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it is present in larger amount in the grey than in the white matter ;
in early than adult life ; in the brain than in the spinal coi<l ; in the
spinal cord than in ner\es. These facts are illustrated by the following
tables : —

1 iliiller, Amudeii der Chem. u. Pliarm. ciii. 141. See also Strecker, ihid. cv. 31G.
- Sec Kiihne, ' Crooniau Lecture,' Proc. Boy. Sot: vol. xliv (1888), p. 427.
•"• In the frog reflex time varieb from O'OOS to 0'01.5 sec. Reaction time in man varies
from 0-1-25 to -02 sec.



llll': NI'MJVors SYSTE.^I



517



rLToeutages of water '



I'onioii of iirivous
s\ sinir



Grey substance .
White substance
Spinal cord . .
^Nerves . . . .



1 11 fn'tiis A f.'c 20-30 Age 70-ni
(W) (\V) I (W)



1 1 87-92



(B)

S5



8.S X4

69 [ 72 70

— _ 7;j_7r, i —

— — 64-72







(H)


(V)


(M)


81

68


)-


86
70





68








57






A monatomic alcohol, especially abundant in white



Soli'/n. — The solid matters in the brain fall into several classes.

a. Proteids. These comprise about half the sf)lid.s in grey matter,
-•ibout one-foui'th of those in white matter, and about one-third of
those in nerve.

b. Albuminoids. Neurokeratin and nuclein.

c. Phosphorised constituents. Of these the most important are
protagon and lecithin, especially in grey matter.

d. Cerebrins. Certain nitrogenous substances of unknown com-
position.

e. Cholesterin
matter.

f. Extractives. Substances that occur in small quantities, such as
are fovmd also classified as extractives in muscular tissue (creatine,''
xanthine,-* hypoxanthine,^ inosite, lactic acid, leucine,^ uric acid, and
urea).

'f/. Gelatin and fat, derived from the adherent connecting tissue.

Ji. Inorganic salts. The total mineral matter varies according to
•ilifferent writers from O'l to 1 per cent. But little is known of the
function of the mineral constituents, and they may be here con-
veniently dismissed altogether with the following abbi'eviated table
from Geoghegan's ^ paper : —



In p.irts per 1000 of bi


aiii






1


1
Total iisli K 1 Xa Jig


Ca


CI


PO^


CO3


SO, |Pe(P0j3!


2-9 to 7-] 0-6 to 1-7 0-4 to M 0-0 to 007


0-005
to 0-02


0-4
to 1-3


0-9
to 2-0


0-2
to 0-7


0-1 0-01

to0-2;to0-09

1



1 The above table is constructed from the published observations of Weisbach (W)
(see Ganigee, Physiol. Chem. p. 445), Bernardt (B) {Ibid. 446), Petrowsky (P) {Pflilger's
Archiv, vii. 367), Moleschott (M) {see Charles, Physiol. Chem. p. 33.5), and De Regibus (R)
{Mah/s Jahresb. xiv. 346).

- According to Miiller, creatine is present in human brain, but absent from that of the
ox. It was found by Stiideler in pigeon's brain {Journ. jjrakt. Chem. Ixxii. 256).

^ Stiideler, Ann. Chem. 11. Pharm. cxvi. 102; Scherer, Ibid, c^-ii. 314.

■* Miiller, J/;?V7, ciii. 131. '■> Zeif. physiol. Chem. i. 3'SO.



518 THE TISSn:s AND OKGAXS OF THE EDDY

The grey matter is stated by Schlossberger to be richer in total ash,
but poorer in phosphates, than the white matter ; Petrowsky, on the
other hand, obtained more phosphoric acid from grey than from white
matter.

