
Koch, W. 1910 Zur Kenntnis der Schwefelverbindungen des Nerven Systems. II. Uber ein Sulfatid aus nerven Substance. Z. Physiol. Chem., vol. 70, p. 94.
Koch, W., and Koch, M. L. 1913 Contributions to the chemical differentiation of the central nervous system. III. The chemical differentiation of the brain of the albino rat during growth. J. Biol. Chem., vol. 15, p. 423.
Koch, W., and Mann, S. A. 1907-08 A comparison of the chemical composition of three human brains at different ages. Am. J. Physiol., vol. 36, p. xxxvi.
Levene, p. a., and Jacobs, W. A. 1912 On sphingosine. J. Biol. Chem., vol. 11, p. 548.
LoEB, J. 1906 Weitere Beobachtungen iiber den Einfluss der Befruchtung und der Zahl der Zelkerne auf die Saurebildung im Ei. Biochem. Z., vol. 2, p. 34.
MAcARTHtfR, C. G- 1914 Brain cephalin: I. Distribution of the nitrogenous hydrolysis products of cephalin. J. Am. Chem. Soc, vol. 36, p. 2397.
MacArthur, C. G., and Darrah, J. E. 1916 Nitrogenous constituents of brain lecithin. J. Am. Chem. Soc, vol. 38, p. 922.
MacArthur, C. G., and Jones, O. C. 1917 Some factors influencing the respiration of ground nervous tissue. J. Biol. Chem., vol. 32, p. 259.
McGregor, H. H. 1917 Proteins of the central nervous system. J. Biol. Chem., vol. 28, p. 403.
Meyer, A. W. 1914 Curves of prenatal growth and autocatalysis. Arch. Entw. Mech. Org., vol. 40, p. 497.
Robertson, T. B. 1908 On the normal rate of growth of an individual and its biochemical significance. Arch. Entw. Mech. Org., vol. 25, 581.
Rosenheim, O. 1913 The galactosides of the brain. I. Biochem. J., vol. 7, p. 604.
SiGNORELLi, E. 1910 Tiber die Oxydation-processe der Lipoide des Riicken marks. Biochem. Z., vol. 29, p. 25.
Smith, J. Lorrain, and Mair, W. 1912-13 The development of lipoids in the brain of the puppy. J. Path. Bact., vol. 17, p. 123. The lipoids of the white and gray matter of the human brain at different ages. J. Path. Bact., vol. 17, p. 418.
TABLE 1
Forebrain: Constituents in -percentage of fresh tissue
FETUS
3
MONTHS
(13)1
FETUS
7
MONTHS
(12) =
CHILD
1
MONTH
(11)
CHILD
3
MONTHS
(V)
CHILD
8
MONTHS
(4)3
ADULT
21 YEARS
(23)
ADULT
(33)
YEARS
(28)
ADULT
35 YEARS
(3)
ADULT
67 YEARS
(22)
Water
91.91 8.09
1.04
0.16 0.58
90.56 9.44
1.24
0.27 0.97
88.09 11.91
1.94
0.25 1.53
87.03 12.97
(1.74)4 .30 .50 1.70
85.81 14.19
3.17 0.49 0.50 0.91
77.32
22.68
5.68 1.29 1.84 3.63
77.06 22.94
6.00
1.28 0.66
4.81
72.85 27.15
6.86 2.58 1.72 4.08
78.47
Solids
21.53
Phosphatids
Cerebrosides
Sulphatids
Cholesterol
6.54 1.72 1.35 2.55
Total lipins
1.78
2.48
3.71
4.24
5.06
12.44
12.75
15.23
12.15
Total proteins
Organic extractives
Inorganic extractives
3.77
1.54 1.00
3.98
1.77 1.21
4.57
2.44 1.19
5.29
2.38 1.06
6.09
2.01 1.03
8.03
1.19 1.02
8.11
1.11 0.96
8.99
2.03 0.91
7.53
0.88 0.96
Total extractives. .
2.54
2.98
3.63
3.44
3.04
2.21
2.07
2.94
1.84
Lipin suiphur... . Protein sulphur. Neutral sulphur. Inorganic sulphur
0.003 0.026 0.015
0.001
0.005 0.028 0.018
0.002
0.005 0.033 0.022
0.004
0,010 0.038 0.026
0.005
0.010 0.069 0.018
0.012
0.036 0.053 0.013
0.002
0.013 0.052 0.007
0.003
0.034 0.039 0.022
0.009
0.027 0.061 0.015
0.003
Total sulphur
0.045
0.053
0.064
0.079
0.109
0.104
0.075
0.104
0.106
Lipin phosphorus
Protein phosphorus ,
Organic phosphorus
Inorganic phosphorus
0.044 0.025 0.026 0.056
0.054 0.009 0.028 0.062
0.080 0.005 0.036 0.082
0.078 0.006 0.055 0.074
0.127 0.008 0.032 0.055
0.256 0.013 0.012 0.058
0.284 0.011 0.027 0.091
0.300 ,0.014 0.049 0.048
0.254 0.012 0.008 0.053
Total phosphorus..
0.151
0.153
0.203
0.213
0.222
0.339
0.363
0.411
0.327
1 The two brains of this age that were used for this analysis were not separated into cerebellum, forebrain, and stem, because the brains were too small to make good samples of these divisions. For purposes of comparison the whole brain was arbitrarily divided into cerebellum 10 per cent, brain stem 10 per cent, and forebrain 80 per cent.
2 The same is true of this brain.
3 See section on limitations.
4 See section on limitations for explanation of this low figure.
TABLE 2 Forebrain: Constituents in percentage of solids
FETDS
FETUS
CHILD
CHILD
CHILD
ADULT
ADULT
ADULT 35 YEARS
ADULT
3
7
1
3
8
21
33
67
MONTHS
MONTHS
MONTH
MONTHS
MONTHS
TEARS
YEARS
YE.\.RS
(13)1
(12)1
(11)
(V)
(4)1
(23)
(28)
(3)
(19)
(22)
Phosphatids. .
12.90
13.12
16.27
(13.40)1
22.33
25.06
24.67
25.26
25.34
27.19
Cerebrosides..
2.32
3.43
5.67
5.59
9.50
7.13
8.00
Sulphatids ....
1.95
2.85
2.06
3.87
3.53
8.12
2.89
6.32
6.90
6.26
Cholesterol. . .
