Injury and potential for recovery in CNS

Question 1

CNS vs PNS

Answer 1

CNS = spinal cord and brain
PNS = cranial nerves, ganglia and spinal nerves

Question 2

Give 5 types of injury in CNS

Answer 2

• developmental
• trauma
• ischaemic (stroke)
• hypoxic (cardiac arrest)
• inflammatory (MS)
• Neurodegenrative (AD,PD)
• infection (meningitis, encephalitis)
• tumours

Question 3

Pathology

Answer 3

• most types of injury affect neurons, glial cells, BBB, CSF

Question 4

What is stroke?

Answer 4

• blood supply to part of brain occluded
• acute loss of blood supply damages regions supplied by blocked artery
• takes 6-8 mins of ischaemia to cause infarction

Question 5

Hypoxic brain injury

Answer 5

• reduction of whole brain oxygenation
• preferentially affects the most metaboloically active parts of the brain - grey matter of cerebral cortex and basal ganglia

Question 6

Multiple sclerosis

Answer 6

• inflammation > demyelination > neuronal dysfunction
• autoimmune condition that attacks myeline sheath leading to neuronal dysfunction
• MR gives patchy high signal areas where you’d expect white matter

Question 7

How does injury affect neurons and their connections?

Answer 7

• fate of neuron following axotomy and target loss - axon is cut (cant transmit signals), loss of trophic factors and support
• neurons that lose their normal input are denervated
• damage has 2 consequences: upstream, the cell body may die via apoptosis (retrograde degeneration). downstream, distal axon dies (anterograde degeneration)

Question 8

Regeneration in CNS vs PNS

Answer 8

• PNS can regrow if nerve sheath remains intact. Helped by clean up of damaged parts by macrophages, Schwann cells, and the speed of clean-up
• most CNS fibres wont regenerate - clean up is slow, oligodendrocytes inhibit regeneration, and environment isnt optimal

Question 9

What is Sunderland’s classification of nerve injury?

Answer 9

• Grade 1 - neuropraxia (conduction disruption with intact axon and supporting structures. full recovery within days, no surgery needed)
• Grade 2 = Axonotmesis (disrupted axon, intact endoneurium, variable recovery)
• Grade 3 = Neurotmesis with preservation of perineurium (endoneurium is disrupted, 60-80% recovery)
• Grade 4 = Neurotmesis with pres. of epineurium (requires nerve grafting)
• grade 5 = neurotmesis with complete transection of nerve trunk (need bypass/jump grafting)

Question 10

Glial scarring

Answer 10

• gliosis involves proliferation of astrocytes and microglia after CNS injury to protect and aid in healing process
• has beneficial and detrimental effects
• regenerates a tissue barrier after BBB compromise and promotes revascularisation of injured brain
• neuro-developmental inhibitors are secreted by astrocytes that prevent axon regrowth and regeneration

Question 11

Neurogenesis

Answer 11

• birth of new neurons

- only evidence for it occurring in hippocampus and near the lateral ventricles

Question 12

How do you fix the brain if you cannot regrow new neurons?

Answer 12

• compensation - brain areas take over functions of damaged area
• new terminals from presynaptic neurons - additional synapses and more receptors
• reorganisation

Question 13

How do we know neuroplasticity exists?

Answer 13

• fMRIs show changes in brain activity pre and post stroke

- brain connections change with unaffected side compensating

Question 14

Treatments

Answer 14

• constraint-induced movement therapy (make stroke patients do things with their bad arm by impeding their good one)
• transcranial magnetic stimulation (magnetic fields cause stimulation of cells to release NTs)
• Stem cells
• Induced pluripotent stem cells
• brain-machine interfaces