A REVIEW OF SOME RECENT LITERATURE ON THE OF THE CENTRAL NERVOUS

CHEMISTRY
SYSTEM.

By ISADOR H. CORIAT, M.D.,

Worcester Insane Hospital.

The last few years have witnessed a marvelous impetus and great evolution in our ideas of anatomical and chemical facts concerning the central nervous system. The cerebro-spinal fluid has also shared in this advance, partly as the result of independent study, but chiefly because of its intimate relation to the nerve structures. The literature on the subject is scattered through the various journals and reports, but outside of THUDICHUM'S book on the chemical constitution of the brain of man and lower animals, and of SICARD'S recent work on the cerebro-spinal fluid, there has been no serious attempt to summarize the recent publications on the chemistry of the nervous system, both in normal and pathological states. It seems opportune, therefore, to review the most available facts along these lines, and point out in what manner these may be utilized to stimulate further research. Of course, in the limits imposed by a review, only the most important papers can be abstracted. The work on neuro-chemistry has been pushed in several directions, of which the principal ones merit the following subdivisions:

1. More systematic attempts at classifying the various substances of the brain.

2. The isolation of nerve products by newer methods.

3. The further ultimate analysis of these products.

4. The chemistry of the finer structure of the nerve cells, including the micro-chemistry of various stains.

5. The autolysis of brain tissue.

6. Analysis of the brain and cord in various normal and pathological states.

7. The chemistry of the cerebro-spinal fluid, particularly as a medium for the various products of nerve degeneration.

8. The physiological action of various normal and pathological nerve products.

The substances so far isolated from the brain follow. The classification is merely a tentative one and must not be looked upon as

final. It is partly adopted from THUDICHUM and KоCH and partly the result of my own observations.

3. Neuroglobulin, coagulating at 45°-50° C. (According to HALLIBURTON it is the coagulation of this substance in the nerve cells, which is the physico-chemical cause of death from hyperpyrexia).

4. Neurostromin (in traces).

5. Nucleo-proteid (LEVENE, HALLIBURTON, SCHKARIN).

6. Neurokeratin (KÜHNE and CHITTENDEN).

7. Albumoses and Peptones.

C. Extractives.

1. The purin bases of the nucleo-proteids (Adenin, guanin, hypoxanthin).

2. Pyramidin bases (thymin and cytosin).

3. Amido-acids (leucin and tyrosin).

4. Urea (also a normal constituent of the cerebro-spinal fluid).

D. Carbohydrates.

1. Inosite.

2. An unknown carbohydrate which gives the furfurol reaction and is probably related to the pentoses.

3. Galactose (a split-product of cerebrin).

4. Dextrose (in the cerebro-spinal fluid)-CORIAT.

5. Pyrocatechin (in the cerebro-spinal fluid ?)—HALLBURTON.

6. Glycogen (?),

E. Acids.

I. Nucleic acid.

2. Sarcolactic acid.

3. Lactic acid (optically inactive ethylidene lactic acid. This is the result both of post-mortem decomposition and of long continued activity in the central nervous system, as in convulsive seizures. In both cases, the acid passes into the cerebro-spinal fluid).

4. Glycerophosphoric acid (a decomposition product of lecithin).

5. Formic acid.

6. Acetic acid.

7. Succinic acid.

8. Stearic, oleic acid, palmitic acids (decomposition products of lecithin).

9. Litho- and Butophosphoric acid (THUDICHUM).

F. In Pathological Conditions.

1. Cholin (a decomposition product of lecithin-MOTT and HALLIBURTON, DONATH, WILSON, CORIAT).

2. Neurin.

3. Uric acid.

4. Kreatin.

5. Trimethylamin (a post-mortem product).

6. Neuridin.

G. Inorganic bodies. Sodum, potassium, ammonium, calcium and iron, present either as dissociated ions, or in organic combination. The radicles CI, SO, PO1, and CO, are also present as disociated ions or with the cations above mentioned.

H. Lecithins (Monophosphatids containing one nitrogen molecule in the proportion N:P=1:1). The various lecithins from eggs, barley, malt, yeast and brain show variations in the amounts of phosphorus and in the methyl content.

