Studies in the Osteopathic
The Nerve Centers: Volume
Louisa Burns, M.S., D.O., D.Sc.O.
THE STRUCTURE OF THE NEURON
The nervous system has been grossly divided into various parts, such as
cerebrum, cerebellum, spinal cord, ganglia, and so on. This gross
division is convenient for purposes of study, but it must be remembered
that it does not represent any logical classification of the parts of the
nervous system. Any separation of one of these parts from its fellows
can be accomplished only by cutting through numbers of fibers which belong
to the cell bodies of other and often distant parts of the nervous system.
The Neuron Theory
The units of which the nervous system is composed are neurons and the tissues
which nourish and support them. The unity and independence of the
neuron has been demonstrated. This is called the “Neuron Theory,”
that is, that the neuron is structurally and physiologically an individual,
preserving its identity throughout life. It is not capable of independent
existence. It has, after a very early period of embryonic life, no
power of reproduction; throughout life it requires for its nutrition very
complex substances which must be formed by other tissues of the body.
It is thus an extremely specialized cell, though it is as independent,
as individual, as much a structural and functional unit as is the cell
of the liver or of the blood. It seems also true that each neuron,
or at least each group of neurons, is specialized, doing its own work and
none other; unable to perform the duties of other neurons, as they are
unable to perform its duties. As the death of persons of unusual
ability leave work long undone, so the injury or death of these highly
specialized cells leave undone those duties for which they were especially
external form of neurons varies greatly. (Fig. 1.) The embryonic
cells are spherical. By the outgrowths of the axon and dendrites
the shape assumes many variations, many of them very complicated.
processes of the neuron include dendrites and axon. Within the protoplasm
lie various deutoplasmic substances. The nucleus, in the adult normal
neuron, lies near the center of the cell body. All of these structures,
while in the main resembling similar structures of other cells, yet present
The nucleus varies in size both absolutely and relatively to the size of
the cell body. Throughout the nervous system two chief classes of
cells are to be found, depending upon the size of the nucleus and the cell
body. This classification is given by Nissl.
whose nuclei are large, lying within a scanty ring of protoplasm, are called
“karyochromes.” They resemble embryonic cells, though they may be
found during life. The karyochromes have deeply staining nuclei,
with the nucleoli rather poorly defined. The protoplasm is very scanty,
contains no tigroid masses or pigment, and has no very well defined reticulum.
The nucleus may be eccentric. The cell has no well defined axon or
dendrites, but may have one or two short prolongations, not to be distinguished
as either axon or dendrite. The function of the karyochromes is not
are of larger size, with nuclei relatively small, lying in the midst of
a large mass of protoplasm. Probably the functional part of the nervous
system is composed of somatochromes. The somatochromes have nuclei
which stain feebly and with difficulty. Their nucleoli stain deeply
and are well developed. Both the nuclear and the cytoplasmic reticulum
are well defined. The protoplasm surrounds the nucleus about equally
on all sides in normal cells. The axons and dendrites are variously
developed, becoming of great length in some cases. The cell body
and the dendrites contain tigroid masses and pigments in amounts varying
with the class of the cell, its place in the nervous system, and its physiological
conditions, such as rest, nutrition, age, etc.
nucleus is permeated by a chromatin network, with knots at the intersections.
This network contains within its meshes one nucleolus which stains very
deeply and is always—or seems to be always—present. Besides this
nucleolus there may be from one to four others, which are sometimes called
supernumerary. These stain less deeply and often variably, and they
may vary greatly in size as well as in numbers. These supernumerary
nucleoli may be simply rather large net-nots.
centrosome is not found in the neuron after it has reached a stage of development
sufficient to render its recognition possible—that is, after it has passed
the possibility of reproduction. A few observers have reported centrosomes
in the nerve cells of adult brains in the neighborhood of injuries, but
these findings have not been substantiated by later studies. It now
seems probably true that the later divisions of the neuroblasts were of
such a nature as to give the structures concerned in initiating division
to the cells which become developed into neuroglia, while the cells which
become developed into neurons are thus left without the power of reproduction
but with enormously increased possibilities of differentiation along the
lines of irritability and conductivity. Later investigators report
the centrosome present in sympathetic cells at a later time.
function of the nucleus in the neuron is of the same nature as in other
cells. It controls the nutrition of the neuron throughout its whole
extent. In the case of the cells of the sensory ganglia of the lumber
cord, the peripheral prolongation may be, in a tall man, more than a meter
in length, while the centrally directed axon is about equal in length.