7.24
10.28
12.86
13.09
6.39
16.02
22.45
15.01
18.47
15.03
Total lipins
22.09
26.25
31.19
32.68
35.68
54.87
55.60
56.09
57.84
56.48
Total proteins . .
46.56
42.15
38.31
40.78
42.91
35.40
35.36
33.10
32.27
34.97
Organic ex
tractives
19.04
18.75
20.52
18.35
14.18
5.23
4.85
7.46
6.12
4.08
Inorganic ex
tractives —
12.31
12.85
9.98
8.19
7.23
4.50
4.19
3.35
3.77
4.47
Total extrac
•
tives
31.35
31.60
30.50
26.54
21.41
9.73
9.04
10.81
9.89
8.55
Lipin sulphur.
0.039
0.057
0.041
0.077
0.071
0.163
0.058
0.127
0.138
0.125
Protein sul
phur
0.314
0.294
0.277
0.^7
0.483
0.235
0.225
0.146
0.279
0.279
Neutral sul
phur
0.187
0.183
0.190
0.195
0.128
0.057
0.029
0.081
0.022
0.070
Inorganic
sulphur
0.013
0.022
0.038
0.037
0.085
0.011
0.015
0.032
0.029
0.015
Total sulphur...
0.553
0.556
0.546
0.596
0.767
0.466
0.327
0.386
0.468
0.489
Lipin phos
phorus
0.538
0.563
0.676
0.597
0.886
1.136
1.017
1.110
1.120
1.179
Protein phos
phorus
0.306
0.100
0.041
0.045
0.056
0.055
0.048
0.052
0.063
0.057
Organic phos
phorus
0.322
0.300
0.306
0.422
0.225
0.053
0.117
0.180
0.226
0.035
Inorganic
phosphorus .
0.678
0.648
0.693
0.565
0.384
0.258
0.394
0.172
0.189
0.244
Total phos
phorus
1.844
1.611
1.716
1.629
1.551
1.502
1.576
1.515
1.598
1.515
iSee table 1.
TABLE 3
Forebrain: Weights of constituents in grams
FETUS
FETUS
CHILD
CHILD
CHILD
ADULT
ADULT
ADULT
ADULT
3
7
1
3
8
21
33
35
67
MONTHS
MONTHS
MONTH
MONTHS
MONTHS
TEARS
YEARS
YEARS
YEARS
(13)1
(12)1
(11)
(7)
(4)1
(23)
(28)
(3)
(22)
Brain
17.08
119.0
457.4
585.2
492.5
1122.4
1221.3
1158.3
1297.9
Forebrain..
13.664
95.2
395.0
514.0
409.0
950.0
1026.0
986.0
1075.0
Water
12.56
86.16
347.9
447.3
351.0
734.5
790.7
718.3
843.6
Solids
1.104
9.04
47.1
66.68
58.0
215.5
235.3
267.7
231.5
Phospha
tids —
0.1424
1 . 1808
7.660
8.940
12.96
53.95
61.56
67.64
70.33
Cerebro
sides...
0.0000
0.0000
0.000
1.542
2.00
12.26
13.13
25.44
18.49
Sulfa
tids....
0.0216
0.2568
0.980
2.570
2.05
17.48
6.77
16.96
14.52
Choles
terol.. .
0.0792
0.9232
6.043
8.738
3.72
34.48
49.34
40.24
27.42
Total
lipins
0.2432
2.3608
14.660
21.80
20.69
118.1
130.80
150.28
130.60
Total pro
teins
0.5152
3.7888
18.05
27.19
24.91
76.28
83.20
88.65
80.97
Organic
extrac
tives . .
0.2104
1.6848
9.638
12.24
8.22
11.31
11.39
20.02
9.46
Inor
ganic
extrac
tives...
0.1368
1.152
4.700
5.45
4.21
9.69
9.85
8.97
10.32
Total ex
tractives
0.3472
2.8368
14.338
17.69
12.43
21.00
21.24
28.99
19.78
Lipin
sul
phur. . .
0.0004
0.0048
0.020
0.051
0.041
0.342
0.133
0.335
0.290
Protein
sul
phur.. .
0.0035
0.0266
0.130
0.195
0.282
0.504
0.533
0.385
0.656
Neutral
sul
phur.. .
0.0021
0.0171
0.187
0.134
0.074
0.123
0.072
0.217
0.161
Inor
ganic
sul
phur...
0.0002
0.0019
0.016
0.026
0.048
0.019
0.031
0.088
0.032
Total sul
phur
0.0062
0.0505
0.253
0.406
0.446
0.988
0.770
1.025
1.140
473
TABLE 3— Concluded
FETUS
3
MONTHS
(13)'
FETUS
7
MONTHS
(12)1
CHILD
1 MONTH
(11)
CHILD
3
MONTHS
(7)
CHILD
8
MONTHS
(4)'
ADULT
21 YEARS
(23)
ADULT
33
YEARS
(28)
ADULT
35 TEARS
(3)
ADULT
(67)
YEARS
(22)
Lipin phosphorus
0.0060
0.0514
0.316
0.401
0.519
2.432
2.401
2.958
2.731
Protein
.
phosphorus
0.0034
0.0086
0.020
0.031
0.033
0.124
0.113
0.138
0.129
Organic phosphorus
0.0025
0.0266
0.142
0.283
0.131
0.114
0.277
0.483
0.086
Inor
ganic phosphorus
0.0077
0.0590
0.324
0.380
0.225
0.551
0.934
0.473
0.570
1
Total phosphorus
0.0206
0.1457
0.802
1.095
0.908
3.221
3.724
4.052
3.516
^ See table 1.
TABLE
Brain stem: Constituents in percentages of solids
FETUS
3
MONTHS (13)1
FETUS
7
MONTHS
(12)1
CHILD
1 MONTH
(14)2
CHILD
3
MONTHS
(20)
CHILD
8
MONTHS
(21)1
ADULT
21 YEARS
(27)
ADULT
35 TEARS
(18)
ADULT
67 YEARS
(26)
Phosphatids
Cerebrosides
Sulfatids
12.90 0.00 1.95 7.24
13.12 0.00
2.85 10.28
17.29 1.95 0.44
16.32
(25.86) 1.08 4.48
13.38
16.67 2.33 5.40
19.75
22.85
(0.81) 7.45 28.48
15.73
4.58
8.40
31.86
30.86 9.83 7.52
Cholesterol
11.87
Total lipins
22.09
26.25
36.00
44.80
44.15
59.59
60.57
60.08
Total proteins
46.56
19.04 12.31
42.15
18.75 12.85
39.21
17.31 7.66
40.55
8.61 6.04
40.52
9.50 5.83
31.41
5.45 3.55
29.96
5.78 3.69
32.01
Organic extractives. . . Inorganic extractives .