1. Lecithins (Stearylolely, margeryloleyl, palmityloleyl).

2. Amido-lecithins (amido-myelin). Contains two nitrogen molecules N;P=2:1.

3. Kephalins (P:N=1:1).

Kephalin
Oxykephalin

Peroxykephalin

Myelin

Paramyelin

Sphingomyelin

Assurin (N:P:=2:2).

4. Amido- Kephalins (amido-kephalin P:N=1:2).

I. Cerebrins.

1. Phrenosin

2. Kerasin (THUDICHUM)

3. Amidocerebrinic acid-glycosid (BETHE)

4. Phrenin

5. Cerebrin acid

Cerebrin acids

Sphaerocerebrin

Cerebrin phosphoric acid (BETHE)

J. Cholesterin (occurs both free and in the form of an ester).

K. Sulphur compounds (Cerebusulphatides and sulphatids of THUDICHUM). L. Amido-fats (Krinosin and Bregenin).

As a contrast, THUDICHUM's classification alone should be consulted (Die chemische Konstitution des Gehirns des Menschen und der Tiere, pp. 89-91), and the reader will also find there a minute discussion of these various products, with particular relation to their chemical reactions.

It is unnecessary to enter here into the details of the newer methods for the isolation of the various brain substances. The original papers must be consulted, of which reference is given in the bibliography affixed to this review. It suffices to mention THUDICHUM'S complete isolation methods, the acetone method of KOCH for the separation of lecithin, kephalin and cerebrin, LEVENE'S methods for the isolation of nucleic acid and the nucleo proteids, KOCH's modification

of the method of HERZIG and MEYER for the quantitative determination of lecithin by an estimation of the methyl groups, HALLIBURTON'S method for the detection of cholin in the cerebro-spinal fluid and blood, and CORIAT's method for the detection and quantitative estimation of cholin in nerve tissue.

The first serious attempt at the quantitative analysis of the brain in normal and diseased individuals, was that of GUTINKOV, who estimated water, fixed substances, nitrogen, sulphur and phosphorus, both in the white and grey matter. His series comprised 15 human foetal brains at about the third month, the brains of seven people who died suddenly without any previous illness, and of various mental and somatic diseases. These latter included three cases each of carcinoma and syphilis, two each of pulmonary tuberculosis, neurasthenia and senile dementia, four cases of acute alcohol poisoning, seven of chronic alcoholism, and one case each of post-epileptic dementia, idiocy, postmaniacal dementia, general paralysis, epilepsy, syphilitic pseudo-paralysis, mania and stuporous melancholia. A summary of his various findings as compared with the averages for normal brains, is readily seen from the following table. For the normal human brain, as the average of seven analyses, the following figures are obtained, and it is with these that the pathological material is compared.

=normal. += increased.

Disease.

•+11+ 1++++ | Z++++ | Water in

gray sub.

Phosphorus

in white sub.

Nitrogen in

gray sub.

Nitrogen in

++++ +1+1++++++2 white sub.

The figures themselves, for which the original article must be consulted, are certainly far from convincing, the pathological material especially showing some glaring contraditions; for instance, the difference in the two analyses of neurasthenia and senile dementia. Furthermore, the figures on the percentage of water in general paralysis, are not as high as the marked pial oedema of this disease would lead us to believe.

THUDICHUM'S figures are the result of the working over of a large amount of material and of complex elaborated methods. For the gray matter of the human brain he gives the following results:

Substance.

Water

Neuroplastin

Ether extract (with kephalin, lecithin and cholesterin)
Cerebrosides, cerebrinic acid and myelin

Lecithin, kephalin and myelin (out of the last oily material) 0.780

Ether extract (kephalin, lecithin and cholesterin) 11.497

The fig

The following figures were established for the entire human brain, as the sum of results from separate analyses of the two hemispheres, cerebellum, mid-brain and medulla, gray and white matter. ures are given in grammes, and relate to the entire weight of the brain without membranes (1296 grammes).