The nucleus of these cells, placed about midway of the whole length of
the neuron, controls the nutrition of the whole.
cytoplasm of the neuron is of extreme complexity. The spongioplasm
is composed of rows of granules which stain with varying degrees of intensity.
The fibrils of the spongiaplasm extend into the dendrites and beyond the
limits of the hyaloplasm, and similar fibrils extend into the axon.
The axonic fibrils stain in a manner slightly different, but by some neurologists
are considered continuous with the spongioplasm of the cytoplasm.
In the meshes of the spongioplasm lie the hyaloplasm and certain deutoplasmic
bodies. The hyaloplasm is a homogeneous, viscid substance, which
stains very feebly with the protoplasmic dyes. Very little is known
of its structure or function.
The Tigroid Substance
tigroid masses, or Nissl’s substance, or chromophilic granules, as they
are variously called, lie in the meshes of the spongioplasm of the cell
body and the proximal part of the dendrites, but not in the axon or in
the axon hillock. (Figs. 1, 2, 3.) These bodies are usually
found only when the nerve cells have been fixed very rapidly and stained
in a certain manner. Intravitam staining does not demonstrate them
clearly, though sometimes they may appear faintly. For this reason
it is supposed that they do not exist as such during life, but that the
appearance is a post-mortem phenomenon. It is, however, a very constant
and valuable phenomenon, since the appearance of the tigroid substance
changes very profoundly during fatigue, poisoning, or disease. The
tigroid substance differs chemically from the other neuron structures.
It is not soluble in dilute and concentrated acids, boiling alcohol, cold
or boiling ether, or chloroform, and it resists the action of pepsin-hydrochloric-acid
longer than do other cell structures. It can be dissolved from the
cell, leaving the cytoplasm intact, by the use of concentrated solutions
of lithium carbonate. These masses contain iron, phosphorus and the
nuclein bases in about the proportions of nuclear material.
Fig. 1. Cell from hippocampus of kitten.
Fig. 2. Cells from dentate nucleus of woman
about 30 years old. 800 diameters.
Fig. 3. Sensory ganglion cells. Human
embryo of about 5 months. The outlines of the tigroid masses are
shown more clearly than on the slide.
masses are composed of fine granules imbedded in some coagulum-like material.
They are usually angular in outline in the normal adult cell. Similar chromophilic
masses are to be found in the nerve cells of invertebrates, even those
of rather a low type, such as snails, molluscs, etc.
abnormal neurons, those fatigued, poisoned, or affected by certain conditions
of disease, the tigroid substance shows very pronounced changes from the
normal. (Figs. 4, 5, 6, 7.) At an early stage of fatigue the
masses are found to have rather rounded outlines and to stain less deeply.
Later they are found smaller, with even less vigor in staining. With
exhaustion, the masses are not to be found, and the cytoplasm of the nerve
cells takes a faint blue tint, with perhaps here and there very fine particles
with the deeper stain. Under the influence of poisons, excessive
heat and certain diseases the variations in the size and staining of the
tigroid masses are very characteristic. This matter is discussed
at length in Barker’s “Nervous System.”
the tigroid substance shows these constant changes, since it becomes dissipated
during cell activity and becomes restored during rest, it is supposed that
it represents the reserve of cell energy. It is not known whether
the disappearance of the tigroid substance is due merely to a mechanical
separation of its particles, or whether it is actually used up during cell
activity. Since the masses are rebuilt in a remarkably short time,
it must be true either that they are simply separated during activity and
reunited during rest, or that the materials of which they are composed
are very rapidly built up from the lymph surrounding the nerve cell.
