5. Injury And Potential For Recovery In CNS

Question 1

What does the CNS contain?

Answer 1

Brains and Spinal cord only

Question 2

What does the PNS contain?

Answer 2

• cranial nerves (except cranial nerve II), ganglia and spinal nerves
• it’s also different to the way it recovers

Question 3

What types of injuries are there to the CNS?

Answer 3

• developmental
• traumatic
• ischaemic (e.g. stroke)
• hypoxia (e.g. cardiac arrest)
• inflammatory (e.g. multiple sclerosis)
• neurodegenerative (Parkinson’s, Alzheimer’s)
• infection (e.g. meningitis), tumours

Question 4

Most types of injury affects all brain cell populations, what are the types?

Answer 4

• neurones, glial cells (astrocytes, oligodendrocytes, microglia), blood brain barrier and CSF

Question 5

What is a stroke?

Answer 5

• acute loss of blood supply, usually by occlusion of artery
• 6-8min of blood supply being interrupted (due to ischaemia or haemorrhage) -> to cause neuronal death (an infarction)
• most cerebral vascular occlusion will reopen spontaneously within 24h but for neurones that’s too late

Question 6

What is hypoxic brain injury?

Answer 6

• decrease in oxygenation in whole brain
• after cardiac arrest -> heart stops -> BP too low to little BF to brain (whereas stroke is where a region of the brain deprived of O2)
• area’s most metabolically active is most affected by this type of injury (grey matter (cell bodies) like cerebral cortex, basal ganglia)

Question 7

What is MS?

Answer 7

• autoimmune
• inflammation of myelin sheath
• demyelination of neurones -> neuronal dysfunction
• white patches = suggestive of MS
• only ogliodendrocytes

Question 8

What is neurodegeneration?

Answer 8

• shrinkage of brain

- white lines in brain -> meningitis

Question 9

How can neurones be damaged?

Answer 9

• severed

- lose input

Question 10

What happens to axon when neurone damaged?

Answer 10

• Upstream - retrograde degeneration: cell body die via apoptosis
• downstream - anterograde degeneration: distal axon does via Wallerian degeneration

Question 11

What is a consequence of the neurone denervation?

Answer 11

• if nerve damaged then what happens distal nerves in different, common in SC injury:
• • get spasticity -> inc tone that’s velocity dependant bc of hypersensitivity that occurs due to denervation
• • degeneration of target cell, commonly seen in the visual system so if damaged eye, injure optic tract -> degeneration in lateral geniculate nucleus

Question 12

Do nerves regrow?

Answer 12

• severed axons in PNS can regrow if myelin sheath intact will
• cleanup by macrophages, regrowth by Schwann cells (cleanup is important-> if fast then helps regeneration)
• but cleanup is slow in CNS and oligodendrocytes tend to inhibit regeneration, the environment is not optimal for regeneration so CNS ≠ regenerate

Question 13

What do we mean by regeneration?

Answer 13

regrowth of severed axons
Occurs in non mammalian vertebrates
Effectively occurs in mammals in PNS only

Question 14

Why is myelin so important for regeneration?

Answer 14

Critically important for the process
Provides a guide tube for sprouting of a severed axon to go through and can guide neurone to its destination as it develops

Question 15

What are the different grades of nerve injury and prognosis for each?
(look at ss of the different grades to familiarise what each looks like)

Answer 15

Grades:
1 - Neuropraxis - conduction disruption with axon intact and preserved supported structures
prognosis: normally full recovery days-weeks w/ no surgical interventions
2 - Axonotmesis - disrupted xon with intact endoneurom. Wallerian degeneration after 1-2 weeks
prognosis: variable recovery, worse prog for proximal injuries or injuries with doesn’t re-implant into muscle within 18 months
3 - Neurotmesis (III) with preservation of perineurium - disruption to supporting structures, endoneuirm disrupted
prog: 60-80% recovery
4 - Neurotmesis (IV) with preservation of epineurium
prog: nerve grafting required
5- Neurotmesis (V) with complete transection of nerve trunk
prog: bypass/jump grafting required

Question 16

What is glial scarring

Answer 16

after nerve injury –> proliferation of astrocytes and microglia (reactive cellular process) –> glial scar formation (gliosis)

Question 17

What is the purpose of glial scarring

Answer 17

• to protect and be part of the healing process
• helps regenerate a tissue barrier after blood brain barrier has been compromised, promotes revascularisation of the brain after injury to it
  but in context of a neuronal injury, this can negative effects too

Question 18

What is neurogenesis and where can it be found in mammals? What is the significance of these areas?

