Neural Regeneration Flashcards
Which nerves have better regeneration - ones in the PNS or ones in the CNS?
the PNS
What happens to a peripheral nerve for the 2 weeks after nerve injury?
nucleus become peripheral, chromolysis, wallerian degeneration and muscle fibre atrophy
What is wallerian degeneration?
degeneration of axon and myelin sheath below the site of injury - debris is phagocytosed by macrophages
What happens to a peripheral nerve 3 weeks after nerve injury?
regeneration starts - the nucleus become more central, there are more nissl bodies, schwann cells proliferate and fill the nerve fibre and the growing axon penetrates the schwann cells
How long does it take for the peripheral nerve to fully regenerate and restore electrical activity?
up to 3 months
What is a neuroma?
a neuroma is the product of unsuccessful regeneration - a bundle of nerve fibres that can be painful
Why is repair faster if a nerve is crushed rather than cut?
because the alignment of the nerve is a key factor - the better the alignment the better the outcome
What is primary damage in the CNS?
the immediate physical damage and cell loss in a small site
What is secondary damage in the CNS?
the degenerative insult around the area of primary damage due to ischaemia, calcium influx, lipid peroxidation and free radical production, glutamate excitotoxicity and blood brain barrier breakdown - followed by immune cell infiltration and activation - all of this will result in axon degeneration and demyelination
What are the two factors which stop axonal regeneration in the CNS?
a lack of trophic support and inhibition by the injury environment
What factors in the injury environment inhibit axonal regeneration in the CNS?
astrocytic gliosis and myelin (oligodendrocytes)
What treatment has been trialed to counteract the lack of trophic support and why was it unsuccessful?
giving neurotrophins such as NGF and BDNF but has adverse effects such as neuropathic pain
Why is astrocytic gliosis inhibitory to axonal regeneration?
because it provide a physical barrier to growth, it secretes an extracellular matrix that is inhibitory to growth and produces cytokines that are inhibitory to growth
What treatment has been trialed to counteract the astrocytic gliosis?
blocking the molecule that activates astrocytes (TGFbeta) - didn’t work because it was activated by other molecules, blocking the activity of the extracellular matrix secreted by the astrocytes - had some efficacy, blocking the GFAP cytoskeleton molecule in astrocytes - had some efficacy, completely blocking astrocytes - detrimental
What proteins produced by oligodendrocytes are inhibitory to axonal regeneration?
Nogo, MAG and OMgp
What receptor do the inhibitory proteins produced by oligodendrocytes bind to and what pathway does this activate?
they all bind to the Nogo receptor which activates the rho A kinase pathway
What treatments have been trialed to counteract the inhibitory proteins produced by oligodendrocytes?
Nogo blockers, rho inhibitors, anti-nogo antibodies
What are axon guidance molecules?
molecules that promote, repel or guide growing axons in development that may be upregulated or re-expressed in the adult after injury e.g. EphA4
Why is rho kinase potentially a good target for neural regeneration?
because it is a common pathway to target lots of inhibitory effects such as myelin inhibitors, axon guidance molecules, astrocyte activation
What are the two potential ways to use stem cells to repair nervous system injuries?
transplant stem cells or activate cells already present
What are the two main neurogenic regions in the adult mammalian brain?
the sub ventricular zone of the lateral ventricle and the sub granular zone of the dentate gyrus in the hippocampus