In certain tests they have been found to be restored to their normal appearance
within twenty minutes.
Fig. 4. Sensory ganglion cells of adult
dog. The nerves from this ganglion had been stimulated by electricity
at intervals of about ten minutes during anesthesia and before death.
The vacuolated protoplasm, shriveled nucleoli, swollen and shriveled nuclei,
large pericellular lymph spaces, disintegrated tigroid masses, show effects
of excessive fatigue. 380 diameters.
Fig. 5. Cells from cortex of woman with
cerebral abscess. Tigroid masses disintegrated, nuclei swollen or
shriveled, cell body swollen, dendrites of irregular contour. 175
Fig. 6. Large and small pyramidal cells
from somesthetic area of woman with abscess in temporal lobe of same
side. Swollen cell bodies, thorn-like dendrites, eccentric nuclei, chromatolysis,
swollen and shriveled nuclei, show effects of abnormal conditions.
The small granules are yellow pigment. 175 diameters.
tigroid masses persist in remarkable manner during certain disease processes.
In a section from a brain containing an encysted bullet and an abscess,
together with numerous small foci of infection, there are often found cells
closely adjacent to the abscess and the inflamed areas, and to the bullet
cyst, which contain many fairly normal tigroid masses, while in the same
section, not more than the diameter of the cell distant from those with
normal tigroid substance, are found others with every appearance of severe
degeneration, and with a total absence of the tigroid masses.
The Yellow Pigment
The yellow pigment is another of the dentoplasmic substances of the neuron.
This substance occupies certain restricted areas in the cell body.
(Figs. 5, 6, 7.) The pigment is composed of rather coarse granules,
which are of a light yellow color. It is not dissolved by ether,
oil, alcohol, or water; it is not affected by any of the dyes usually used
in preparing neurological material. It is stained with osmic acid
if it has not been acted upon by ether or alcohol. It is not identical
with the pigments of substantia nigra, locus ceruleus, etc.
pigment is not found in embryonic material. In the human nervous
system it is first found in the spinal ganglion cells of the child of about
six years of age. At nine it is found in the motor cells of the cord.
Later it is found in the brain and all through the central nervous system.
It is not described as occurring in the cells of the sympathetic system.
Under abnormal conditions, as in general paresis, or in premature senility,
or in the presence of brain lesions, the amount of the pigment may be enormously
increased. It may occupy practically the whole of the cell body,
leaving the nucleus half extruded. Sometimes the cell leaves no trace
of its existence save that the mass of yellow pigment shows the outline
of the cell as it appeared during its life. (Fig. 8.)
Fig. 7. Cells from somesthetic area of
cortex of woman with cerebral abscess.
Fig. 8. Cells filled with yellow pigment
granules. From nucleus of the reticular formation of woman with abscess
in temporal lobe.
Fig. 9. Purkinje cell, kitten, half-grown.
Fig. 10. Pyramidal cell from human cortex.
Fig. 11. Pyramidal cell from cortex of
facts known in regard to the yellow pigment present this substance to us
as if it were an insoluble waste product of nerve metabolism. If
there were some substance, insoluble in the fluids of the body, and formed
in very small amounts during a lifetime, such a substance would vary in
amount and distribution as the yellow pigment varies.
pigments are found in the bodies of the neurons of the substantia nigra,
the locus ceruleus, etc., but these seem to be constant during extra-embryonic
dendrites, as their name indicates, resemble trees. This resemblance
is very beautifully shown in the Purkinje cells of the cerebellum.
(Fig. 9.) They are protoplasmic prolongations of the cell body, and
they have the same staining reactions as the protoplasm of the cell body
itself. These branches originate as outgrowths of the cell body.
They have broad bases and usually lose in diameter during their length.
(Fig. 10.) They branch at acute angles, like the branches of trees,
and they exhaust themselves sometimes through frequent branchings.
They are usually quite short, and do not leave the vicinity of the cell
body. In the case of the sensory neurons of the first order, however,
the dendrites attain enormous length, assume a medullary sheath and neurilemma,
and are not to be differentiated, structurally and in adult life, from
Fig. 12. Cell from hippocampus of kitten.
