nerve injury, CNS vs PNS Flashcards
what suggested that the environment in the CNS influences the neuron capabilities to regenerate?
- peripheral neurons capable of regeneration in the PNS lose their ability to do so in a CNS nerve graft a
- the ability of CNS euros to regenerate is improved in a PNS nerve graft
what are 4 main roles of the astrocyte normally?
hey produce trophic support for neurons, perform homeostatic maintenance of the extracellular ionic environment and pH, clear and poten- tially release glutamate, provide metabolic substrates for neu- rons, couple cerebral blood flow to neuronal activity, and play a key role in synapse formation, maintenance, and function
what is the name of the process that astrocytes undergo following injury?
reactive gliosis
what is the role of oligodendrocytes?
- they ensheath the neurons of the CNS they can ensheath up to 50 neurons
what percentage oligodendrocyte deaths observed in oligodendrocytes following injury and how does this compare to SCs in the PNS?
- 30-40% next to near complete survival of SCs normally
what can cause oligodendrocyte death after injury?
- release of cytokines from the glia, sensitivity to oxidative stress, infiltrating neutrophils
of those oligodendrocytes that do make it through injury and dont die, what is their phenotype?
- no repair response, essentially quiescent and do not contribute to the demyelination of spared axons
ow can activating the PI3K pathway have dual advantages?
- promotes both survival and skeletal cytoskeleton rearrangements for neural outgrowth
how is the presence of neurotrophic factors important in terms of regeneration vs apoptosis?
- it is thought that a dual leucine zipper primes the injured neuron for two possible responses: regeneration or apoptosis and the path that is taken is determined by the abundance of pro or anti regenerative cues
why is PNS injury so full of growth promoting factors~?
the schwann cells release them
when you delete c-jun, what happens and what is this thought to cause?
increased neuronal cell death, it is thought that c-jun mediates the release of growth factors
are astrocytes able to support neuronal survival in vivo like SCs?
Although trophic factors are produced by astrocytes after injury and astrocytes are sufficient to keep CNS neurons alive in culture, these factors are not present in the combinations and spatial and temporal gradients needed to support neuron survival in vivo
what is the difference in basal lamina levels in the CNS and PNS and how does this relate to regeneration?
One of the major differences between the CNS and PNS is the abundance of basal lamina. Schwann cells secrete a basal lam- ina composed of growth-promoting laminin, type IV collagen, and heparin sulfate proteoglycans (HSPGs), which is crucial to the ability of these cells to myelinate (Bunge et al., 1990). Inter- estingly, oligodendrocytes secrete no basal lamina, and, with the exception of the pial surface and places where astrocytes contact blood vessels, the healthy CNS is largely devoid of these molecules. The abundance of basal lamina surrounding Schwann cell-ensheathed axons in the mature PNS and upregulation of proregenerative extracellular matrix (ECM) molecules by Schwann cells after injury plays a key role in PNS regeneration - these are released by bands of bungner
ow is the importance of laminin in regeneration shown?
Consistent with an important role for laminins in PNS regeneration, motor neurons upregulate integrins (laminin receptors) on both their cell bodies and axons in response to injury, and mice lacking these integrins exhibit reduced axon outgrowth
how does laminin binding to integrin promote outgrowth?
Although this mechanism is still being defined, the integrin-laminin interac- tion is known to trigger PI3-kinase activation, Akt signaling, and cytoskeletal rearrangements favoring axon growth, suggesting that trophic factors and growth-promoting ECM molecules may converge on common intracellular signaling pathways to induce axon outgrowth