4.01 3.90
Total extractives
31.35
31.60
24.97
14.65
15.33
9.00
9.47
7.91
Lipin sulphur
Protein sulphur
Neutral sulphur
Inorganic sulphur
0.039 0.314 0.187 0.013
0.057 0.294 0.183 0.294
0.009
0.158 0.036
0.090 0.238 0.069 0.013
0.108 0.272 0.093 0.008
0.148 0.264 0.009 0.015
0.168 0.211 0.023 0.018
0.150 0.289 0.037 0.009
Total sulphur
0.553
0.556
0.410
0.481
0.436
0.420
0.485
Lipin phosphorus
Protein phosphorus. . . Organic phosphorus. . . Inorganic phosphorus.
0.538 0.306 0.322 0.678
0.563 0.100 0.300 0.648
0.674 0.138 0.252 0.595
1.100 0.068 0.119 0.435
0.753 0.064 0.168 0.425
1.035 0.041 0.064 0.314
0.778 0.052 0.184 0.199
1.343 0.044 0.147 0.238
Total phosphorus
1.844
1.611
1.659
1.722
1.410
1.454
1.213
1.772
1 See table 1. ^ gee table 4.
474
CHEMICAL CHANGES IN HUMAN BRAIN
475
TABLE 4 Brain stem: Constituents in percentage of fresh tissue
Water
Solids
Phosphatids
Cerebrosides
Sulfatids
Cholesterol
Total lipins
Total proteins
Organic extractives. . . Inorganic extractives .
Total extractives
Lipin sulphur
Protein sulphur
Neutral sulphur
Inorganic sulphur
Total sulphur
Lipin phosphorus
Protein phosphorus. . . Organic phosphorus. . . Inorganic phosphorus.
Total phosphorus
FETUS
3
MONTHS
(13)1
91.91 8.09
1.04 0.00 0.16 0.58
FETUS
7
MONTHS
(12)1
1.78
3.77
1.54 1.00
2.54
0.003 0.026 0.015 0.001
0.045
0.044 0.025 0.026 0.056
0.151
90.56 9.44
1.24 0.00 0.27 0.97
CHILD
1
MONTH
(14)2
2.48
3.98
1.77 1,21
2.98
0.005 0.028 0.018 0.002
0.053
0.054 0.009 0.028 0.062
0.153
86.15 13.85
2.40 0.27 0.06 2.26
4.99
5.43
2.37 1.06
3.43
0.001
0.022 0.005
0.094 0.019 0.035 0.083
0.231
CHILD
3
MONTHS
(20)
84.24 15.76
(4.07) 0.17 0.71 2.11
MONTHS
(21)'
7.06
6.40
1.35 0.95
2.30
0.014 0.037 0.011 0.002
0.064
0.172 0.011 0.019 0.068
0.270
82.71 17.29
2.89 0.40 0.94 3.41
7.65
7.01
1.64 1.00
2.64
0.019 0.047 0.016 0.002
0.084
0.131 0.011 0.029 0.074
0.245
ADULT
21 YEARS
(27)
73.60 70.34 26.40 29.66
ADULT
35
YEARS
(18)
ADUI/r
67
YEARS
(26)
6.03 (0.21) 1.97 7.52
15.73
8.29
1.44 0.94
2.38
0.039 0.069 0.002 0.004
0.114
0.273 0.011 0.017 0.083
0.384
4.69 1.36 2.49 9.43
17.97
8.90
1.71 1.10
2.81
0.050 0.062 0.007 0.005
0.124
0.231 0.015 0.055 0.059
0.360
76.26 23.74
7.33 2.33 1.78 2.83
14.27
7.60
0.95 0.93
1.88
0.036 0.069 0.009 0.002
0.116
0.317 0.011 0.035 0.058
0.421
1 See table 1.
2 Brain stem and cerebellum analyzed together, because of small sample.
476
C. G. MACARTHUR AND E. A. DOISY
TABLE 6 Brain stem: Weight of constituents in grams
FETtTS
FETUS
CHILD
CHILD
CHILD
ADULT
ADULT
ADULT
3 MONTHS
7 MONTHS
1 MONTH
3 MONTHS
8 MONTHS
21 YEARS
35 YEARS
67 YEARS
(13)>
(12)1
(14)2
(20)
(20)1
(21)
(18)
(26)
Brain
17.08
119.0
457.4
585.2
492.5
1122.4
1158.3
1297.9
Brain stem .
1.708
11.9
25.0
28.5
35.3
61.0
61.5
77.5
Water
1.57
10.77
21.54
24.00
29.20
44.90
43.26
59.10
Solids
0.138
1.125
3.46
4.50
6.10
16.10
18.24
18.40
Phospha
tids ....
0.0178
0.1476
0.600
1.160
1.024
3.678
2.884
5.681
Cerebro
sides . . .
0.0000
0.0000
0.068
0.048
0.141
0.128
0.836
1.806
Sulphatids
0.0027
0.0321
0.015
0.202
0.332
1.202
1.531
1.380
Choles
terol . . .
0.0099
0.1154
0.565
0.601
1.204
4.587
5.799
2.193
Total lipins.
0.0304
0.2951
1.248
2.012
2.700
9.595
11.052
11.059
Total pro
teins
0.0644
0.4736
1.358
1.814
2.475
5.057
5.474
5.890
Organic
extrac
tives... .
0.0263
0.2106
0.592
0.385
0.579
0.878
1.052
0.736
Inorganic
extrac
tives... .
0.0171
0.144
0.265
0.271
0.353
0.573
0.677
0.721
Total ex
tractives..
0.0434
0.3546
0.857
0.656
0.932
1.451
1.729
1.457
Lipin sul
phur
0.0001
0.0006
0.0003
0.0040
0.0138
0.0238
0.0308
0.0279
Protein
sulphur.
