Neural Regeneration

Question 1

true/false neither CNS or PNS neurons can regenerate

Answer 1

False, when peripheral axons are damaged, the proximal portions can partially or completely regenerate distally. (cell body can be in PNS or CNS).

Question 2

what process tends to inhibit regeneration of central axons/neurons

Answer 2

glial scar formation

Question 3

what can be expected up to 2 weeks post PNS axonal injury?

Answer 3

peripheral nucleus
loss of nissl substance (chromolysis)

wallerian degeneration

• degen of axon and myelination sheath below the site of injury
• ->debris phagocytosed by macrophage influx

–>Muscle Fibre Atrophy

Question 4

What happens 3wks post PNS axonal injury

Answer 4

schwann cell proliferation, creating compact cord.

growing axon penetrates the compact cord.

–>muscle fibre atrophy continues

Question 5

What can happen 3 months post PNS axonal injury? (successful cases)

Answer 5

successful regeneration
-electrical activity restored

—>muscle fibre regeneration!

Question 6

What can happen 3 months post PNS axonal injury? (unsuccessful cases)

Answer 6

neuroma formation, bundling of axon at the site of injury

–>muscle fibre atrophied

Question 7

T/F crushed and cut axons regenerate at the same rate

Answer 7

FALSE. repair is faster if axon is crushed rather than cut.

• the better preserved the axonal alignment the easier is to regenerate.
• in cut axons some may regenerate incorrectly, end up servicing the wrong conduits.

Question 8

details of primary CNS spinal cord injury (incl Tx)

Answer 8

immediate.
injury due to physical damage –>cellular loss

Tx to minimize extent of primary damage. (ex tissue plasminogen activator for stroke)

Question 9

details of secondary CNS spinal cord injury in short term (minutes/hours)

Answer 9

degenerative insults.

• ischaemia
• Ca 2+ influx
• lipid peroxidation & free radical production
• glutamate excitotoxicity
• BBB breakdown

Question 10

details of secondary CNS spinal cord injury over hours to days/weeks

Answer 10

• immune cell infiltration, microglial activation

- cytokines, chemokines, metalloproteases

Question 11

details of secondary CNS spinal cord injury over days/weeks

Answer 11

• axonal degeneration
• demyelination
• apoptosis - neuronal and oligendendroglial
• astrocytic gliosis and glial scar formation
• syrinx cavity formation and meningeal fibroblast migration

Question 12

strategies to repair the CNS?

Answer 12

• protect surviving cells
• regrowth of surviving neurons & remyelination
• modulate astrocytic gliosis (wound repair and scar formation)
• neural stem cells (mobilise endogenous cells, transplant exogenous cells)

Question 13

what factors impede axonal regeneration and how to tx?

Answer 13

Problem: lack of trophic support
Solution: encourage axons to grow by providing growth promoting factors (neurotrophin: NGF, BDNF)

Prob: axon regrowth inhibited by wound environment
Soln: inhibit growth blocking factors. Ie astrocytic gliosis and glial scar; myelin inhibitors; developmental guidance molecules

Question 14

Axonal plasticity vs axonal regeneration?

Answer 14

Plasticity described compensation by other uninjured axons to branch and service the conduits previously innervated by the injured axon.–>”axonal sprouting”

regeneration is complete renewal of injured axon

Question 15

what does astrocytic gliosis cause?

Answer 15

• upregulate astrocyte cytoskeleton proteins (GFAP).
• secrete ECM (chondroiton sulfate proteoglycans)
• secrete cytokines (IL-1, TNF-alpha) and growth factors (NGF/BDNF)
• increase expression of development axon guidance molecules

–>glial scar formation–>forms a barrier between injury site and healthy site

Question 16

how to inhibit astrocyte gliosis and improve regeneration?

Answer 16

blocking of astrocyte ECM via CSPG inhibition or collagen IV inihibition