Wk11 Damage And Repair In The CNS

Question 1

Head injury facts

Answer 1

• in 2013-14 there were 162,544 admissions for head injury
• admissions in uk with brain injury related diagnosis increased by 10% since 2005-6
• men are 1.6x more likely than females to be admitted for head injury

Question 2

Why is repair in the Injured CNS so complicated?

Cell to tissue

Answer 2

Proliferation and migration
Contact inhibition of proliferation 
Loss of neighbouring cells
Réactivation of neighbouring cells
Réactivation of proliferation
Tissue repair (damage accumulates)

Question 3

From multipotent cell to neuronal networks

Answer 3

Proliferation and migration
Neuronal differentiation —> synapse formation
Synapse plasticity —> altered connectivity and network reorganisation

Question 4

C1 to C8 functions affected

Answer 4

Cervical nerves
Head and neck
Diaphragm
Wrist extenders
Triceps and hand

Question 5

T1 to t12 functions affected

Answer 5

Thoracic nerves
Chest muscles
Abdominal muscles

Question 6

L1 to L5 functions affected

Answer 6

Lumbar nerves

Leg muscles

Question 7

S1 to S5 functions affected

Answer 7

Sacral nerves
Bowel
Bladder

Question 8

what do functional consequences of injury rely on?

Answer 8

Depend on the site and size of the injury not the type of injury

Question 9

Energy supply - brain

Answer 9

– 2% of the total body mass
– consumes 15% of the energy generated in the body
– no energy stores of its own (small amount of glycogen in astrocytes)
– energy is derived exclusively from glucose metabolism.

Question 10

Cerebral amyloid angiopathy and lobar hemorrhage

Answer 10

Alzheimer’s

Fibrous protein deposits become brittle leading to giant haemorrhage

Question 11

Arterio-venous malformations

Answer 11

Large number of dilated blood vessels with bad walls - can form embolisms

Question 12

Aneurisms

Answer 12

Blood coagulated over time - increased inter cranial pressure

Question 13

Lacunar infarcts and white matter damage

Answer 13

Tissue dies and leads to liquid filled hole

Question 14

Traumatic brain injury

Answer 14

• Impact - cerebral contusions and lacerations
• Movement of the brain inside the skull - subdural hematoma and diffuse axonal injury

Consequences:
• Hematomas (epidural and subdural ) – compression of the brain, raised intracranial pressure
• Contusions and diffuse axonal injury - structural brain damage
• Hypoxic injury, focal ischemic lesions
• Multiple lesions and different types of lesions

Question 15

Hypoxia - ischemic brain injury

Answer 15

– Drop in cerebral perfusion (Global ischemia) - cardiac arrest or severe hypotension (shock)
– Hypoxia - CO poisoning
– Hypoglycemia
– severe anemia
– generalized seizures

Question 16

Anoxic neurons

Answer 16

Differential sensitivity of different neuronal populations:
– Ischemia lasting 4-5 minutes – irreversible damage:
• hippocampal and neocortical pyramidal cells
• striatal neurons
• Purkinje cells
– More protracted ischemia – irreversible damage:
• thalamic and brainstem neurons

Question 17

Pseudolaminar and laminar necrosis

Answer 17

Selective vulnerability of different neuronal populations

Question 18

The progressive changes following a cerebral infarct

Answer 18

1-2 days tissue swelling Anoxic neurones
2 weeks tissue necrosis neovascularisation
2 months – glial scar

Question 19

Consequence of CNS injury

Answer 19

• Loss of cells and connections 
– Functional deficit
– BBB breach
• Response to injury
– Inflammatory response 
– Oedema
– Gliosis
• Long term consequences

Question 20

Traumatic brain injury

Answer 20

Long term consequences of severe TBI:
– Seizures
– Focal neurologic deficits
– Dementia
– Persistent vegetative state
– Increased risk of Alzheimer's disease.

Question 21

Features of CNS injury

Answer 21

CNS axons intrinsic capacity for regeneration

Inhibitory environment

• lack of neurotrophic stimulation
• neuronal death
• demyelination
• glial scar
• inhibitory molecules: associated with glial scar proteoglycans and associated with damaged mussel in Nogo, MAG, OMgp

Question 22

Treatment options for CNS injury

Answer 22

• Surgery
– remove a hematoma 
– repair skull fractures 
– decompression
• Medication
– Anti-seizure medication 
– reduce risk for seizures
– Reduce oedema 
– diuretics
– Induced coma 
- reduce oxygen and nutrient requirements
• Rehabilitation

Question 23

Types of recovery

Answer 23

• Neurological recovery
– Early recovery (Local Processes)
– Late recovery (Neuroplasticity) modification in structural and functional organization
• Functional recovery
– Recovery in everyday function with adaptation and training in presence/ absence of natural neurologic recovery
– Dependent on quality ,intensity of therapy & patient’s motivation

Question 24

Neuroplasticity Principles

Answer 24

1. Use It or Lose It
2. Use It and Improve
3. Specificity
4. Repetition Matters
5. Intensity Matters
6. Time Matters
7. Salience Matters
8. Age Matters
9. Interference

Question 25

CNS injury prognosis

Answer 25

• Most improvements in ADLs occurs during the 1st 6 months
• Up to 5% of patients may show improvement even at 12 months post- stroke
• Recovery could take 2 years or more
• Prognosis in patients with mild or moderate stroke is usually excellent

Question 26

Experimental strategies for treatment of CNS injury

Answer 26

• Trophic support
– Neurotrophic factors to neuronal cell bodies
• Inhibiting the inhibitors
– NOGO antibodies
– Digestion of GSPG – Chondroitinase 
– Rho inhibitors (siRNA)
• Endogenous stem cells
– Neurogenesis – subventricular zone, subgranular