0.0004
0.0033
0.0105
0.0244
0.0421
0.0381
0.0535
Neutral
sulphur.
0.0003
0.0021
0.0055
0.0031
0.0007
0.0012
0.0043
0.0070
Inorganic
sulphur.
0.0000
0.0002
0.0013
0.0006
0.0014
0.0024
0.0031
0.0016
Total sul
phur
0.0008
0.0063
0.0182
0.0402
0.0695
0.0763
0.0900
CHEMICAL CHANGES IN HUMAN BRAIN
477
TABLE 6— Continued
FETUS 3 MONTHS
(13)'
FETUS
7 MONTHS
(12)1
CHILD 1 MONTH
(14)2
CHILD 3 MONTHS
(20)
CHILD
8 MONTHS
(21) J
ADULT 21 YEARS
(27)
ADULT 35 YEARS
(18)
ADULT 67 TEARS
(24)
Lipin
phosphorus..
0.0008
0.0064
0.0235
0.0490
0.0462
0.1665
0.1421
0.2457
Protein
phosphorus..
0.0004
0.0011
0.0048
0.0031
0.0039
0.0067
0.0092
0.0085
Organic
phosphorus..
0.0004
0.0033
0.0088
0.0054
0.0102
0.0104
0.0338
0.0271
Inorganic phosphorus..
0.0010
0.0074
0.0207
0.0194
0.0261
0.0506
0.0363
0.0450
Total phosphorus. . .
0.0026
0.0182
0.0578
0.0769
0.0865
0.2342
0.2214
0.3263
1 See table 1.
2 See table 4.
TABLE 7 Cerebellwn. Constituents in percentage of fresh tissue
FETUa 3 MONTHS
(12)1
FETUS 7 MONTHS
(12)1
CHILD 1 MOXTH
(14)2
CHILD 3 MONTHS
(17)
CHILD
S MONTHS
(1)'
ADULT 1 YEAR
(25)
ADULT 1 35 YEARS
(10)
ADULT 67 YEARS
(29)
Water
91.91 8.09
1.04 0.00 0,16 0.58
90.56 9.44
1.24 0.00 0.27 0.97
86.15 13.85
2.40
(0.27P (0.06)3 2.26
85.05 14.95
2.70 0.00 0.86 1.33
84.56 15.44
2.58 0.26 0.75 1.54
78.83 21.17
6.66 0.98 0.94 0.89
77.99 22.01
(2.84) 0.84 1.02 4.12
80.64
Solids
19.36
Phosphatids . . . Cerebrosides. . .
Sulphatids
Cholesterol ....
4.07 0.54 0.96 3.10
Total lipins
1.78
2.48
4.99
4.89
5.13
9.46
8.82
8.67
Total proteins . . .
Organic extractives
Inorganic extractives
3.77
1.54 1.00
3.98
1.77 1.21
5.43
2.37 1.06
6.97
1.90 1.19
6.94
2.10 1.28
8.95
1.55 1.23
8.60
(2.97) 1.61
7.66
1.68 1.36
Total extractives
2.54
2.98
3.43
3.09
3.38
2.78
(4.58)
3.04
Lipin sulphur. . Protein sulphur
0.003 0.026 0.015 0.001
0.005 0.028 0.018 0.002
0.001
0.022f 0.005
0.018 0.041 0.020 0.001
0.015 0.051 0.014 0.002
0.019 0.053 0.014 0.002
0.020 0.067 0.037 0.009
0.019 0.058
Neutral sulphur
0.006
Inorganic sulphur
0.002
Total sulphur
0.045
0.053
0.080
0.082
0.088
0.133
0.085
Lipin phosphorus
Protein phosphorus
Organic phosphorus
Inorganic phosphorus . .
0.044 0.025 0.026 0.056
0.054 0.009 0.028 0.062
0.094 0.019 0.035 0.083
0.122 0.045 0.020 0.075
0.115 0.046 0.039 0.086
0.278 0.042 0.022 0.110
0.140 0.036 0.080 0.114
0.178 0.028 (0.009) 0.106
Total phosphorus
0.151
0.153
0.231
0.262
0.286
0.452
0.370
0.321
1 See table 1.
2 See table 4.
' Earlier in the paper it was stated, that sulphur determinations were occasionally low. This is the case here. Because of the sugar content of sulphatids, if the latter is too low, these may be reported for cerebrosides when there are none free.
478
CHEMICAL CHANGES IN HUMAN BRAIN
479
TABLE 8
Cerebellum: Constituents in percentage of solids
FETUS
3
MONTHS
(13)'
FETUS
7
MONTHS
(12)1
CHILD
1 MONTH
(14) •i
CHILD
3
MONTHS
(17)
CHILD
8
MONTHS
(16)1
ADULT
21 YEARS
(25)
ADULT
35 YEARS
(10)
ADULT
67 YEARS
(29)
Phosphatids
Cerebrosides
Sulphatids
12.90 0.00 1.95 7.24
13.12 0.00
2.85 10.28
17.29
(1.95)3 (0.44)3 16.32
18.03 0.00 5.76
8.92
16.71 1.65 4.85 9.99
31.42 4.64 4.37 4.18
12.90 3.81 4.64
18.72
21.00
2.77 4 98
Cholesterol
16.05
Total lipins
22.09
26.25
36.00
32.71
33.20
44.61
40.07
44 70
Total proteins
Organic extractives . . . Inorganic extractives .
46.56
19.04 12.31
42.15
18.75 12.85
39.21
17.13 7.66
46.63
12.71 7.95
44.92
13.59 8.29
42.29
7.26
5.84
39.12
13.51 7.30
39.51
8.68 7.01
Total extractives
31.35
31.60
24.79
20.66
21.88
13.10
20.81
15.69
Lipin sulphur
0.039 0.314 0.187 0.013
0.051 0.294 0.183 0.022
0.009
0.158 0.036
0.115 0.273 0.129 0.009
0.097 0.323 0.092 0.015
0.088 0.252 0.064 0.007
0.093 0.307 0.168 0.044
100
Protein sulphur
Neutral Sulphur
Inorganic sulphur
0.296 0.032 0.009
Total sulphur
0.553
0.556
0.526
0.527
0.411
0.612
437
Lipin phosphorus
Protein phosphorus. . . Organic phosphorus. . . Inorganic phosphorus.