Tlie following table gives some of the typical quantitative analyses
that have been made of the propoi'tion in which the principal solid
constituents occur in dijfferent nervous structures : —



Portion of nervous
svstem



Leci- Cliolesterin! r^ .k_:„ Xetirokera-



Other



thin anrl fat



tin *'''^'"''

matters



I
Grey matter of ox '

bram(PetrowskT) 55'37
"^liite matter of ox

brain (ihid.) . . 2472

Spinal cord (Mole- "'

schott) .... 23-8 75-1 1-1



17-24 18-68 0-53 GTl I'^o

9-90 .)1-91 9-.55 3-34 0-57



Human sciatic ners-e | "

(Josephine Cheva- i I

lier') 36-8 32-57 12-22 11-.30 3-07 4-0 —

After having looked at the nervous tissues as a whole, and before
going on to describe in detail the principal organic substances con-
tained in them, it will be next convenient to take the individual
histological elements and the facts we know respecting their chemical
composition. Here we have, to a large extent, to rely upon the methods
of micro-chemistry, which almost necessarily afford us limited infor-
mation.

Nerve-cells. — These cells vary much in size and shape in different
parts of the central nervous system ; the body of the cell is proto-
plasmic, and therefore chiefly proteid in nature. In this way the high
percentage of proteids in grey mater Ls accounted for.

In many nerve-cells masses of a greyish pigment are often present ;
this pigment does not seem to have been specially investigated, but is
no doubt ultiuiately derived from hfemoglobin like the other pigments
of the body. The nerve-cells of the ganglia of the worm Aphrodite
aculeata are tinged red. This is due to the presence of haemoglobin. -
From this fact, and from the fact also of the greater vascularity of
grey as compared with white matter, we may assume, as Gamgee says,
that respiratory exchanges go on more actively in nerve-cells than in
nerve-fibres.

Nerve-cells have always a well-marked nucUvs. The substance of
1 ZeU.physioh Chem. x. 97. * Gamgee, Physiol. Chem. p. 420.



THE NERVOUS SYSTEM 519

which it is composed, uppears to I)e one of the class of phosphorised
.•ill)uiniiioi(l.s known as nucleins ; v. Jaksch ' separated it from the
brain, and Geoghegan ^ estimated that the amount present in that
organ was 0"14 per cent. Elementary analysis shows very marke<l
discrepancies from the analyses that have been made of nuclein
obtained from other sources, and confirms the decision which we have
before arrived at (p. 203), of the possiliility either of several varieties of
nuclein existing, or that nuclein is not a chemical unit, but a mixture
of phosphorised substances.

Nerve-Jibres vary in size from 72^^-571 to xxg^o- "ich in diameter. Each
nerve-fibre consists of three parts : a central portion known as the axis-
cylinder, a transparent outer sheath with nuclei, called the primitive
sheath, and between the two a white highly refracting substance
known as the medullary sheath, or white substance of Schwann, which
is interrupted at intervals called the nodes of Ranvier. The axis-
cylinder takes origin as a process of a nerve-cell. During its passage
through the grey matter it is naked ; when it reaches the white matter-
of the nerve-centres it acquires a medullary sheath ; and it is not
until it lea^■es the brain or spinal cord and becomes bound with other
nerve-fibres to form a nerve that it receives the outer or primitive
.sheath. The optic and auditory nerve-fibres, however, are never
covered by this outer sheath.

Many nene-fibres retain both sheaths until they reach their-
terminations. Others, especially the small nerve-fibres, pass through,
ganglia (sympathetic chain, semilunar ganglia, (kc), and when they
emerge from these have lost their medullary .sheath (GaskelP) : they
are then known as non-medullated nerve-fibres. These are e.specially
concerned in supplying the muscular fibres of viscera and blood vessels.

Nerve-fibres may be classified according to the direction in which
they normally transmit impulses into efferent (from nerve-centres to
periphery), atferent (from periphery to nerve-centres), and intei'central
(from one part of the nerve-centres to another).

Gaskell has more recently classified the efierent nerve-fibi'es inta
two sets, according to the effect of the impulses they transmit upon the
metabolic processes of the organs they supply. The metabolism or
tissue change of a living structure consists of two parts : a building-up
process, assimilation or anabolism, and a breaking-down proce.ss of the
nature of combustion, or katabolism. The nerves the excitation of
which produces activity of the organ they supply are those which

' V. Jaksch, Pflilger's ArcJiiv, xiii. 469.
2 Geoghegau, Zeit. physiol. Cliem. i. 330.
^ Gaskell, Journ. of Physiol, vii. 1 et scq.