Answer 18

-birth of new neurones
-adult mammal brain prod few new neurones but evidence found in 2 areas:
- hippocampus (dentate gyrus)
- near the lateral ventricles (sub-ventricular zone) supplying the olfactory bulb
both areas important for memory so perhaps memory does grow and it occurs via stem cells

Question 19

What is neurorehabilitation

Answer 19

referring to clinical speciality which is devoted to restoration and maximisation of functions that have been lost due to NS injury

most neuro injury are irreversible and cannot be cured but you can treat by dec severity and freq of attacks

Question 20

What is rehabilitation mainly about? and how does this link to neurorehabilitation

Answer 20

• is learning
• everything we learn is hardcoded in our brain by change in synaptic strength in some area of the brain
• neurorehab uses the way the brain normally learns to relearn lost function –> approach to this using learning, alone and in combination w/ other therapies promotes advanced neural plasticity

Question 21

what is neural plasticity

Answer 21

ability of the brain to change structurally and functionally due to inputs from the environment

this is a normal phenomenon underlying brain function is widepread to all parts of brain (sensory, visual, language, motor etc.)

scans of student brains found changes in brain w/ inc met in certain parts of brain –> structural changes that inc over time as they study

Question 22

what is somatotopy? what is a homunculus (look at ss)?

Answer 22

refers to parts of the brain correspond to specific function/point of point correspondence of an area of the body to a specific point in the cns
homunculus is a graphical representation of parts of the brain associated w/ diff parts of the body - hand has lots of dexterity so representation of hand in motor cortex is v big to be able to do subtle movements and this is same w/ the mouth and speech

Question 23

are all actions/tasks specific to one area

Answer 23

no, some tasks are shared so not always specific to just one area
there is flexibility of brain and changes are subject to neural plasticity which can be changed in perip or central injury, electrical stim and learning and experiences –> e.g. violin player –> inc cortical rep of left hand finger so homunculus not fixed

Question 24

how is the brain fixed/repaired if neurones can’t regrow? what are some evidence of neural plasticity after brain injury

Answer 24

1. though compensation –> having one brain area take over the functions that damaged area was doing –> simplest neural recovery where uninjured tissue takes over the functions of lost neurones
2. presynaptic neurones may sprout more terminal –> this forms additional symapses w/ their targets and post synaptic neurones
3. can be addition of more receptor cells to inc sensitivity
4. can be reorganisation of brain –> this is a more dramatic form of neural recovery and can involve major brain areas

we know neural plasticity exists from functional mri scans (in patients with stroke that are able to move their stroke affected hand, evidence showed that the side of the brain not stroke affected lights up in the scan. even in movement of unaffected hand the organisation is still diff)

neural plasticity after brain injury:
in children w/ epilepsy, do a hemispherectomy (remove half of brain) and they won’t become hemiplegic and outcome can be surprisingly good w/ language reorganisation and relative intellectual preservation.
we do see recovery of function after stroke which shows power of neural plasticity

Question 25

how are some ways of recovering brain injuries ?

Answer 25

CIMT (constraint induced movement therapy):
force stroke victim to use affected side –> can drastically improve function in motor function

TMS (transcranial magnetic stimulation):
put mag field th/ brain –> prod electric currents which enhances ability to grow nerve cells

Question 26

what are the two main types of stem cells

Answer 26

embryonic stem cells - totipotent - can become any cell type
adult stem cells - pluripotent - not all cells but still many diff cells - get them th/ umbilical cord/placenta and bone marrow

Question 27

what is iPSC

Answer 27

• inducing pluripotent stem cells

- reprogramming mature cells to become stem cells

Question 28

What happens in stem cell transplantation

Answer 28

transfer stem cells into injured part of NS
not a lot of evidence that putting stem cells into right place= they turn into neurones, but something is happening
this is bystander effect: fact that stem cells are present are having some sort of effect which are:
- anti inflamm
- anti apoptopic
- neuroprotective
- aiding trophic factors and overcoming natural inhibitors

Question 29

what is brain machine interface

Answer 29

if cannot regenerate brain and fufill recovery we were hoping, must try and get brain signals to become movement we want

this is the idea of having an interface b/w brain and computer

• brain sends a signal which is detected by a detector which sends signal to an electronic device to perform function
• this is most widely used in cochlear implants