0.538 0.306 0.322 0.678
0.563 0.100 0.300 0.648
0.674 0.138 0.252 0.595
0.812 0.302 0.130 0.502
0.741 0.297 0.249 0.554
1.310 0.198 0.104 0.519
0.642 0.163 0.364 0.522
0.912 0.146 0.046 0.546
Total phosphorus
1.&44
1.611
1.659
1.746
1.841
2.131
1.691
1.650
1 See table 1.
2 See table 4. » See table 7.
480
C. G. MACARTHUR AND E. A. DOISY
TABLE 9 Cerebellimi: Weights of constituents in grams
FETUS
FETUS
CHILD
CHILD
CHILD
ADULT
ADULT
ADULT
3 MONTHS
7 MONTHS
1 MONTH
3 MONTHS
S MONTHS
21 TEARS
35 TEARS
67 TEARS
(13)'
(12)'
(14)2
(17)
(16)1
(25)
(10)
(29)
Brain
17.08
119.0
457.4
585.2
492.5
1122.4
1158.3
1297.9
Cerebellum .
1.708
11.9
37.4
42.6
48.2
111.4
110.8
145.4
Water
1.57
10.77
32.22
36.23
40.76
87.80
86.41
117.25
Solids
0.138
1.125
5.18
6.40
7.44
23.58
24.39
28.15
Phospha
tids
0.0178
0.1476
0.898
1.150
1.244
7.418
3.147
5.918
Cerebro
sides . . .
0.0000
0.000
0.101
0.000
0.125
1.091
0.931
0.785
Sulphatids
0.0027
0.0321
0.022
0.366
0.362
1.036
1.130
1.396
Choles
terol . . .
0.0099
0.1154
0.845
0.567
0.742
0.991
4.565
4.507
Total lipins.
0.0304
0.2951
1.866
2.084
2.473
10.536
9.772
12.606
Total pro
teins
0.0644
0.4736
2.031
2.969
3.345
9.968
9.529
11.138
Organic
extrac
tives . . .
0.0263
0.2106
0.886
0.810
1.012
1.704
3.291
2.443
Inorganic
extrac
tives... .
0.0171
0.144
0.397
0.507
0.617
1.370
1.784
1.977
Total ex
tractives..
0.0434
0.3546
1.283
1.317
1.629
3.074
5.075
4.420
Lipin sul
phur . . .
0.0001
0.0006
0.0004
0.0077
0.0072
0.0212
0.0222
0.0276
Protein
sulphur.
0.0004
0,0033
0.0175
0.0246
0.0590
0.0742
0.0843
Neutral
sulphur.
0.0003
0.0021
0.0082
0.0085
0.0067
0.0156
0.0410
0.0087
Inorganic
sulphur.
0.0000
0.0002
0.0019
0.0004
0.0010
0.0022
0.0100
0.0029
Total sul
phur
0.0008
0.0063
0.0341
0.0395
0.0980
0.1474
0.1236
1 See table 1.
2 See table 4.
TABLE 9— Continued
PETDS 3 MONTHS
(13)'
FETUS 9 MONTHS
(12)1
CHILD 1 MONTH
(14)2
CHILD 3 MONTHS
(17)
CHILD 8 MONTHS
(16)1
ADULT 21 YEARS
(25)
ADULT 35 YEARS
(10)
ADULT 67 YEARS
(29)
Lipin phosphorus .
0.0008
0.0064
0.0352
0.0520
0.0554
0.3097
0.1551
0.2588
Protein
phosphorus .
0.0004
0.0011
0,0071
0.0192
0.0222
0.0468
0.0399
0.0407
Organic phosphorus .
g.ooo4
0.0033
0.0131
0.0085
0.0188
0.0245
0.0886
0.0131
Inorganic phosphorus .
0.0010 0.0026
0.0074
0.0311
0.0320
0.0415
0.1225
0.1263
0.1541
Total phosphorus . . .
0.0182
0.08&4
0.1116
0.1378
0.5035
0.4100
0.4667
TABLE 10 Whole brain: Constituents in percentage of fresh tissue
FETUS
3
MONTHS
FETUS
7
MONTHS
CHILD
1 MONTH
CHILD
3
MONTHS
CHILD
8
MONTHS
ADULT
21 YEARS
ADULT
35 YEARS
ADULT
67 YEARS
Water
Solids
91.91 8.09
90.56 9.44
87.81
12.19
86.75 13.25
85.47 14.53
77.25 22.75
73.20 26.80
78.58 21.42
Phosphatids
Cerebrosides
Sulphatids
1.04
0.00
.16
.58
1.24
0.00
.27
.97
2.00 .04 .22
1.63
1.92 .27 .53
1.68
3.09 .46 .56
1.15
5.80 1.20 1.75 3.57
6.35 2.35 1.69 4.36
6.30 1.62 1.33
Cholesterol
2.62
Totallipins
1.78
2.48
3.89
4.42
5.26
12.32
14.75
11.87
Total proteins
3.77
1.54 1.00
3.98
1.77 1.21
4.69
2.43 1.18
5.47
2.29 1.08
6.24
1.99 1.05
8.14
1.24 1.04
8.95
2.10 0.99
7.54
Organic extractives
Inorganic extractives . . .
0.98 1.01
Total extractives
2.54
2.98
3.61
3.37
3.04
2.28
3.09
1.99
Lipin sulphur
0.003 0.026 0.015 0.001
0.005 0.028 0.018 0.002
0.004 0.029 0.022 0.004
0.011 0.038 0.026 0.005
0.012 0.066 0.016 0.010
0.035 0.054 0.013 0.002
0.034 0.043 0.023 0.009
0.026
Protein sulphur
0.061
Neutral sulphur
Inorganic sulphur
0.014 0.003
Total sulphur
0.045
0.053
0.059
0.080
0.104
0.104
0.109
0.104
Lipin phosphorus
Protein phosphorus
Organic phosphorus
Inorganic phosphorus. . .
0.044 0.025 0.026 0.056
0.054 0.009 0.028 0.062
0.081 0.007 0.035 0.082
0.086 0.009 0.051 0.074
0.124 0.012 0.032 0.060
0.259 0.016 0.013 0.064
0.280 0.016 0.052 0.055
0.248 0.014 0.010 0.059
Total phosphorus
0.151
0.153
0.205
0.220
0.228
0.352
0.403
0.331
TABLE 11 Whole brain: Constituents in percentage of solids
FETUS
3
MONTHS
Phosphatids
Cerebrosides
Sulphatids
Cholesterol
Total lipins
Total proteins
Organic extractives
Inorganic extractives . . .
