20.3 Flashcards
(20 cards)
In the CNS (brain and spinal cord) there is ___ regeneration, and in the PNS (cranial and peripheral nerves) there is ___ regeneration.
Minimum/No
Some
When peripheral axons/nerves are damaged, the ___ part of the axon can regenerate ___.
Proximal part can regenerate distally.
When peripheral nerves are damaged, repair occurs and the cell body can be in a peripheral ___ OR in the ___
Peripheral ganglion OR in the CNS - if damage is to the peripheral nerve than repair can occur.
When central axons or neurons are damaged:
Some neurons die.
Some neurons retract processes, but can sprout to form new local connections.
GLIAL SCAR/GLIOSIS - that inhibits regrowth!
In a normal neuron/nerve fibre, the nucleus is ___ located, and there is a ___ ___ substance (ribosomes) with intact innervated muscle fibre.
Centrally located in cell body
Dense Nissl substance due to high level of ribosomes
Up to 2 weeks after nerve injury, the nucleus is ___ located, and there is loss of ___ ___ (process called ___), and there is ___ degeneration - degeneration of axon and myelin sheath under the site of injury due to macrophages removing debris.
There is also muscle fibre atrophy.
Peripherally located in cell body.
Loss of Nissl substance (chromolysis).
Wallerian degeneration.
3 weeks post-injury, ___ cells proliferate to form a compact cord, and growing axons penetrate this cord.
Schwann
Up to 3 months post-injury, there can be successful regeneration, electrical activity and ___ fibre regeneration, OR there can be unsuccessful regeneration with ___ formation that can be painful.
Muscle
Neuroma
Repair is faster if an axon is ___ rather than ___. Why?
Crushed rather than cut!
Because in crush injury the ECM is intact (acts as a guide for growth).
___ cells and the ___ matrix in distal parts acts as a guide for ___ cones.
Schwann cells and ECM
Growth cones
This explains why crushed nerves repair faster than cut nerves.
Oligodendrocytes ___ growth, whereas Schwann cells ___ growth.
Inhibit
Promote
Major difference for ability of CNS to repair c.f. PNS.
Describe the process of CNS nerve injury:
Physical damage due to primary injury -> cell loss.
Secondary injury - minutes to hours, degeneration due to ischaemia, excitotoxicity, Ca2+ influx, etc.
Secondary injury - hours to days/weeks, immune cell infiltration and microglial activation.
Secondary injury - days/weeks, axonal degeneration, demyelination, apoptosis (of neurons and oligodendrocytes), astrocytic gliosis and syrinx/cavity formation, meningeal fibroblast migration.
Name 3 ways to promote repair of the CNS:
Axonal regeneration and functional integration - remyelination?
Modulate astrocytic gliosis - because this inhibits axonal regeneration!
Neural stem cells.
In the CNS, why is axon regrowth inhibited?
May be due to no trophic support - try using growth factors e.g. neurotrophins.
May be due to environment i.e. astrocytic gliosis and myelin inhibitors.
Note that regeneration refers to a nerve that ___ and reconnects, but sprouting or plasticity is NOT considered regeneration.
Regrows
By blocking astrocyte ECM (CSPG inhibition, collagen IV inhibition) you can ___ regeneration.
Increase
There are ___ inhibitors on ___ debris that inhibit regeneration
Myelin inhibitors on myelin debris
Myelin proteins bind to the ___ receptor (NgR) and activates the ___ signalling pathway that ___ axon growth.
Nogo
Rho
Inhibits axon growth
When a growing axon interacts with ___, it activates ___ and growth stops!
Interacts with Rho and activates it!
So maybe if we block Rho we can promote axon regrowth.
The two main neurogenic (i.e. neural stem cell areas) areas in the adult mammalian brain are:
The subventricular zone of lateral ventricle.
The subgranular zone of dentate gyrus in hippocampus
