Peripheral Nerves And Nerve Tracts

 

Professor Alfred Cuschieri

Department of Anatomy, University of Malta.

 

Objectives

On completion of this unit the student should be able to:

 

* Distinguish between nerve fibres in the central and those of the peripheral nervous system

* Explain the structure of the myelin sheath

* Name the locations of unmyelinated nerve fibres

* Describe the changes that accompany nerve injury and regeneration

* State the conditions that affect nerve regeneration

* Interpret the consequences of damage to various parts of the nervous system and which of them would be potentially recoverable.

 

 

The White matter and Peripheral Nerves

The white matter in the central nervous system is formed of nerve tracts, which consist of:

- Mainly myelinated nerves of various diameters

- Oligodendrocytes

- Fibrous astrocytes

- Occasional microglia

 

Peripheral nerves consist of:

- Myelinated or unmyelinated nerve fibres

- Schwann cells

- Connective tissue forming the

 

There are two types of nerve fibre:

Myelinated nerve fibres

These consist of:

- A central axon

- A myelin sheath

 

The myelin sheath is interrupted at intervals by nodes of Ranvier.  The segment of myelin between one node and another is an internode, and is formed by:

- A Schwann cell in the peripheral nervous system – one Schwann cell forms an internode

- An oligodendrocyte in the central nervous system – one oligodendrocyte forms the internodes of several axons

 

Stages in the formation of myelin:

- An axon invaginates into a Schwann cell cytoplasm, suspended in it by a mesaxon (two layers of plasma membrane)

- The mesaxon elongates and spirals around the axon, each turn forming a lamella of myelin

- The cytoplasm and extracellular space between each turn of mesaxon are reduced to a minimum, and very closely packed

 

In the fully formed myelin, each spiral lamella consists of

A major dense line (dark line) formed by the closely apposed cytoplasmic faces of the plasma membrane, and measuring 2.5nm thick

A minor dense line (pale line) formed of the closely apposed external faces of the plasma membrane, and measuring 10 nm thick

 

At the node of Ranvier

- The axon is devoid of myelin and is covered by a glycoprotein coat (glycocalyx), rich in sialic acid

- The lamellae of myelin end on the axon in a staggered fashion

- The ends of the lamellae are distended by a small amount of cytoplasm replacing the major dense line

 

Schmidt-Lanterman clefts or incisures:

- Occur at intervals along the myelin sheath

- Appear under the light microscope as “clefts” in the myelin

- Are formed by a small amount of cytoplasm replacing the major dense line between the lamellae

- Maintain cytoplasmic continuity of the myelin with the  Schwann cell or oligodendrocyte. 

- Are spirally oriented for convenience of packing, to even out the bulges formed by the concentric turns containing cytoplasm.

2. Unmyelinated nerves

 These consist of axons that are invaginated into a Schwann cell or oligodendrocyte.  Unmyelinated nerves are the smallest nerve fibers with a diameter of 1mm or less

In the CNS unmyelinated nerves are very few and probably restricted to small internuncial neurons with short axons.

In the peripheral nervous system unmyelinated nerves occur at three main sites:

a)     the axons of post-ganglionic neurons of the autonomic nervous system, in which several axons invaginate individually into a Schwann cell, and each axon is surrounded by a mesaxon

b)     olfactory nerves in which bundles of axons are invaginated into the Schwann cell cytoplasm, and a whole bundle shares a common mesaxon

c)      some sensory nerves subserving pain and temperature 

 

 

Classification of Nerve Fibers

Nerve fibers are classified according to fiber diameter, which is also related to conduction speed and functional location.

Type
Diameter
Conduction speed

Location

A fibers

 

 

 

      a

12-20 mm

70-120 m/sec

Skeletal muscle; Pyramidal tract

       b

5-12 mm

40-70 m/sec

Discriminatory touch; Vibration

       g

3-6 mm

10-50 m/sec

Muscle spindles

 

       d

2-5 mm

6-30 m/sec

Pain & temperature; Touch

 

 

 

 

B fibers

1-3mm

3-5 m/sec

Pre-ganglionic autonomic

 

(myelinated)

 

 

 

 

 

 

C fibers

0.5-1mm

3m/sec

Post-ganglionic autonomic; Olfactory;  Pain

 

(unmyelinated)

 

 

 

Degeneration and Regeneration of Neurons and Nerve Fibers

This is a topic of major importance in neurology for two reasons:

1.     Experimental

- Experimentally-induced  degeneration was used extensively to map out the nuclei and nerve tracts in the central nervous system and their connections

- Damage to nuclei and following nerve tract to their terminations

- Damage to nerve tracts and observing chromatolysis in nuclei

2.     Practical

- Degenerative diseases of the nervous system, whether involving neuronal cell bodies or their axons constitute very important diseases, causing severe disability

- Trauma to the nervous system involves nerve and neuronal degeneration.  Their capacity to regenerate depends mainly on whether the lesion is in the peripheral nervous system, where recovery is possible, or in the CNS, where regeneration does not occur.