520 THE TISSUES AND OJiGANS OF THE I'.DDY

produce katabolism, and ai-e called katabolic nerves : such nerves are
the motor and secretory nerves. The nerves the excitation of which
produce a lessening of the activity of the organs they supply are those
which allow of building up, or anabolic changes to occur in those
organs. They are therefore called anabolic nerves. Such nerves are
the inhibitory nerves of the heart, blood-vessels, and viscera.

The primitive slteath, or neurilemma, in the case of motor nerves
becomes continuous with the sarcolemma of the muscular fibres they
supply ; and the chemical characters of both neurilemma and sarco-
lemma appear to be iflentical, both consisting of a homogeneous
substance of the nature of elastin. It is, however, more soluble in
alkalis than the elastin of elastic fibres [see p. 40")).

The medullary sheath, or white substance of Schwann. This is
generally said to consist of myelin. This substance is not, however, a
•chemical unit, but a mixture of various substances of which complex
l^hosphorised fats like lecithin, with cholesterin and cerebrin, are
the chief. During life it is semi-liquid ; after death it solidifies ;
in certain j)athological conditions it becomes very liquid (Wallerian
degeneration). Like the fat of adipose tissue, it reduces solutions of
•osmic acid, and the deposit of metallic osmium so produced makes it
black. This fact is of great value to the histologist.

Kiihne and Ewald ' found that the axis cylinder and white substance
■of Schwann are covered with a delicate sheath of a horny substance,
and that the two sheaths are connected by numerous transverse and
oblique fibrils. The rod-like structures described by MacCarthy ^ in
the medullary substance are in all probability part of this horny net-
work. The myelin lies in the intei-stices of the mesh-work.

This horny matter is called neiirokeratiti ; like the keratin of
■epidermic structures it resists the action of reagents very powerfully.
It is found, not only in medullated nerve-fibres, but in grey matter, and
we have already come across it in the retina (pp. 457, -1:59). The chief
interest of this material is derived from embryological considerations.
Both epidermis and nervous tissues are derived from the same layer of
the blastoderm, namely, the epiblast or ectoderm ; both contain at least
■one chemical substance in common, viz. keratin.

In the Crustacea, chitin takes tlie place of keratin in the epidermal
structures, and similarly neurochitin takes the i)lace of neurokeratin
in forming a skeletal support to the nerve-fibres.

The following is the method that is adopted for tlie preparation
of neurokeratin : Ox's brain is finely divided, washed with water,

1 Verhandl. il. natnrhist. mcd. Vcreins xii Heidelberg, vol. i. Heft 5.
- MacCarthy, Quart. J. Mir. Seieiice, 1S70.



'11 IK NKUVDIS SVSTKM 521

<ligeste«l ill cold ulcohol, fully extruftctl witli ctluT, dricil and powdered.
The powder is boiled with alcohol to extract cerebrin ; the residue is
boiled with water, digested with artificial gastric juice, and then with
-artificial pancreatic juice. The undigested residue consists chiefly of
neurokeratin, and is purified by thorough washing in succession with
dilute alkali, acetic acid, alcohol, and ether, and dried.

Neurokeratin has the same general properties as keratin. It is,
however, less easily soluble than keratin in boiling caustic potash and
in boiling dilute sulphuric acid. AVhen burnt it emits the chai'acter-
istic odour of burning horn. When treated with sulphuric acid it
yields leucine and tyrosine. Kiihne and Chittenden,^ who have recently
investigated the subject, give the following percentage composition for
neurokeratin: C, 56-99; H, 7-5-1 ; N, 13-15 ; S, 1-87; O, 20-45.
(Compare analyses of keratin, p. 453.) They also made some estima-
tions of the amount of neurokeratin in difi;erent jiarts of the nervous
system ; they found the percentage in nerve 0-3 to 0-6 ; in grey matter,
0-3; but in white matter it is much higher, 2-2 to 2-9.