Total extractives
Lipin sulphur
Protein sulphur
Neutral sulphur
Inorganic sulphur
Total sulphur
Lipin phosphorus
Protein phosphorus
Organic phosphorus
Inorganic phosphorus. . .
Total phosphorus
22.09
12.90 0.00 1.95 7.24
26.25
46.56
19.04 12.31
42.15
18.75 12.85
31.35
0.039 0,314 0.187 0.013
0.553
0.538 0.306 0.322 0.678
1.844
FETUS
7
MONTHS
13.12
0.00
2.85
10.28
31.90
38.46
19.93 9.68
31.60
0.057 0.294 0.183 0.022
0.556
0.563 0.100 0.300 0.648
CHILD 1
MONTH
16.40 0.33 1.80
13.37
33.30
41.30
17.29 8.15
29.61
0.033 0.238 0.180 0.033
0.184
0.664 0.057 0.287 0.672
1.611
1.680
CHILD 3
MONTHS
14.50 2.04 4.00
12.76
21.26 3.16 3.85 7.91
36.19
42.93
13.69
7.22
25.44
0.083 0.287 0.196 0.038
0.604
0.649 0.068 0.385 0.559
1.661
CHILD
8
MONTHS
25.52 5.28 7.70
15.70
54.20
35.82
5.46 4.58
20.91
0.083 0.454 0.110 0.068
0.715
0.853 0.083 0.220 0.413
1.569
ADULT
21 YEARS
23.69 8.77 6.30
16.26
55.01
33.38
7.83 3.69
10.04
0.154 0.238 0.057 0.009
0.458
1.140 0.070 0.057 0.282
1.549
ADULT
35
YEARS
29.42 7.56 6.21
12.24
55.43
11.52
0.127 0.160 0.086 0.034
0.407
1.044 0.060 0.194 0.205
1.503
ADULT
67 TEARS
35.21
4.58 4.72
9.30
0.121 0.285 0.065 0.014
0.485
1.158 0.065 0.047 0.276
1.546
CHEMICAL CHANGES IN HUMAN BRAIN
483
TABLE 12 Whole brain: Weights of constituents in grams
FETUS
3
MONTHS
FETUS
CHILD
CHILD
CHILD
ADULT
ADULT
ADULT
7 MONTHS
1 MONTH
3 MONTHS
8 MONTHS
21 YEARS
35 YEARS
67 YEARS
Whole brain
17.08
119.0
457.4
585.2
492.5
1122.4
1158.3
1297.9
Water
15.70
107.7
401.7
507.5
421.0
867.2
848.0
1020.0
Solids
1.38
11.25
55.74
77.58
71.54
255.2
310.3
278.0
Phospha
tids ....
0.178
1.476
9.158
11.250
15.228
65.05
73.67
81.93
Cerebro
sides . . .
0.000
0.000
0.169
1.590
2.266
13.479
27.207
21.081
Sulpha
tids ....
0.027
0.321
1.017
3.138
2.744
19.718
19.621
17.296
Choles
terol . . .
0.099
1.154
7.453
9.906
5.666
40.058
50.604
34.120
Total lipins.
0.304
2.951
17.774
25.896
25.863
138.23
171.02
154.27
Total pro
teins
0.644
4.736
21.439
31.973
30.730
91.305
103.65
98.00
Organic
extrac
tives . . .
0.263
2.106
11.116
13.435
9.811
13.892
24.363
12.639
Inorganic
extrac
tives . . .
0.171
1.440
5.362
6.228
5.180
11.633
11.431
13.018
Total ex
tractives..
0.434
3.546
16.478
19.663
14.991
25.525
35.794
25.657
Lipin
sulphur.
0.0005
0.0060
0.0207
0.0627
0.0620
0.3870
0.3880
0.3453
Protein
sulphur.
0.0044
0.0333
0.1300
0.2230
0.3310
0.6051
0.4973
0.7938
Neutral
sulphur.
0.0026
0.0214
0.1007
0.1456
0.0814
0.1398
0.2623
0.1767
Inorganic
sulphur.
0.0002
0.0024
0.0192
0.0270
0.0514
0.0236
0.1011
0.0365
Total sul
phur.. .. . .
0.0077
0.0631
0.2706
0.4583
0.5248
1 . 1555
1.2487
1.3525
484
C. G. MACAETHUR AND E. A. DOISY
TABLE \2— Continued
FETUS
3
MONTHS
FETUS
7
MONTHS
CHILD 1
MONTH
CHILD 3
MONTHS
CHILD
8
MONTHS
ADULT
21
TEARS
ADULT
35 TEARS
ADULT
67 TEARS
Lipin phosphorus .
0.0075
0.0643
0.3747
0.5020
0.6206
2.0980
3.2550
3.2360
Protein
phosphorus .
0.0043
0.0102
0.0319
0.0533
0.0591
0.1775
0.1871
0.1782
Organic phosphorus .
0.0044
0.0333
0.1639
0.2969
0.1600
0.1489
0.6054
0.1262
Inorganic phosphorus .
0.0096
0.0738
0.3758
0.5415
0.2926
0.7241
0.6356
0.7691
Total phosphorus . . .
0.0258
0.1821
0.9463
1.2836
1.1323
3.9585
4.6831
4.3095
Figure 1 was plotted from the data in this table relating to the earlier period of growth.
CHEMICAL CHANGES IN HUMAN BRAIN
485
TABLE 13 Whole brain: Milligrams added per day
UP TO 3-MONTH
FETUS
3-MONTH
TO
7-MONTH
FETUS
7-MONTH
FETUS TO
1-MONTH
CHILD
1-MONTH
TO
3-MONTH
CHILD
3-MONTH
TO
8-MONTH
CHILD
8-MONTH
TO 21-YEAR
Whole brain
Water
190.0
174.0 15.3
1.98 0.0 0.30 1.10
848.0
766.0
82.3
10.80 0.0 2.45
8.79
3764.0
3270.0 494.0
85.3 1.88 7.73 70.0
2127.0
1763.0 364.0
34.9 23.7 35.4 40.9
501.6
417.0 84.6
26.3 4.07 2.99 0.74
131.2 113
Solids
18 2
Phosphatids
5.4
Cerebrosides
1.4
Sulphatids
2 2
Cholesterol
4 4
Total lipins
3.38
22.04
164.9
135.1
33.9
13 4
Total proteins
7.16
2.81 1.90
34.1
15.4 10.6
185.6
100.1 43.6
175.6
38.7 14.4
38.5
7.2 5.2
5 1
Organic extractives
Inorganic extractives ....
