l Dura mater - (pachymeninx) - dense fibrous CT; osteoblastic outside (skull), or mesothelial facing the epidural space (spine); specialized layer of dural fibroblasts* attaches dura to arachnoid.
2 Arachnoid complex - apposed to the dura is a layer of well attached cells, several cells thick; between this layer and the pia are open subarachnoid spaces, crossed by trabeculae of collagen, clad in other arachnoid cells, and supporting the vessels.
3 Pia mater - thin cellular, vascular and collagenous layer, adherent
to the BL of the nervous tissue.
(Arachnoid and pia comprise the leptomeninges.)
* The idea that the arachnoid was merely a membrane led to the mistaken notion that it had to be separated from the dura by a 'sub-dural space'. Such a space only arises by a forcible cleaving between the fibroblasts of the inner dura, as occurs in 'sub-dural' haematomas.
2 Ependyma and choroid plexus
Ependymal epithelium lining the ventricular cavities and canals of the CNS is simple, columnar or cuboidal. In regions of each ventricle, tufts of blood vessels (mainly fenestrated capillaries) project out from the pia, and are covered by a loose CT coat, then a layer of cuboidal ependymal cells on a BL. This choroid plexus forms cerebrospinal fluid (CSF) secreted into the ventricles.
These plexus ependymal cells have ion pumps, deep basal infoldings, and luminal microvilli.
3 Cerebrospinal fluid's return to blood
The subarachnoid space, which dilates into chambers, cisterns, fills with CSF spilled out of the ventricular system via the foramina of Lushka and Magendie in the fourth ventricle. Some CSF may come out of the brain tissue via spaces between blood vessels and the pia. CSF returns to the dural sinus blood through the thin walls of the arachnoid villi and granulations.
4 Blood-brain barrier
The blood capillaries serving the brain tissue have a characteristic structure of unfenestrated endothelial cells held together by tight/occluding junctions on a thick basal lamina, whose outer surface is enclosed by glial cell processes (astrocytes' pedicles). The endothelium has few transcytotic vesicles and is very selective in what it transports. In most regions of the brain the endothelium blocks the passage of most materials from the blood into the neural tissue, and a blood-brain barrier (BBB) is said to exist for such substances.
5 CNS elements
The two cells specific to neural tissues are the neuron/nerve cell and the glia cell, for the latter of which several varieties exist. Some of the glial cells are used to form a layer - glia limitans - separating neurons from the numerous blood vessels and the enclosing pia matter.
_ | dendrites | (receptive) l Cell with soma and extended processes -----| | axon |_ (transmissive)2 Axon may or may not be myelinated. It may or may not give off collaterals, sometimes recurrent back to near the soma.
9 When a neural area has such a variety of cells, the Golgi and other
methods to be described later are used to discover:
(a) how the various cells are interconnected (intrinsic connections);
(b) how projections of nerve fibres from outside and to outside the nucleus or brain area terminate or originate (extrinsic connections).
2 Glial functions
l Myelination of myelinated axons (oligodendrocytes).
2 Augmenting the extracellular space, e.g., being an active compartment for ionic buffering by taking up and redistributing K+, and metabolizing transmitters (astrocytes). The CNS has little true tissue space and no lymphatics.
3 Helping to induce endothelial cells to create the blood-brain barrier (astrocytes).
4 Insulating chemical and electrical events from nearby sensitive structures (astrocytes and oligodendrocytes).
5 Storing glycogen and passing on raw materials for the energetic and synthetic processes of the neuron (astrocytes).
6 Acting as macrophages to remove degenerating nerve cell components (microglia).
7 Protecting neurons by metabolising excess ammonia from liver disease (astrocytes).
8 Mechanically supporting the neuronal elements and keeping them properly spaced (astrocytes and oligodendrocytes).
9 Transient radial glia guide the migration of developing neurons.
3 Some evidence for cell types performing these functions
l Oligodendroglia contain myelin basic protein. Their membranes are connected with myelin lamella that they form.
2 Excluding myelin, insulation is a task of astrocytes whose processes enfold synapses and neural membranes.
3 Astrocyte cytoplasm also could serve as a nutritive pathway via its pedicles and processes from the blood capillary wall to the neuron, and can transfer ions and inactivated transmitters in the reverse direction.
