Nerve damage

Question 1

What are the challenges of nerve repair

Answer 1

Nerve injury may spread- to the cell body (spinal cord, ganglia)
- through transneuronal degeneration

Nerve repair may happen but is not always successful

Question 2

What does the success of nerve repair depend on?

Answer 2

Severity of initial injury (what has been damaged and how much if it)

The extend of secondary damage

Question 3

What is the meaning of Neurapraxia, Axonotmesis

and Neurotmesis? What is effected in each condition?

Answer 3

Neurapraxia: temporary loss of motor and sensory function due to blockage of nerve conduction
(myelin effected, reversible)
Axonotmesis: a disruption of axons, resulting from severe crush
(myelin,axon,epineurium, wallerian degeneration, reversible)
Neurotmesis: both the axons and the nerve sheath are disrupted
(myelin, axon, epineurium, wallerian degeneration, irreverisble)

Question 4

What happens after a nerve has been damaged?

Answer 4

The ion channels and proteins involved in neurotransmision decreases.

NEURONS SWITCH FROM A TRANSMISSION STATE TO A GROWTH STATE

proteins involved in axonal growth increases

Neurotrophic factors
released by innervated cells
taken up by the nerve terminals
transported retrogradely to the neuronal cell body to promote neuronal growth and survival

Question 5

Give 2 examples of neurotrophic growth factors

Answer 5

NGF: Nerve Growth Factor
BDNF: Brain-Derived Neurotrophic Factor
GDNF: Glial cell-Derived Neurotrophic Factor

Question 6

What is the process of nerve regeneration?

Answer 6

Schwann cells divide, secrete trophic factors to attract axon, then remyelinate new axon

Question 7

Why does time matter in nerve repair?

Answer 7

1. Prolonged axotomy significantly reduces the number of motoneurons and their axons that can regenerate
2. After 1 month, Schwann cells down-regulate
   regeneration-associated factors

3.Prolonged muscle denervation :
Muscle atrophy and fibrosis
Profound decrease in numbers of regenerating axons through the deteriorating intra-muscular sheath

Question 8

How are spinal cord injuries repaired?

Answer 8

Spinal cord trauma produces a site of primary cell death (the “epicentre”), which rapidly spreads into a zone of secondary cell death

Macrophages and microglia engulf debris and the injury site becomes walled off by a glial scar

At the glial scar, axons show an abortive sprouting response; distal tracts undergo Wallerian degeneration

Question 9

What is the function of glial scars in spinal cord injury?

Answer 9

ENGULFS DEBRIS

SEALS THE LESION SITE

REPAIRS THE BBB

EXPRESSES CHEMICALS THAT INHIBIT AXON GROWTH (CHONDROITIN SULPHATE PROTEOGLYCANS –CSPGs)

Question 10

What are the two main barriers to CNS repair?

Answer 10

Hostile Environment
Scar tissue (physical; chemical barrier –CSPGs)
Myelin-associated inhibitory proteins:
Nogo proteins;
MAG (Myelin-Associated Glycoprotein);Omgp (Oligodendrocyte myelin glycoprotein)

Poor regenerative response

Question 11

List mechanisms to increase nervous system repair

Answer 11

Neuro-protection- to contain the effects of early trauma, inflammation, and scar formation (Omega-3 polyunsaturated fatty acids)

promotion of axonal regeneration- positive trophic support- growth factors, Cell / tissue transplantation

counteracting inhibitory influences
Enzymes to target inhibitory prot

Guiding axonal regrowth
to re-establish appropriate connectivities- Biomaterial scaffolds

Activity-based rehabilitation