Flashcards in Neural Regeneration Deck (18):
What are the histological features of a normal neuron?
biggest cells, can look triangular, central nucleus, dense nissl substance, prominent nucleolus, granular cytoplasm
What are the signs (histological) of a injured neuron (2 weeks post-injury)?
peripheral nucleus, loss of Nissl substance (chromolysis, chromatolysis), Wallerian Degeneration (of axon and myelin sheath)
Describe the steps in the response to injury in the PNS
damage to cell body (peripheral nucleus and chromolysis - loss of nissl substance), Wallerian degeneration of the axon and myelin sheath and phagocytosis of debris by macrophages. Schwann cells proliferate and form a compact cord, as the peripheral axon (proximal to injury site) starts to extend in penetrates the schwann cell region. Approx 3 months post injury if all has gone well the axon has regenerated and reconnected with its target muscle
What is a neuroma and how does it form?
growth of neural tissue - sign of unsuccessful regeneration -> forms in response to growth factors in the environment but axon fails to reconnect and get to right target
Is repair faster in peripheral nerves if the axon is crushed or cut? why?
crushed - continuous schwann cell and ECM framework to guide and properly align proliferating axon
Why doesn't injury to the CNS regenerate like the PNS?
CNS structure is much more complex -> not single neuron & axon, Oligodendrocytes = inhibitory, slow phagocytosis of axonal and myelin debris (strong growth inhibitory signal), nerve structure is often destroyed, Astrocyte gliosis inhibits regeneration
What is the difference between sprouting and regeneration?
Sprouting is the growth of an uninjured neuronal axon to reach and takeover supply of the target of a damaged neuron -> no growing of injured neuron occurs. Regeneration involves the growth of the damaged axon past the site of injury.
What occurs in astrocyte gliosis?
Upregulation of astrocyte cytoskeletal proteins (GFAP), hypertrophy and proliferation of astrocytes, interdigitation of processes, secretion of cytokines and GFs, secretion of ECM, upregulation of expression of development axon guidance molecules. Process only occurs in CNS - no astrocytes in PNS
How can we target astrocyte gliosis to aid in regeneration?
blocking the production of ECM helps remove some of the inhibitory environment, but blocking activation of astrocytes altogether gives worse outcomes.
What are the outcomes/goals of astrocyte gliosis?
Scar (physical, molecular) that acts as a barrier between undamaged tissue and injury site. Also involved in BBB repair
What factors inhibit the growth of axons?
myelin debris (Nogo, MAG, OMgp), axonal guidance molecules (semaphorins, eph) on activated astrocytes <- upregulated after injury
How do proteins on myelin debris inhibit axonal regeneration?
myelin proteins (Nogo, MAG, OMgp) bind to the Nogo receptor (HgR) and result in Rho signalling which inhibits axon growth
How can inhibiting Rho Kinase influence axonal regeneration?
Rho pathway important in inhibiting axonal growth, Rho kinase also important in activating astocytes
Where are the two main stem cell niches in the brain?
Subventricular zone of the lateral ventricle
Subgranular zone of the dentate gyrus in the hippocampus
How do stem cells from the SVZ vs SGZ vary?
SGZ stem cells respond to injury but only alter neurogenesis in the hippocampus but SVZ migrate to site of injury
How does secondary neural injury develop?
starts off as a primary injury with loss of neuronal cells, within minutes to hours degeneration begins = secondary injury due to ischaemia, calcium influx, lipid peroxidation and free radical production, glutamate excitoxicity, BBB breakdown following this there is immune cell infiltration and microglial activation and the release of cytokines, chemokines, metalloproteinases --> axonal degeneration, demyelination and apoptosis(neuronal and oligodendrocyte) followed by the formation of a glial scar
what are some strategies to treat secondary neuronal injuries?
methylpredisolone (not in aus) EPO