4 Fibrous astrocytes have long processes, firm connections with one another and very little in their cytoplasm but filaments and glycogen. They would seem to be fitted for the role of mechanical support.
4 Myelination process
l Many axons remain unmyelinated throughout their existence. However, for rapid saltatory (jumping) nerve conduction a myelin sheath interrupted by nodes is necessary. This sheath is a modified lipoprotein membrane, rich in cerebrosides and other special lipids and proteins.
2 The process of myelination in peripheral fibres is by an apparent 'rotation' of the Schwann cell in relation to the axon that it has enfolded, thus enclosing the axon in many layers of Schwann-cell membrane. These membranes fuse together, but the lamellar structure remains visible in EM, and an outer mesaxon connects the last wrapping to the Schwann cell's own plasmalemma.
One Schwann cell myelinates a given length of axon, which is separated by an unmyelinated node of Ranvier from the next myelinated segment. Outside the Schwann-cell or neurolemmal sheath lies a basal lamina, beyond which are found the collagen fibrils and fibroblasts of the endoneurium.
3 In the CNS, the oligodendrocyte incrementally adds membranes to several axons, and to more than one segment per axon. This myelin configuration is compatible with 'spiralling' membrane synthesis, but not actual rotation. Nodes are present, but not as distinct as in the PNS.
4 Myelination takes place in different tracts of the brain at different times during development. The time of myelination correlates fairly well with the development of the ability to function in that system.
5 Remyelination (successful or attempted) is involved in the mature nervous system in two circumstances - the regeneration of peripheral nerve fibres, and demyelinating diseases in the CNS and peripheral NS.
l Types of synapse
l Axosomatic: to the neuron's body.
2 Axodendritic: e.g., from climbing fibres to Purkinje cells' dendrites.
3 Axodendritic to spines, e.g., from parallel fibres to Purkinje cells' dendritic spines. (The presence of spines on dendrites is used to subclassify neurons in many brain regions.)
4 Glomerular: a rounded structure serving several dendrites, e.g., from mossy fibres to cerebellar granule neurons.
5 En passant: made 'in passing' on the way to other synapses.
6 Axo-axonic: synapse onto another synapse or the axon's initial segment (for presynaptic inhibition).
7 Reciprocal dendro-dendritic: e.g., in retina and olfactory bulb.
2 Synapses also differ in the number, size and density of their vesicles, in
the transmitter and neuromodulator substances that these hold, in the
organelles present, and in the cleft material and membrane densities.
3 Chemical neuroanatomy involves mapping which connections of the CNS employ particular neurotransmitters, e.g., serotonin, acetylcholine, dopamine, etc.
2 Cerebellar and cerebral cortices
Differ from the spinal cord in these ways: (a) grey matter lies to the exterior with white underlying it; (b) tissue of both kinds of cortex is folded: into gyri for the cerebral cortex and folia in the cerebellum; (c) nerve cells are of various types and are disposed in layers parallel to the pial surface, thus
l Cerebellar cortex (Pia). l Molecular layer (cell processes, but few cells). 2 Purkinje cell layer. 3 Granule cell layer (densely packed small neurons) (underlying white matter).
2 Cerebral neocortex (Pia). l Molecular layer. Layers 2, 3, 4, 5, 6 with varying proportions of stellate, fusiform and small, medium, and large pyramidal cells (white matter).
The number of layers to be clearly seen depends on the particular area of the cerebral cortex and the criteria of the investigator. Thus Cajal worked with an 8-layered scheme, whereas Brodmann adopted 6 - today's choice. Even so, in the motor region only 5 are to be easily made out.
3 Divisions of the cerebral cortex
3 Brain stem
(a) Resembles the spinal cord in having nerve cell bodies grouped in nuclei and nerve fibres in tracts.
(b) Some special nuclei of the brain stem and hypothalamus are:
... (i) The reticular formation is an extensive system of groups of neurons serving many vital tasks, but whose nuclear organization is hard to discern.