Cerebrin is much more abundant in white matter, and in nerve than
in grey matter (see table, p. 518) ; this favours the view that it is one
of the constituents of myelin or the white sheath of ScliAvann.

T/ie axis-cylinder is the long process of a nerve-cell. It is solid
<luring life, and is composed of a mixture of proteids with complex fats.
It dissolves in 0-1 per cent, hydrochloric acid and in 10 per cent,
sodium chloride solution. It is made up of a number of filjrilla^ ; this
gives the axis-cylinder a longitudinally striated appearance. The axis-
cylinder itself and the fibrilhe that result from its subdivision are not
stained by osmic acid, but are stained purplish by gold chloride, from
the deposit of metallic gold in them. They are stained reddish violet
by a solution of copper sulphate in ammonia. The fibrilla? as seen in
the terminations of sensoi-y nerves, e.g. in the cornea, often show
varico.sities, or little swellings, along their course.

The axis-cylinder is the essential part of a nerve-fibre, being the
only part which is continuous from one end to the other. Along it
nervous impulses are transmitted ; the only known chemical change -
that occurs on activity is the increase of acidity already alluded to
(p. 515). The refractive index of the living axis-cylinder is 1-367 ;
this does not alter during activity (Gross ■^).

' Zcit. BioL xxvi. 291.

^ Helniholtz (Comptes rend. Isxxvii. 533), Heideiiluiiii [Stiidieinihijiiiol. Iiist.Brcslau,
IV. 250), and Eolleston (J. P/ii/siol. xi. 208) were not able to find any rise of temperature
accompanying this change. On the death of nerve, however, heat is given off (Rolleston).

5 Gross, Pfli'igcr's Archiv, xlvi. 56.



522 THE TISSn:S AND ORGANS OY THE Br»DY

Development of nerre-fihrei. — Tliese are now generally regarded as being epi-
blastic. The discovery of neurokeratin in them is very distinctly in favour of
this view from a chemical standpoint, Tlie axis-cylinder is undoubtedly an
enormously long process of a nerve-cell, and grows outwards to the periphery.
The formation of the sheaths is, however, still a jwint upon which difference of
opinion prevails. We have seen that the medullary sheath is divided at regular
intervals into a series of intemodes. each of which possesses a nucleus, and may
therefore be looked upon as representing a number of cells wrapped round the
axis-cylinder, the primitive sheath being homologous to the cell-membrane. The
fatty matter of the medullary sheath may accumulate within the cell as fat does-
in connective-tissue cells in the development of adipose tissue.'

This view of the formation of the sheaths by the linear coalescence of
elongated cells appears to gain support from the beha\*iour of silver nitrate,
which produces the appearance of a black line across the fibre at each node,,
apparently dne to the existence of intercellular or cementing material there. At
the same time the part of the axis-cylinder that is exposed at the nodes is lightly
stained, so that the appearance of a cross at each node is produced. The part of
the axis-cylinder which is stained in this way sometimes exhibits transverse
striations known as Fromann's lines.

Degeneration of nerre-fihres. — Xasse first noticed in 1839 the breaking up of
the white substance of Schwann in the peripheral end of a cut nerve. In ISS?
Waller showetl that the process depended on the isolation of a nerve-fibre from
its nutritive or trophic centre. Since then our knowledge of Wallerian degenera-
tion has been advanced by many researches, notably those of Eanvier.- The
chief features in this degeneration are a multiplication of the nuclei and a great
liquefaction of the myelin. This change occurs simultaneously in the whole
length of the nerve-fibre, which is severed from its trophic centre. The myelin
collects into irregular drops, which bulge the primitive sheath in parts, and
break up the continuity of the axis-cylinder. Ultimately the liquefied myelin
penetrates into the connective tissue of the nerve, and is absorbed and removed
by the lymphatics.

