Injury and potential for recovery in the CNS

Question 1

What are the different types of injury in the CNS?

Answer 1

• Developmental
• Traumatic (brain or spine)
• Ischaemic (stroke)
• Hypoxic (cardiac arrest)
• Inflammatory (MS)
• Neurodegenerative (Alz, park’s)
• Infection (meningitis)
• Tumours

Question 2

How can you tell what oedema looks like on a CT scan?

Answer 2

The dark grey areas are shown as oedema, in picture it is prominent as there is distorted anatomy, mass effect where right side pushing over the left as midline has shifted.

Question 3

Why is stroke damaging?

Answer 3

As there is an acute loss of blood supply to part of the brain (supplied by the blocked artery)

Question 4

How long does it take of blood supply interruption to cause neuronal death in a stroke?

Answer 4

6-8 minutes of ischaemia

Question 5

Most cerebral vascular occlusions will reopen spontaneously within 24 hours. Why is this not enough?

Answer 5

As it is too late for the neurons, in 24 hours you lose 2 million neurons per minute.

Question 6

What is hypoxic brain injury and where does it impact the most?

Answer 6

Reduciton of whole brain oxygenation, affects most metabolically active parts so GREY MATTER (cerebral cortex, basal ganglia).

Question 7

What is multiple sclerosis?

Answer 7

Auto-immune disease where inflammation causes demyelination -> neuronal dysfunction.

Question 8

What (briefly) happens to the brain size in Alzheimer’s?

Answer 8

Shrinking of total brain substance, gryi and sulci much more prominent.

Question 9

How does injury affect neurones and their connections?

Answer 9

Loss of trophic factors and support and causes denervation

Question 10

What are the two major consequences for a neuron following the death of its axon?

Answer 10

1. Upstream, cell body may die via apoptosis (retrogade degen)
2. Downstream, distal axon dies, via Wallerian degen (anterogade degen)

Question 11

What are consequences of denervation for the target neuron?

Answer 11

• Subtle changes eg. NT hypersensitivites -> muscle spasticitiy
• Transneuronal atrophy/degen eg. visual/auditory systems

Question 12

Can our nervous system regenerate?

Answer 12

PNS vs CNS

• PNS axons can regrow if their myelin remains intact, clean up of damaged parts is done by macrophages and then schwann cells assist in regeneration. Time is important, faster cleanup helps regen.
• Most CNS fibres do not regenerate, clean up is slow and oligodendrocytes inhibit regeneration. Environment not optimal.

Question 13

Describe Sunderland’s classification of nerve injury (details/technical stages not required)

Answer 13

Graded I - V

1. Neuropraxia - conduction disruption with intact axon and preserved myelin, normal full recovery in weeks.
2. Axonotmesis - disrupted axon with intact endoneurium; Wallerian degeneration after 1-2 weeks, variable recovery
3. Neurotmesis w/ preservation of perineurium - disruption of endoneurium, 60-80% recovery
4. Neurotmesis w/ preservation of epinurium - required nerve grafting
5. Neurotmesis w/ complete transection of nerve trunk - bypass/transplant/jump grafting

Question 14

Glial scar formation is a reactive cellular process involving proliferation of astrocytes and microglia after injury to CNS. How is this both beneficial and detrimental?

Answer 14

1. Beneficial - regenerates tissue barrier after blood-brain barrier compromise and promotes revascularisation of injured brain
2. Detrimental - neuro-developmental inhibitors are secreted by astrocytes that prevent axon regrowth and regen.

Question 15

What is neurogenesis?

Answer 15

• Birth of new neurones, the adult mammalian brain produces relatively few neurons, but there is evidence for it.

Question 16

What are the two areas of the brain that support evidence for neurogenesis?

Answer 16

1. Hippocampus
2. Subventricular zone (near lateral ventricles)​
   ​
   ​Both important for memory, so perhaps memory does ‘grow’

Question 17

What is the principle of neurorehabiliation?

Answer 17

The clinical specialty that is devoted to restoration and maximisation of functions that have been lost due to NS injury.

Capitalises on the way the brain normally learns to relearn lost function.

Question 18

What is neural plasticity?

Answer 18

• Ability of the brain to change structurally and functionally as a result of input from the environment, normal phenomenon. Occurs at all levels of neuroaxis, from cellular to large scale cortical remapping.

Question 19

What is somatotopy?

Answer 19

Somatotopy is point-for-point correspondence of an area of the body to a specific point in the CNS.

Discrete areas of cortex:

• control motion of specific small groups of muscles
• receive sensation from specific areas of the body
• subserve vision from specific areas of the visual field
• subserve audition for specific pitches of sound

Question 20

What is the homonculus?

Answer 20

A graphical representation of the parts of the brain associated in with different parts of the body. You can see how some parts have greater representation than other and not directly correlated to acc body size.

Question 21

What can the brain representation be changed by - why is the homonculus not fixed?

Answer 21

Flexible and subject to neural plasticity - can be changed by

• Peripheral and central injury
• electrical stimulation
• learning + experience

Question 22

How do you fix the brain if you can’t grow new neurones?

Answer 22

• COMPENSATION - have one brain area take over functions of damaged area, simples neural recovery : uninjured tissue takes over function of lost neurones.
• Presynaptic neurons sprout more terminals, they form additional synapses with their targets and postsynaptic neurones, also add more receptor cells
• Reorganisation - a more dramatic form of neural recovery, can involve major brain areas.

Question 23

What is Constraint-Induced Movement Therapy (CIMT)?

Answer 23

Force patient to use their bad side by constraining their good side

Question 24

What is Transcranial Magnetic Stimulation?

Answer 24

Magnets produce field close to magnet, helps to release NTs that can help with neuroplasticity, can encourage certain pathways to recover.

Question 25

Are embryonic stem cells totipotent or pluripotent?

Answer 25

Totipotent - capable of giving rise to any cell type.

Adult stem cells are pluripotent - limited tissues (bone marrow, muscle, brain)

Question 26

What are brain-machine interfaces?

Answer 26

Used for neuroprosthetics - take signals from brain and processes them to apply them to interfaces.

Question 27

What’s the most widely used brain-machine interface?

Answer 27

The cochlear implant -> 200,000 people worldwide with sensoineural deafness now have these