-0.6 -0.3
Total extractives
4.81
26.0
143.7
53.1
11.4
-0.3
Lipin sulphur
0.006 0.049 0.029 0.002
0.05 0.24 0.16 0.02
0.16 1.07 0.88 0.19
0.70 1.55 0.75 0.13
0.08 0.61 0.01 0.11
0.04
Neutral sulphur
Inorganic sulphur
0.0 -0.01
Total sulphur
0.086
0.47
2.30
3.13
0.81
0.03
Lipin phosphorus
Protein phosphorus
Organic phosphorus
Inorganic phosphorus. . . .
0.083 0.048 0.049 0.107
0.47 0.081 0.24 0.54
3.45 0.24 1.45 3.36
2.12 0.36 2.22 0.93
1.01 0.09 0.0 0.17
0.27
0.01
-0.02
0.03
Total phosphorus
0.287
1.30
8.50
5.62
1.27
0.29
A part of these data are plotted in graph 2.
TABLE 14 Whole brain: Average percentage increase per day
Whole brain
Water
Solids
Phosphatids
Cerebrosides
Sulphatids
Cholesterol
Total lipins
Proteins
Organic extractives. . Inorganic extractives Total extractives
3-MONTH
FETUS
7-MONTH
FETUS
1-MONTH
3-MONTH
2.3
1.7
0.88
0.26
2.1
1.7
0.88
0.23
2.4
1.7
1.0
0.36
2.3
1.8
0.79
0.36
0.0
0.0
4.7
1.6
2.7
1.9
1.3
1.1
2.5
1.8
1.1
0.1
2.2 •
1.8
1.3
0.32
2.3
1.6
1.1
0.5
2.3
1.7
0.42
0.13
2.2
1.6
0.56
0.26
2.3
1.7
0.6
0.15
8-MONTH
0.028
0.04
0.046
0.03
0.057
0.072
0.02
0.03
0.02
0.00
0.00
0.00
These data were estimated from curves similar to, but larger than curves (1). These were plotted from data in table 10.
In the calculation from the curves a period of one-half month before and onehalf month after each age was used. It is believed that the enormous figures for rate of growth sometimes presented for early fetal life are due to the method of calculating from the weight at the beginning of the period. When the growth rate is changing rapidly, the error in such calculations is very large.
The curves in graph 3, excepting extractives (c), are plotted from this table,
TABLE 15 Whole brain: Average percentage increase per day
8 MONTH21 YEARS
Whole brain
Water
Solids
Phosphatids
Cerebrosides
Sulphatids
Cholesterol
Total lipins
Proteins
Organic extractives. . . Inorganic extractives. Total extractives
3-7
MONTH FETUS
7 MONTH
FETUS 1 MONTH
1 MONTH3 MONTH
3 MONTH8 MONTH
1.25
1.31
0.41
0.067
1.24
1.28
0.39
0.065
1.30
1.47
0.55
0.081
1.31
1.59
0.34
0.13
0.00
(2.23)
2.69
0.14
1.41
1.16
1.70
0.075
1.46
1.63
o;47
0.073
1.36
1.59
0.62
0.093
1.27
1.42
0.66
0.087
1.28
1.52
0.32
0.046
1.32
1.28
0.25
0.067
1.30
1.44
0.29
0.048
0.013
0.014
0.01
0.012
0.016
0.018
0.018
0.014
0.007
0.0
0.0
0.0
Calculated from data in table 11. The average number of milligrams added per day was divided by the average weight for the given period, instead of the weight at the beginning of the period, as is usually done. When there are rapid changes in weight, this method is not as accurate as that used in table 12. It is believed that the temporary rise in growth at about the seventh month of fetal life is due to the method of calculation.
The curve marked extractives (c) in graph 3 was plotted from the above data.
486
SUBJECT AND AUTHOR INDEX
ACTIVITY of the nervous system. III. On the amount of non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic 397
Albino mouse. The nervus facialis of the. .. . 81
rat in Miiller's fluid. Factors influencing the behavior of the brain of the. ..411
rats during twenty-four hovirs after
feeding. Metabolic activity of the nervous system. III. On the amount of non-protein nitrogen in the brain of 397
Allen, William F. Application of the March! method to the study of the radix mesencephalica trigemini in the guineapig 169
Allis, Edw.\rd Phelps, Jr. The ophthalmic nerves of the gnathostome fishes 69
Arey, Leslie B. A retinal mechanism of efficient vision 343
Ayers, Howard. Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the ' nose' 323
BEHAVIOR of the brain of the albino rat in Miiller's fluid. Factors influencing
the 411
Brain during growth. Quantitative chemical
changes in the human 445
of albino rats during twenty-four hours
after feeding. Metabolic activity of the" nervous system. HI. On the amount of
non-protein nitrogen in the 397
of the albino rat in Miiller's fluid. Factors influencing the behavior of the 411
CELLS in normal, subnormal, and senescent human cerebella, with some notes on functional localization. A preliminary quantitative study of the Purkinje. 229
tunnel space, and Nuel's spaces in the
organ of Corti. The development of the pillar 283
Cell with especial consideration of the ' Golginet' of Bethe, nervous terminal feet and the 'nervous pericellular terminal net' of Held. On the finer structure of the synapse of the Mauthner 127
Cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the 'nose.' Vertebrate 323
Cerebella, with some notes on functional localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human 229
Changes in the human brain during growth. Quantitative chemical 445
Chemical changes in the human brain during growth. Quantitative 445
Corti. The development of the pillar cells, tunnel space, and Nuel's spaces in the organ of 283
DEVELOPMENT of the pillar cells, tunnel space, and Nuel's spaces in the
organ of Corti. The 283
DoiSY, E. A., Mac.;\rthur,C. G.,and. Quantitative chemical changes in the human brain during growth 445
487
EFFICIENT vision. A retinal mechanism of 343
Ellis, .Roiiert S. A preliminary quantitative .study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional localization 229
FACIALIS of the albino mouse. The nervus 81
Factors influencing the behavior of the brain of the albino rat in Miiller's fluid 411
Fiber in teleosts. Concerning Reissner's 217
Fishes. The ophthalmic nerves of the gnathostome 69
Fluid. Factors influencing the behavior of the brain of the albino rat in Miiller's. ... 411
Formation of the 'nose.' Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the. . 323
Functional localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on 229
GNATHOSTOME fishes. The ophthalmic nerves of the 69
Golgi. Frontispiece. Portrait of Professor Camillo 168
'Golgi-net' of Bethe, nervous terminal feet and the ' nervous pericellular terminal net' of Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 127
Growth. Quantitative chemical changes in the human brain during 445
Guinea-pig. Application of the Marchi method to the study of the radix mesencephalica trigemini in the 169