The cortex had been stimulated by electricity during anesthesia before
death. 100 diameters.
Fig. 13. Multipolar cells from medulla
of cat. 40 diameters.
Fig. 14. Cells from corpora bigemina of
crow. 175 diameters.
Fig. 15. Polymorphic cells from medulla
of adult guinea pig.
Fig. 16. Cells from seventh layer of new-born
baby’s brain. A, axon.
Fig. 17. Anterior horn cell, with peri-cellular
basket. 475 diameters.
Fig. 18. Basket around Purkinje cell.
Human, adult. 470 diameters.
dendrites within the central nervous system are often found studded with
small budlike protrusions called “gemmules.” (Fig. 11.) It
is not certainly known whether these gemmules are an artefact or whether
they represent a normal structure of the neuron. In certain diseases
of the nervous system, particularly the brain, these gemmules are found
greatly swollen and of irregular outline and position. (Fig. 12.)
Sometimes they do not appear at all in normal brain material; sometimes
they are found plainly in equally normal material. Their nature is
thus unknown at present.
contain the tigroid substance, as does the body of the nerve cell.
Dendrites rarely contain the yellow pigment granules.
function of dendrites is not certainly known. There is some reason
for supposing them to be partly nutritional in function. Nerve cells
are unusually large. The surface of the cell body, that is, the possibility
of absorbing nutrition and of excreting wastes, is proportionately small
in comparison with the mass of the cell, that is, with its need of nutrition
and its formation of waste material. This relation seems the more
striking and fatal when it is remembered that the metabolism of the neuron
is of an extremely rapid and vigorous order, and that its activity is so
complex that there is great need for the most speedy renewal
of the nutrition and most speedy removal of its wastes. Now by means
of the forest of finely-branching dendrites the total surface area of the
cell body is greatly increased, and the facilities for the absorption of
nutrition and for the removal of wastes is correspondingly increased.
There seems very little doubt that this is one important function of the
dendrites of the cell. (Figs. 13, 14, 15.)
are known also to carry cellulipetal impulses. Morat insists upon
the “polarity” of the neuron—the fact the impulses reach the cell body
by means of the dendrites and leave it by means of the axon. This
polarity is very well demonstrated in the case of certain neurons.
important structure of the neuron is the axon. It is probable that
the neurons of the higher vertebrates, at any rate, possess only one true
axon, though the sensory neurons of the first order have two processes
which are very much alike. Physiologically, however, even these processes
differ, since the peripheral prolongation carries cellulipetal impulses;
and this process contains the tigroid substance during its early development.
In other parts of the nervous system the mon-axonic nature of the neuron
axon arises from a part of the cell body which contains no tigroid substance.
(Fig. 6.) During embryonic development and throughout life
the absence of the tigroid substance in the axon and in the neighboring
protoplasm is constant. This space around the origin of the axon
is called the “axon hillock” or “implantation cone.” It may be placed
almost anywhere upon the surface of the cell body, or upon any of the larger
dendrites near the cell body. (Fig. 16.)
axon retains its diameter throughout almost or quite its entire length.
It may give off branches called “collaterals,” which arise at a right angle
to the axon, or may assume a somewhat recurrent direction. Neurons
are classified by Golgi according to the form of the axon. Cells
whose axon is long, and passes into the white matter, are called by him
“Type I” cells, while those whose axons are short, giving off many very
short collaterals which ramify extensively in the immediate neighborhood
of the cell body, are called “Type II” cells. It is evident that
Type I cells are concerned in relating parts of the nervous system which
are more or less distant from one another, while the Type II cells bring
into relation those neurons which are placed very near one another.
spongioplasm of the axon and the axon hillock seems to be continuous with
the spongioplasm of the cell body itself. The axon contains fibrils
which differ somewhat from those of the cell body and dendrites in staining
reactions, though they seem to be more or less continuous with them.
vary in length from the few microns of the Golgi cell of Type II to the
meter or more of the axons of the large cells in the anterior horn of the
lumbar cord, which terminate in the muscles of the feet, or the axons of
the lumbar sensory ganglion cells, which terminate in the nucleus gracilis
in the medulla oblongata. The nutrition of the axon, in all its extreme
and attenuated length, is dependent upon the integrity of the neuron as
a unit. As in every other cell, once any part of the protoplasm is
severed from the nucleus, that part soon becomes degenerated and dead.