 

 

Following nerve injury at a point along the axon, the following changes occur:

1        Wallerian degeneration occurs from the first node of Ranvier proximal to the lesion to the nerve terminations.  This involves:

a.      Axons becomes oedematous

b.     Axons become fragmented

c.      Schwann cells round up and detach from the myelin sheath

d.     Myelin becomes fragmented

e.      Fragments are cleared up by macrophages in the peripheral nervous system, or by microglia in the case of the CNS

2        Chromatolysis occurs in the neuronal cell bodies.  This involves:

a.      The Nissl granules (RER) become fragmented and dispersed

b.     The neuronal cell bodies become oedematous (swollen)

c.      The nucleus becomes eccentrically placed

These changes are more severe if the injury occurs close to the nerve cell body and less severe if they are close to the nerve termination.

3        Recovery of neurons and regeneration of axons occur only if the damage affects the peripheral nerves, and provided their neuronal cell bodies are not damaged. 

a.      Recovery of the cell body begins after about 1 week and is a reversal of the changes of chromatolysis

- The swelling decreases and disappears

- Nissl granules reform (protein synthesis resumes

- The nucleus moves to the centre of the cell

b.     Regeneration of axons in the peripheral nervous system involves a number of steps

- The severed proximal end of the axon sprouts out several fine processes with dilated tips (similar to “growth cones” in developing neurons)

- These filaments continue to grow and elongate if they contact Schwann cells that guide them along their path

- Only one filament contacting a Schwann cell persists in a one-to-one mutual relationship, in which axon growth depends on contact with Schwann cells and is guided by them,  while proliferation of Schwann cells depends on axonal contact

- Myelination of axons begins after the axon contacts an appropriate end organ – muscle in the case of motor nerves

 

The rate of axon regeneration varies from 1 to 4 mm per day. The rate of regeneration is affected by several factors:

- An adequate blood supply

- Alignment of the proximal and distal stumps of the cut axons

- Incorrect alignment may cause axons to grow down a wrong neurilemmal sheath to a nerve ending different from its original ending.  If the nerve ending is inappropriate e.g. motor nerve grows to a sensory ending, or vice-versa, the axon degenerates.  If a motor nerve grows to a different muscle, re-education is possible

- If a gap is present between the stumps, contact of an axon with a Schwann cell would be more difficult, and may not occur

- De-nervated muscles atrophy quite rapidly unless they are maintained by

Faradic stimulation with an electric current and physiotherapy

- Distance of the lesion form the nerve ending makes recovery more difficult and is obviously slower.

If regeneration does not occur, the axons and Schwann cells degenerate and fibrosis (replacement by connective tissue) occurs. 

 

Trans-neuronal Degeneration

This occurs when damage to a neurone also involves degeneration across the synapse the following neuron.  It occurs only in some CNS nerve pathways e.g. damage to the ganglion cells of the retina involves degeneration of the optic nerve and tract, and degeneration of the neurons of the lateral geniculate body to the cerebral cortex. 

 

Several neurological diseases are demyelination disorders Demyelination results in impairment of nerve conduction

Hereditary Motor and Sensory Neuropathy – also known as “Peroneal Muscular Atrophy” is a genetic disorder involving demyelination of nerves of the lower limb, affecting mainly the superficial and deep peroneal nerves.  It results in paralysis of the extensor and peroneal muscles of the leg  with consequent foot drop, and loss of sensation in the feet and legs.

 

Multiple sclerosis is a demyelinating disorder affecting mainly the tracts of the CNS.  It results in progressive generalised muscle paralysis and sensory loss.

 

Peripheral neuropathies may be caused by metabolic disorders.

Diabetic polyneuropathy involves damage to the peripheral nerves.

Vitamin B12 deficiency involves the posterior white matter of the spinal cord.

 

Some neurological disorders involve neuronal degeneration

Spinal Muscular Atrophy is a genetic disorder involving degeneration of the anterior horn cells of the spinal cord. 

 

Tetanus is caused by the toxin released by the bacterium Clostridium tetani, which stimulates the anterior horn cells of the spinal cord resulting in generalised muscle spasm.  It is often fatal.

 

“Why does nerve regeneration not occur in the CNS?”  This is a big problem in neurology.  It appears that there are as yet unidentified factors in Schwann cells that support nerve regeneration, and that are not present in oligodendrocytes.  Solution of this problem might provide some future possibilities for stimulating recovery following spinal injuries.

 

“Stroke” is caused by a cerebrovascular accident.  Occlusion to a small artery supplying the internal capsule results in hemiplegia – paralysis and loss of sensation of one side of the body.  In some cases partial recovery is possible.  This is because the arterial occlusion does not cause death of all neurone;  some neurons are affected by oedema (tissue swelling) that but causes temporary impairment of neurone function, which is recoverable.

 

 

Problems

For each of the following nerve injuries state (a) which neuronal cell bodies would be affected; (b) which nerve or tract would be affected; (c) which function would be impaired; (d) whether regeneration is possible:

 

1        Transection of T1 spinal nerve

2        Injury to the lingual nerve

3        Injury to the facial nucleus

4        Damage to the chorda tympani nerve

5        “Stroke” – vascular occlusion of an artery to the internal capsule

6        Acoustic neuroma, a tumour of the sheath around the auditory nerve