L28 - 30 - Injury to NS Flashcards
Henry Head’s peripheral nerve regen. exp - He cut nerves and general sensation and movement returned except?
Incomplete recovery of light touch, temp, pinpricks, 2-point discrimination, fire motor control
Wallerian Degen
- What is it?
- 2 weeks post injury
- 3 Weeks post injury
- 3 Months post injury
Degen of axon and myelin sheath below injury site
2 weeks: Nucleus becomes peripheral and nissl substance is lost via chromolysis
3 weeks: Schwann cells proliferate, forming a compact cord, growing axons penetrate schwann cell cord
3 Months: successful regen and restoration of elec activity
Neuroma
Occurs during unsuccessful regen where growing axons don’t kinne up with schwann cell cord
GAP43 (Growth Associated Protein 43)
Found in growth cones
Integrins
Binds to ECM to promote growth
In skeletal muscle denervation, NMJ synaptic sites remain intact for weeks - however can also be less accurate
In skeletal muscle denervation, NMJ synaptic sites remain intact for weeks - however can also be less accurate
Is crush or cut injury good for regrowth?
Crush = good regrowth Cut = variable
Microsurgery
Reattach proximal and distal stumps or insert nerve graft
Regeneration of peripheral nerves is faster with exercise
Regeneration of peripheral nerves is faster with exercise
Tau deposition is found in
Alzhemiers diseased brains
3 major classes of glia in CNS that react to tissue damage
Astrocyte, oligodendrocytes, microglia
Astrocytic Gliosiis
- Upregulate astrocyte cytoskeletal proteins e.g. GFAP (Glial fibrillary acidic protein)
- Upregulate expression of developmental axon guidance molecules
- Hypertrophic
- Proliferate
- Secretes cytokines and GF
- Interdigitate processes
- Secrete ECM e.g. CSPG (chondroitin sulphite proteoglycans)
How can upregulating axon guidance molecules via astrocytic gliosis be bad?
In development, they are expressed in certain channels by repulsing axons that touch it so they get bumped into the right direction. In adults, there is no path for them to follow, so when an axon hits it, it just stops or retracts. This leads to Glial Scar formation
Glial Scar Formation
Forms a barrier between undamaged tissue and injuy site
Nogo, MAG - what are they and what do they bind to
Inhibitory molecules in myelin debris
Binds to Nogo receptor (NgR)
Signalling of Nogo receptor activation is done via? It associates with?
Rho A activation -> ROCK -> cytoskeleton -> neurite inhibitions
Associates with p75/LINGO or TROY/LINGO
Eph/ephrins, semaphorins, tenascin- what are they?
Axon guidance molecules
GFAP (Glial fibrillary acidic protein)
Astrocyte cytoskeletal protein
CSPG (chondroitin sulphite proteoglycans) and Collagen IV
Astroctye ECM
TGFB (transforming growth factor B) activates astrocytes, what happens when you block it?
Nothing - it doesn’t aid in regeneration
Increase/decrease regen:
- Astrocyte ECM inhibition
- GFAP.Vimatin double KO
- Astrocyte ablation
- Blocking Eph A4 (activates Rho)
All increases
Nogo and Rho inhibition - amount of regen?
Some
Location of neurogenic regions that make stem cells
SVZ and SGZ
1) Subventricular zone of lateral ventricle (goes to olfactory bulb via rostral migratatory stream)
2) Subgranular zone of dentate gyrus of hippocampus (goes to GL layer of hippocamppus)
EPO
Increases neurogenesis in brain
Inflammatory soup
cytokines, chemokines, metalloproteases
*Chemokines attract stem cells from injury site, affecting recovery