... (ii) Neurons of the substantia nigra contain melanin pigment and dopamine.
... (iii) Certain hypothalamic nuclei have neurosecretory neurons.
Fig. 4 Neuronal degeneration (with changes used earlier in tracing neural pathways)
/ / 0\/ Next neuron in the chain | SEVERANCE . \ may display a trans- | or . \ neuronal atrophy / \ CRUSHING . /\ / * \ ! . / * \ __ / OO *\ ! . /* NN \ _______ \*OO /------------------------------! - - - - - - - - - - - - . . . . . 0\* NN*/ \ * / Proximal fibre stump | \* */ \ / remains relatively intact Entire distal segment 0\/ | for a while experiences a Wallerian | | degeneration: | | | | 1. Fibre breaks up into fragments Terminal changes occur in Nerve cell soma exhibits 2. which become osmiophilic (Marchi the synapses - bouton a loss of Nissl substance* - reaction) & argyrophilic (Fink-Heimer changes - before they too retrograde cell reaction reaction) are resorbed with swelling & recovery, 3. and are later removed by glial if this distance........................! phagocytosis. Absence of the fibres is not too short; otherwise, can then be revealed by silver or the reaction becomes a myelin methods for normal fibres. progressive atrophy, and the cell disappears to be replaced by glia (i) Retrograde cell reaction shows from where the damaged fibres have come (ii) Wallerian degeneration of the fibres shows their course through the CNs (iii) Bouton changes 0 and degeneration in the fine preterminal branches . . . indicate whereabouts the fibres of the tract terminate
2 Regeneration in the peripheral nervous system .
l This requires a two-sided effort, but not symmetrically two-sided as in other tissues' healing.
2 On the distal side of a cut through a nerve, macrophages and Schwann cells remove the degenerating axons and myelin, and Schwann cells proliferate and organize themselves to keep open the endoneurial tubes.
3 On the proximal side the axon degenerates back a little way and forms a retraction bulb, from which many fine axonal branches sprout.
4 The energy and synthesizing capacity for this new axonal material reside in the intact nerve cell body.
5 The soma to do this has to disperse its Nissl substance in order to form proteins; the cell swells and the nucleus may move off centre.
6 This change in the Nissl substance is termed chromatolysis, part of the retrograde cell reaction.
7 Some of the axonal sprouts find their way down the endoneurial tubes, aided by the Schwann cells' keeping out fibroblasts,
8 and may eventually re-innervate old end-organs or develop new ones.
9 Some new axons will be myelinated by their Schwann cells.
10 The pace of peripheral fibre regrowth is that of slow axonal transport - about 2 mm per day.
3 Regeneration in the CNS
l The lack of endoneurial tubes and a different kind of glial cell responsible for the fibres lead to the formation of a 'scar' of glial cells, leucocytes, and extracellular matrix, blocking any effective regeneration by the axonal sprouts.
2 The glial cells release factors inhibiting axonal growth and guidance.
3 Also, the axonal lesion results in a greater degree of 'shock' to the neuron soma, which may undergo a progressive atrophy to the point of disappearance, i.e., a loss of neurons may follow.
4 Their place is taken by numerous glial cells, constituting a gliosis.
4 Pathway tracing and neural degeneration
l Some fibre tracts can be seen to originate from or to enter particular brain nuclei. However, it was usually impossible to decide from a histological examination of a normal tract where its fibres have come from, and where they are going. This pathway information was learned by taking advantage of the special degenerations seen in the nerve cell and its fibre, when they are severely injured (Fig. 4). (Nerve cell is often used loosely to refer to the nerve cell's soma.)
2 Pathway-tracing procedure
3 Recent pathway-tracing methods are based on axoplasmic transport (which
takes place in both directions).
(a) Radioactively labelled leucine injected near the soma is carried by orthograde transport to the axon terminals of the neuron, where it can be revealed by radioautography (Chapter 30.E).
(b) Horseradish peroxidase injected in the vicinity of the axon terminals is transported retrogradely back into the neuron's soma. The HRP accumulates in, and can be used to mark, those cells projecting to the site of injection.
Table 4. Applications of histological staining methods for central nervous system
For the normal CNS