In the case of the long axons the mass of the fiber may be two hundred
times the mass of the cell body, and yet the small cell body with its nucleus
controls the metabolism of the axon to its farthest extremity.
axon carries cellulifugal impulses, that is, it carries the nerve impulses
from the cell body to other neurons, or to the axon terminations in muscles,
axons in the central nervous system are surrounded by the myelin sheath,
or medullary sheath, or the white substance of Schwann, as it is variously
called. This is a white, homogeneous substance of a fatty nature,
and it surrounds the axon in sufficient quantities to make the area of
a cross section of the sheath equal to the area of the cross section of
the axon which it encloses. This myelin substance gives the characteristic
white glistening appearance of the so-called “white matter” of the brain
and spinal cord. The olfactory axons alone of the cerebro-spinal
nerves are non-medullated. Axons become medullated in the order of
their functional development, though it is not known whether beginning
function precedes or follows the medullation of the axons. The axons
of the sympathetic neurons have either no medullary sheath or extremely
thin ones, in mammals. In birds the sympathetic axons are usually
of the central nervous system the axon has another coat, the neurilemma.
This is a sheath composed of connective tissue cells, greatly flattened
and applied very closely to the medullary sheath. At intervals of
about seventy-five times the diameter of the nerve fiber the medullary
sheath of the peripheral nerves is interrupted by a circular constriction
which permits the neurilemma to lie in contact with the axon itself.
These interruptions are called the “nodes of Ranvier.” The neurilemmal
sheath between one node of Ranvier and the next contains one nucleus, and
is thus supposed to be derived from a single connective tissue cell.
function of the medullary or myelin sheath is not known. It has been
supposed to act as a sort of insulator, as a protection to the nerve fiber,
as a source of nutrition to the nerve fiber, but there is no sufficient
evidence in favor of any of these views.
neuron is a cell and has the structure characteristic of all cells.
It is also a highly differentiated cell, and has, in addition to these,
the structures adapted to the performance of these specialized functions.
The neuron consists of a cell body together with its prolongations, its
axons and dendrites. The cell body varies from four to one hundred
and fifty microns in diameter. The form of the cell varies according
to the number, position and size of the dendrites. The existence
of a cell wall is problematical. Several authors describe a cell
wall of extreme tenuity, others deny its existence. The extension
of the spongioplasm into the intercellular gray substance, described in
the section on Relations of neurons, seems to be evidence against the presence
of the cell wall.
peripheral prolongations of the sensory nerves and the axons of the motor
nerves are alike called “axis cylinders.” The structure of the sensory
fiber of the adult is not to be distinguished, histologically, from the
motor axon. In the ordinary nerve trunk the two classes of fibers
are intermingled with the fine, non-medullated sympathetic axons (fibers
of Remak) to make what is called the “mixed nerve.”
nerve trunk is enclosed by the “perineurium” and is divided more or less
completely into bundles by the “endoneurium” and the epineurium,” of all
which are connective tissue sheaths for the support of the nerve fibers
and their vessels. The strength of the nerve fibers depends upon
the toughness of these connective tissue sheaths.
coverings of the nerve fibers, together with the fibers themselves, are
nourished as are other tissues, by blood vessels and lymphatics.