In the nerve-centres certain tracts of fibres can be readUy traced when the
grey matter from which they originate is removed or injured, or when they are
disconnected from this grey matter, as by a hfemorrhage or other means. The
pyramidal tracts are well-known examples of nervous paths, of which we have
derived much anatomical information by the Wallerian method. The individual
fibres undergo the same changes as those just described in the case of nerve : but
in the nerve-centres there is in addition a great overgrowth of connective-tissue-
neuroglia : this stains very readily with certain histological staining reagents,
such as carmine and aniline blue-black, and so the degenerated tracts can be
easily traced in sections, even with the naked eye.

The most marked feature of this degeneration is the change in the white sub-
stance of Schwaim ; though sptoken of as a fatty degeneration we must remember
that myelin is very largely of a fatty nature to begin ^viih, and we have still to
wait for a more exact definition of the change in question.

Hoppe-Seyler,' in a case of atrophy of the optic nerve, on comparing the



1 Quain's Anat. ii. 178, 179.

- Ranvier, Lecons, 1878; Covn)t. rend. Ixxviii.

5 Physiol. Chem. p. 689.



THE Ntnjvous svsTi:.A[ 528

diseased with tiic licaltliy nerve, found that in the fornrier tlie substances soluble
in ether were diminished, and the amount of gelatin increased, owing to connec-
tive-tissue overgrowth.

Havintj thus described the histological elements of the nervous
tissues, we must now return to tlie various chemical materials of
which they are composed. Incidentally, as we have gone along, it has
been convenient to describe a few of them ; we need therefore not
return again to nuclein, neurokeratin, the extractives, or the salts.
Referring to the list already given of the chief constituents of nervous
tissue (p. 517), it will be seen that we have still to descrilie the pro-
teids, the phosphorised constituents, the cerebrins, and cholesterin.



THE PROTEIDS OF NERVOUS TISSUE

Notwithstanding the quantitative importance of the proteids in
nervous tissue, especially in gi'ey matter, comparatively little work has
been done on the sulyect. Most writers are content to allude to them
as proteid matter, or to use the term albumin synonymously with
proteid. In a recent research by Baumstark,' he speaks of the proteids
as resembling casein. Petrowsky,^ who made a few definite experi-
ments on the subject, describes : —

1. A globulin : somewhat I'esembling myosin.

2. An albumin : coagulated at a temperature of 75" C. ; this is
especially abundant in the grey matter.

In my own researches on the sulyect, in which the moi'e recent
methods of the separation of proteids by means of fractional heat-
coagulation and saturation with various neutral salts were employed,
the following are the chief results : —

The proteids present are : —

1. A proteid which, like cell-globulin n, coagulates at 45°-47°C.

'2. A proteid which, like myosinogen, coagulates at 56° C. This is
absent in white matter.

3. A proteid with the properties of cell-globulin, coagulating at
75° C.

These are all globulins : albumins are absent in fresh brain ; so al.so
are albumoses and peptones.

There is no doubt that the greater part of the proteid matter in
nervous tissue is derived from nerve-cells and the axis-cylinders of
nerve-fibres.

' Baumstark, Zeit. phijsiol. Chem. ix. 14.")-150.
- Petrowsky, Pfliiger's ArcJiiv, vii. 370.



r>24 THE TISSUES AND ORGANS OF THE BODY



THE PHOSPHOKISED CONSTITUENTS OF NERVOUS TISSUE

111 tlie year 1865 Liebreich' sepHifitecl from the brain a material he
"termed jrrotagon ; he further found tliat ^^■hen decomposed by baryta-
water it yielded two acids — stearic acid and glycero-phosphoric acid —
and a base called choline.

Hoppe-Seyler, and Diaconow ^ workin<^ under Huppe-Seyler's direc-
tion, denied the existence of this substance protagon, and considered
that it was a mere mechanical mixture of a phosphorised fat called
lecithin, with a nitrogenous non-phosphorised substance called cerebrin.
Lecithin yields the same three decomposition j^roducts that were ob-
tained from protagon by Liebreich. Diaconf)w's elementary analyses
were, however, far from convincing.