HEAD, resulting in the formation of the 'nose.' Vertebrate cephalogenesis. IV. Transformation of the anterior end of
the 323
Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the ' Golgi-net' of Bethe, nervous terminal feet and the 'nervous
pericellular terminal net' of 127
Human cerebella, with some notes on functional localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent 229
JORDAN, HovEY. Concerning Reissner's fiber in teleosts 217
KOMINE, Shigeyuki. Metabolic activity of the nervous system. III. On the amount of non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding 397
LARSELL, Olof. Studies on the nervus terminalis: Mammals 1
• Studies on the nervus terminalis:
turtle 423
488
INDEX
Localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional 229
MACARTHUR, C. G., and DoieY, E. A. Quantitative chemical changes in the human brain during growth 445
Mammals. Studies on the nervus terminalis. 1
Marchi method to the study of the radix mescncephalica trigemini in the guinea-pig. Application of the 169
MjVRCI, Kitoy.\su. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 'Golgi-net' of Bethe, nervous terminal feet and the ■ nervous pericellular terminal net' of Held. 127
. The effect of over-activity on the morphological structure of the synapse. 253
Mauthner cell with especial consideration of the * Golgi-net' of Bethe, nervous terminal feet and the ' nervous pericellular terminal net' of Held. On the further structure of the synapse of the 127
Mesencephalica trigemini in the guinea-pig. Application of the Marchi method to the study of the radix 169
Metabolic activity of the nervous systern. III. On the amount of non-protein nitrogen in the brain of albino rats during twentj'-four hours after feeding 397
Morphological structure of the synapse. The effect of over-activity on the 253
Mouse. The nervus facialis of the albino 81
Miiller's fluid. Factors influencing the behavior of the brain of the albino rat in. . . 411
NERVES of the gnathostome fishes. The ophthalmic 69
Nervous system. III. On the amount of nonprotein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the 397
— terminal feet and the 'nervous pericellular terminal net' of Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 'Golgi-net' of Bethe 127
Nervus facialis of the albino mouse. The.... 81
terminalis: Mammals. Studies on the 1
turtle. Studies on the 423
Net' of Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 'Golgi-net' of Bethe, nervous terminal feet and the ' nervous pericellular terminal 127
Nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the nervous system. III. On the amount of non-protein 397
Non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the nervous system. III. On the amount of 397
' Nose.' Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the . . 323
Nuel's spaces in the organ of Corti. The development of the pillar cells, tunnel space, and 283
OGATA, D., and Vincent, Swale. A contribution to the study of vasomotor
reflexes 355
Ophthalmic nerves of the gnathostome fishes .
The 69
Organ of Corti. The development of the pillar cells, tunnel space, and Nuel's
spaces in the. 283
Over-activity on the morphological structure of the synapse. The effect of 253
PILLAR cells, tunnel space, and Nuel's spaces in the organ of Corti. The development of the 283
Pl.^nt, J.\mes Stu.\rt. Factors influencing the behavior of the brain of the albino
rat in Miiller's fluid 411
Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional localization. A preliminary quantitative study of the 229
RADIX mesencephalica trigemini in the guinea-pig. Application of the Marchi
method to the study of the 169
Rat in Miiller's fluid. Factors influencing the
behavior of the brain of the albino 411
Rats during twenty-four hours after feeding. » Metabolic activity of the nervous systeni. S III. On the amount of non-protein ni trogen in the brain of albino 397
Reflexes. A contribution to the study of
vasomotor 355
Reissner's fiber in teleosts. Concerning 217
Retinal mechanism of efficient viaion. A 343
Rhinehart, D. a. The nervous facialis of the albino mouse 81
SPACE, and Neul's spaces in the organ of Corti. The development of the pillar cells, tunnel 283
Spaces in the organ of Corti. The development of the pillar cells, tunnel space, and Nuel's 283
Structure of the synapse of the Mauthner cell with especial consideration of the ' Golginet' of Bethe, nervous terminal feet and the ' nervous pericellular terminal net' of Held. On the finer 127
Structure of the synapse. The effect of overactivity on the morphological 253
Synapse of the Mauthner cell with especial
consideration of the ' Golgi-net' of Bethe,
• nervous terminal feet and the 'nervous
pericellular terminal net' of Held. On
the finer structure of the 127
The effect of over-activity on the morphological structure of the 253
System. III. On the amount of non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the nervous 397
TELEOSTS. Concerning Reissner's fiber in 217
Terminalis: Mammals. Studies on the nervus 1
turtle. Studies on the nervus 423
Terminal net' of Held. On the finer structure of the synapse of the Mauthner cell with especial corisideration of the 'Golginet' of Bethe, nervous terminal feet and the ' nervous pericelhJar 127
Transformation of the anterior end of the head, resulting in the formation of the 'nose.' Vertebrate cephalogenesis. IV.. 323
Trigemini in the guinea-pig. Application of the Marchi method to the study of the radix mesencephalica 169
Tunnelspace.and Nuel'sspacesin theorganof Corti. The development of the pillar cells 283
Turtle. Studies on the nervus terminalis. . . 423
VAN DER STRICHT, O. The development of the pillar cells, tunnel space, and Nuel's spaces in the organ of Corti. 283 Vasomotor reflexes. A contribution to the study of 3.55
Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the 'nose'; . . . 323 Vincent, Swale, Ogata, D., and. A contribution to the study of vasomotor reflexes. 355 Vision. A retinal mechanism of efficient 343
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