Neuro 1 Degeneration (PDF)

RE/DEGENERATION IN THE NERVOUS SYSTEM The effects of neuronal injury AXOTOMY (axontmesis) • Most injuries to the nervous system affect the axon • Physical trauma, vascular insufficiency, metabolic disorders, tumours etc can affect nerves in the CNS or the PNS • Injury to the axon divides the neuro...

RE/DEGENERATION IN THE NERVOUS SYSTEM The effects of neuronal injury AXOTOMY (axontmesis) • Most injuries to the nervous system affect the axon • Physical trauma, vascular insufficiency, metabolic disorders, tumours etc can affect nerves in the CNS or the PNS • Injury to the axon divides the neuron into a proximal portion that retains its attachment to the cell body, and a distal fragment Chromatolytic Reaction • The proximal part of the axon and the cell body are likely to die by apoptosis; if not, the cell body undergoes chromatolytic reaction (axon reaction) • • • • eccentric nucleus Nissl substance fragmentation increase of RNA and protein synthesis changes in the expression of the neuron’s genes Wallerian Degeneration • The distal segment of the injured axon undergoes Wallerian degeneration • axonal degeneration • myelin sheath fragmentation • axonal and myelin debris is enveloped and destroyed by microglia Transneuronal Anterograde Degeneration • The postsynaptic neuron is affect because of lack of input, and eventually atrophies and dies depending on the extend of the neuronal damage Transneuronal Retrograde Degeneration (synaptic stripping) • The neuron that provides the injured cell with input also undergoes changes • synaptic space increases and is interrupted by glial processes: • The glia cells involved are Schwann cells in the peripheral nervous system and Astrocytes or microglia cells in the central nervous system Regeneration • Peripheral neurons have a higher capacity to regenerate after injury than central neurons • Connective tissue elements survive in the distal fragment of the axotomized neuron • The proximal fragment grows axonal sprouts that are guided to the distal portion by chemotropic factors secreted by Schwann cells • Axonal growth is promoted and the regenerated axons find their targets • *****Axons may be guided to inappropriate targets (i.e. Frey’s syndrome) or never reach their destination • If the axonal sprouts do not make contact with the distal element, they become entangled and form a benign mass known as a neuroma. Factors contributing to the decreased capacity of the CNS neurons to regenerate 1. Schwann cells • Schwann cells are the myelin producers of the PNS • They produce growth promoting factors that render the peripheral nerve’s environment more conducive to regeneration • In the embryo both central and peripheral nerves promote axonal growth; only the PNS retains that ability 2. Inhibiting factors • Both the PNS and the CNS can secrete growth promoting factors after injury but the CNS also contains inhibiting factors • Central myelin is a potent axonal growth inhibitor • In the CNS myelinization occurs after axonal growth is complete 3. Intrinsic differences • The central nervous system cells express proteins that render them less able to regenerate after the initial formatting stages 4. Scarring and Inflammation • With a central injury we see • • • • scar formation astrocyte proliferation microglia and other immune cell recruitment inflammation • If the surrounding tissues are selectively excluded, healing is enhanced Clinical Considerations • Introduction of trophic substances • Schwann cell grafts • Introduction of antibodies against axonal growth inhibitors • Transplantation of fetal tissue • Administration of immunosuppressants, antiinflammatory steroidal agents