The subject in this country was taken up by Gamgee and Blanken-
horn -^ ; and the result of their work has been that Liebreich's discovery
has been fully verified. They showed that protagon is a perfectly
definite crystalline substance of constant elementary composition.
They also showed that even prolonged treatment with alcohol and ether
■will not extract lecithin from protagon, as alleged by Diaconow.
When protagon is digested with alkalis it yields the same decom-
position products as lecithin does. Bavinistark ' lias since this fully
confirmed Gamgee's work.

An elaborate research by Thudichum'' has led him to the conclusion
that there are three groups of phosphorised substances in the brain,
which he terms keiDhalines (very soluble in ether), myelines (far less
soluble in ether), and the lecithines (characterised by their extreme
instability). In each of these groups there are several members, the
•empirical formuhe of which ha^•e been calculated. Though somewhat
indefinite, Thudiehum's researches demand a passing notice in this
short historical sketch of the chief steps by which our knowledge on
this subject has been attained.

We can now pass on to a more detailed consideration of lecithin,
protagon, and their products of decoiiipositit)n.

' Liebreich, AniidJcii dcr CJiciii. ii. FJiariii. cxxxiv. '2it.

- Diaconow, Coitralhl. f. <1. mod. Wissensch. 18C8, p. il7.

■" Gamgee and Blankenhorn, Jourii. of Physiol, ii. 11:5. Fioin this paper and from
Dr. Gamgee's account of his work in his PhijisioJ. Clirm. 427 H scq.ihe above description
<if protagon and lecithin is in great measui-e taken.

■* Banmstark, Zeif. 2'fii/siol. Chem. ix. 32i).

■' Thudichum, Bej). of Med. Officer of Privij Cuiuirll, 1.S74, p. 11:5 at seq.



■IIIK NKKVol s S^'STKM



Protagon

J*reparatiou. — When pounded hr.-iin is ti-«\ited with water, the
myelin swells up and is cxcocdiiifjly difficult to woi'k with. One of
the steps in Liebreich's original process for preparing protagon con-
sisted in treating it with water and ether, (.xamgee and Blankenhorn
found that this part of the operation could be dispensed with, and
their mode of preparing protagon is as follows : —

Fresh ox brain, freed fi-om blood and membranes as completely as
possilile, is digested for many liours in 85 per cent, alcohol at 45° C.
The Huid is filtered hot, and the process repeated with the residue so
long as the tiltrate when cooled to 0° C deposits a fair amount of white
precipitate. This precipitate is collected, and agitated with ether to
extract cholesterin. The residue is then dried in an exsiccator. The
resulting mass is powdered, moistened with water, digested for many
hours with alcohol at 45° C. and filtered hot. The filtrate is allowed
to cool gradually, and protagon separates from it in the form of rosettes
of microscopic crystals. It may be purified by recrystallisation.

The average percentage composition of this substance is as follows :



Elements


Gamgee and Blankenhorn


liaimistark


Calculatal from the fiirinula


C

H

N

P




66-39

10-69

2-89

1068

19-462


66-53
11-02

2-70

1-049

18-701


66-45

10-66 1

2-42

1-07
19-40



The average numbers in these three sets of analyses are seen to be
in remarkably close agreement. The empiiical formula calculated ])y
Gamgee and Blankenhorn from their results is C,6oH3QgN5P03^.

Alcohol and ether will not dissolve out lecithin from protagon ; it
is therefore not a mere mechanical mixture containing lecithin. It,
however, yields on treatment with alkalis the same products of
decomposition as lecithin does.

The relation of lecithin to protagon is a ])oint which has still to be
worked out.

Protagon is accompanied in the biaiii with substances which may
be provisionally termed cerebi-ins ; Ijut the cerebrin is not merely mixed
with lecithin as Hoppe-8eyler supposed.



526 THE TISSUES AND ORGANS OF THE BODY



Lecithin

Lecithin is not merely found in the uervous tissues, but ;ilso in the
following places : —

1. In yolk of egg. This was first described by dSobley ' as lecithin.
After Liebreich's discovery of protagon, Parke ^ described the chief
■phosphorised constituent of eggs as protagon also. Hoppe-Seyler •' and



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