Response of neurons & nerve fibers to injuryTypes of injury Wallerian degeneration, regeneration & Factors for regeneration

RK Goit, Lecturer

Department of Physiology

• Neuron is the basic function unit of the nervous system.

• In the mature human, if it is destroyed, it is not replaced.

• It may be injured due to various reasons(cutting, crushing, pull & pressure).

• These injuries may damage a nerve variously & the injury is classified according to the extent of the damage.

Seddon (1944) described 3 clinical types of nerve injury:

• Neurapraxia (Class I)• the term applied to a transient block

• paralysis is incomplete, recovery is rapid & complete, & there is no nerve degeneration

• pressure is the most common cause

• Axonotmesis (Class II)• the term applied to a nerve lesion in which the axons are

damaged but the surrounding connective tissue sheaths remain intact

• Wallerian degeneration occurs peripherally

• functional recovery is more rapid & more complete than after complete section of the nerve trunk

• crush injuries, traction, & compression are the most common causes

• Neurotmesis (Class III)• the term applied to complete section of the

nerve trunk

• occur on severe contusion, stretch, laceration

Sunderland (1951) expanded Seddon’s classification to 5 degrees:

• First-degree (Class I)• Seddon’s neurapraxia & first-degree are the same

• Second-degree (Class II)• Seddon’s axonotmesis & second-degree are the

same

• Third-degree (Class II)• nerve fiber interruption

• there is a lesion of the endoneurium, but the epineurium & perineurium remain intact

• recovery from a third-degree injury is possible, but surgical intervention may be required

• Fourth-degree (Class II)• only the epineurium remain intact

• surgical repair is required

• Fifth-degree (Class III)• lesion of complete transection of the nerve

• Recovery is not possible without an appropriate surgical treatment

Injury of the Nerve Cell Body• Severe damage of the nerve cell body may

result in degeneration of the entire neuron

• In the CNS, the tissue macrophages (microglial cells) remove the debris, & the neighboring astrocytes replace the neuron with scar tissue

• In the PNS, the tissue macrophages remove the debris, & the local fibroblasts replace the neuron with scar tissue

Injury of the Nerve Cell Process• if the axon of the nerve cell is divided,

degenerative changes will take place in1. distal segment of the axon

2. a portion of the axon proximal to the injury

3. the cell body from which the axon arises

Changes in the Distal Segment of the Axon• wallerian degeneration is the changes that occur

distally to the site of damage on an axon

• axon becomes swollen & irregular; the axon is broken into fragments, & the debris is digested by surrounding Schwann cells & tissue macrophages

• entire axon is destroyed within a week

• myelin sheath is converted into lipid droplets

• the droplets are extruded from the Schwann cell & subsequently are phagocytosed by tissue macrophages

• Schwann cells now begin to proliferate rapidly & axonal sprouts grow from the proximal stump, enter the distal stump, & grow toward the nerve's end-organs

• if regeneration does not occur, the axon & the Schwann cells are replaced by fibrous tissue produced by local fibroblasts

Changes in the Proximal Segment of the Axon• The changes in the proximal segment of the

axon are similar to those that take place in the distal segment but extend only proximally above the lesion as far as the first node of Ranvier

Changes in the nerve cell body • The changes that occur in the cell body

following injury to its axon are referred to as retrograde degeneration

• The Nissl material becomes fine, granular, & dispersed throughout the cytoplasm (chromatolysis)

• the nucleus moves toward the periphery of the cell, & the cell body swells & becomes rounded

• Synaptic terminals are replaced by Schwann cells in the PNS & microglial cells or astrocytes in the CNS

Recovery of Neurons Following Injury• the recovery of the nerve cell body &

regeneration of its processes may take several months

Recovery of the Nerve Cell Body• RNA & protein synthesis is

accelerated

• a reconstitution of the original Nissl structure

• a decrease in the swelling of the cell body

• a return of nucleus to its characteristic central position

Regeneration of Axons in Peripheral Nerves• depend on endoneurial tubes & possessed by

Schwann cells

• The following mechanisms are involved: 1. the axons are attracted by chemotropic factors

secreted by the Schwann cells in the distal stump,

2. growth-stimulating factors exist within the distal stump, &

3. inhibitory factors are present in the perineurium to inhibit the axons from leaving the nerve

Regeneration of Axons in the CNS• Central axons may not be as good at

regeneration as peripheral axons

• The regeneration process is aborted by • failure of oligodendrocytes to serve in the same

manner as Schwann cells,

• laying down of scar tissue by the active astrocytes

• absence of nerve growth factors in the CNS

• neuroglial cells may produce nerve growth-inhibiting factors

References • Clinical Neuroanatomy, 7/E Snell• Essentials of Medical Physiology, 3/E

Mahapatra• Principles of Neural Science, 5/E Kandel ER,

Schwartz JH, Jessell TM (editors)

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