ervous system: central nervous system (CNS) and eripheral nervous system (PNS) NS includes the brain and spinal cord NS consists of the cranial

Transcription

1 Physiology of the peripheral nervous system ervous system: central nervous system (CNS) and eripheral nervous system (PNS) NS includes the brain and spinal cord NS consists of the cranial nerves from brain and pinal cord ensory (afferent) nerves direct impulses from ensory receptors to the CNS otor (efferent) nerves conduct impulses out of the 1

2 Cellular components of the peripheral nervous system wo cell types: neurons and neuroglia eurons basical element with a cell body containing e nucleus, a long cell process (axon) and several hort cell processes (dendrites) endrites xon electrical signals to the body impulses away from the cell body euroglia (or glial cells): non-neural support of cells nd aid the function of neurons 2

3 Axon in the PNS surrounded by a living sheath of Schwann cells Difference PNS and CNS peripheral nerves to regenerate capacity for Axons consist of a myelin sheath (fat-containing cells that insulate the axon from electrical activity): increase of propagation of velocity of the nerve impulse 3

4 Anatomy of a nerve erve as a bundle of motor/or sensor axons linked gether by support tissue ndoneurium broblasts erineurium ollagen pineurium ssue oriented collagen fibers and multiple layers of flattened cells and outer sheath of loose fibrocollagenous 4

5 Peripheral nerve response to injury (1) he most severe injury is a complete nerve transection evered axon distal portion begins to degenerate and t the proximal end the nerve stumps degeneration ccurs allerian degeneration (secondary degeneration) one to o hours after injury and over four days after transection 5

6 Peripheral nerve response to injury (2) Axons and myelin beyond the site of injury phagocytosed by proliferating Schwann cells and macrophages Target muscle chromatolysis atrophy and neuron cell body Schwann cells proliferate and migrate formation of cellular bridges and processes axon regeneration 6

7 Peripheral nerve response to injury (3) ynthetic nerve guidance channels (NCGs) to study the nderlying mechanism of peripheral nerve regeneration uide channels aps end-to-end repair and repair long nerve uidance channel: reduce tension at suture line protects the regenerating nerve from infiltrating scar tissue directs the sprout axons towards distal target 7

8 Axonal regeneration At the proximal end of the damaged nerve the axon regenerate by sprouting new processes: elongation Schwann cell guide (2-5mm/day) Integral nerve synapse as a functional connection between a neuron (pre-synaptic cell) and a second cell (post-synaptic cell) actional potential stops at the pre-synaptic axon ending the axon must re- For a damage nerve to regenerate establish a functional synapse 8

9 Use of nerve guidance channels: Properties Permeability (diffusion of macromolecules) Electrical properties (uncharged tubes) Must be simple to implant surgically Not made of permanent and rigid materials (to be degradeted or resorbed) 9

10 Conduit material: Natural materials Laminin, fibronectin and collagen promote axonal extension materials for NGCs (Nerve Guidance Channels) Natural materials: biocompatibility good surface for cell adhesion induction of undesiderable immune response use of natural proteins limited by poor mechanical properties synthetic materials for NGCs 10

11 Conduit material: synthetic materials Polyesters, degradable polyurethanes, polyphosphazenes support nerve regeneration 11

12 12 Schematic illustration of a nerve guidance channel and some of the possibile strategies for influencing nerve regeneration

13 resent data suggest that ideal NGC: hould be biocompatible, biodegradable, non-immunogenic, turable and pliable hould have a smooth inner linner of the conduit wall hould have ineherent electrical properties hould have a highly porosity to support cell attachment and igration hould release soluble neutrophic factors either by direct corporation of the molecules or by inclusion of support cells.g. Schwann cells) 13

14 Example tube ore space n Fibres Fn tube filled with Fn fibre Hyaluronan layers placed either lining the inner wall or outside Fn tube or both Inner core space between Fn guidance fibres may be filled with an Ha hydrogel HA sheath 14

15 Fn implants have been found to be strikingly effective in encouraging strong axon regeneration To be tested incorporation of anti-tgf-bl, HA, fibrinogen, copper, growth factors into the FN materials 15