These are subject to variations in size, according to changes in the systemic
blood pressure, and they are innervated by vaso-motor nerves, as are most
of the blood vessels of the body. Thus the nerve trunks are subject
to hyperemic and ischemic conditions as a result of abnormal vaso-motor
impulses, as are other tissues and organs.
addition to the etiological factors of neuralgia and neuritis which are
already fairly well known, the place of such circulatory changes must be
the neuritis of a severe form is usually due to alcoholism, lead, or some
other chronic poisoning, the milder types and the neuralgias are often
caused by the same structural abnormalities found to be efficient causes
of hyperemias and congestions in other tissues, i.e., slight malpositions
of vertebrae or ribs, abnormally contracted muscles, reflex irritation
from other organs of the body, including the various sources of peripheral
irritation, and by the poisons resulting from the retention of the autogenic
wastes, or from the use of drugs.
the neurilemma is continuous with the sheaths of the sensory ganglia, and
since these also are nourished by the blood vessels and lymphaticss, themselves
innervated by vaso-motor nerves, it is evident that the same abnormal conditions
may bring about pain and hyperesthesias due to the ganglionic condition
and not associated with motor or vaso-motor disturbance. Such cases
are very resistant to ordinary methods of treatment; drugs only purchase
temporary relief at the expense of greater pain later. In such cases
the correction of the structural abnormalities may permit the normal circulation
to be established, and recovery must follow in the degree possible to tissues
which have been more or less injured, not only by the original cause of
the disturbance, but by the efforts to reduce the pain.
effects of separation from the nucleus are very well shown in the phenomena
of Wallerian degeneration, so called after Waller, who gave the first exact
description of the condition. When any nerve fiber is cut, the part
which is separated from the cell body undergoes a series of changes whose
sum is called by this name. The nerve fiber itself begins to show
the change within a few hours after section. The fiber becomes granular
in appearance, the granules increase in size, and undergo fatty degeneration.
The medullary sheath becomes degenerated into droplets, at first very small
but increasing in size. These structures are absorbed, probably in
part by the lymphatics and veins, and in part by being used as food by
surrounding tissues. The neurilemma cells, which are, of course,
not injured except at the very point of section, begin to multiply very
rapidly. This multiplication may be due in part to the presence of
the increased food supply, but is more probably due to the irritation of
the disintegrating nerve fiber and myelin. If regeneration does not
occur, these neurilemma cells die and are themselves absorbed. The
rapid multiplication of the neurilemma cells produces a solid cord of connective
tissues of an embryonic type. The center of this cord, perhaps because
of pressure, perhaps because of the lack of nutrition, contains no nuclei.
This central portion is called the “band fiber.”
normal conditions, following section of a nerve trunk, regeneration occurs.
The conditions most favorable to regeneration are important.
ends of the injured nerve should be brought as closely together as possible,
and should be sewed together.
structures to which the nerve is distributed must be kept in as nearly
as possible a normal condition. This is best secured, in the case
of the muscles, by massage and by electrical stimulation, applied with
care. In the case of the skin, for the sake of sensation, the massage
is most helpful.
general health of the patient must be kept as nearly perfect as possible,
and his attention should be directed to the paralyzed part of the body.
The descending impulses from the cerebrum seem to stimulate the cells in
the cord which are in closest relation to the injured fibers by the attentive
attitude and the efforts toward movements, and regeneration seems to be
somewhat facilitated in this way.
occurs most readily and most completely in patients who are young and in
process of regeneration follows the course which is to be expected from
the physiological conditions. The process of degeneration affects
the central end of the stump for a distance of one or several segments.
At the upper limit of the area of degeneration the stump of the nerve fiber
becomes swollen and bulbous. From this bulbous extremity several
fine fibers shoot out, directed peripherally. These fibers are of
variable size. One of them soon attains a certain superiority, and
the others become atrophied and lost. The remaining fiber grows toward
the periphery at a rate approximating a millimeter a day, penetrates the
“band fiber” formed by the parenchymous cells of the multiplying neurilemma,
and ultimately makes connection with the structures originally innervated
by the injured nerve.
In its essential
features the process of regeneration of nerve fibers follows the same biological
laws which govern the process of regeneration in all living structures.
There is nothing beyond the normal conditions which can add to the completeness
of the regeneration nor increase the rate of the growth. No drug or stimulant
can be used advantageously, nothing can be done which is of the least benefit
except to give the growing fibers the rest which they had during their period
of most rapid growth, and to keep the muscles and the sensory structures in
as nearly as possible their normal condition.