WEEK 11 Flashcards
Give examples of the diverse group of CNS injuries
Spinal Cord Injury (SCI)
Traumatic Brain Injury (TBI)
Stroke
Brain Cancer
Which two examples of CNS injuries are people aged 15-24 most at risk to?
Spinal Cord Injury (SCI) and Traumatic Brain Injury (TBI)
Which two examples of CNS disorders are the older population more at risk to
Stroke and Brain Cancer
Describe how tissue repair occurs outside the CNS
Proliferation occurs, normal aging causes noxious influences, cell death (cell-cell contact), re-stimulates cell proliferation, tissue repair
What is the principle of tissue repair outside the CNS?
Complexity at expense of individual mortality
Explain how tissue repair in the injured CNS is so complicated
Proliferation occurs, neuronal differentiation=synapse formation, synapse plasticity=altered connectivity and network reorganisation, neurones not replaceable by cell division due to entire network being affected
What is the principle of tissue repair inside the CNS?
Complexity at expense of reparability
What is the meaning of topographical organisation of the CNS?
Different parts of the brain and spinal cord have different functions-anatomy and function are related
What is the effect of injury due to topographical organisation of the spinal cord?
Loss of movement, sensation and autonomic control below the level of injured segment
What is the effect of injury due to topographical organisation of the brain?
Different functions affected depending on which part of the brain is affected
What are the functional consequences of injury dependent on in the CNS?
The size and site of the injury, not the type
Describe the energy supply in the brain
2% of body mass, 15% of energy consumption, no energy stores of its own (small amounts of glycogen in astrocytes), energy is derived exclusively from glucose metabolism provided by the blood supply
What is the result of blood supply to the brain being affected?
Energy crisis due to unbalanced energy demand as a result of blood supply failing to deliver energy to the brain
Give six types of injuries to the brain
1) Skull fractures (eg. depression, open/closed, hairline, compression etc)
2) Hypertensive cerebral haemorrhage
3) Cerebral amyloid angiopathy and lobar haemorrhage
4) Arterio-venous malformations
5) Aneurysms
6) Lacunar infarcts and white matter damage
What is a hypertensive cerebral haemorrhage? look at image in notes
Hypertension causing filling of ventricular system with blood
What is a cerebral amyloid angiopathy and lobar haemorrhage? look at image in notes
Amyloid protein deposits in blood vessel walls, makes them brittle which allows for easy rupture
What are arterio-venous malformations? look at image in notes
A large number of dilated, malformed blood vessels which lead to bleedings
What is an aneurysm? look at image in notes
An enlargement of an artery caused by weakness in the arterial wall which increases intracranial pressure and increases risk of bleeding
What are lacunar infarcts? look at image in notes
Small infarcts (tissue death due to inadequate blood supply) in the deep cerebral white matter, basal ganglia, or pons
What can result from lacunar infarcts?
Vascular dementia
What are two components involved in Traumatic Brain Injury (TBI)?
1) Impact->cerebral contusions and lacerations
2) Movement of the brain inside the skull->subdural haematoma and diffuse axonal injury
What are the three consequences of Traumatic Brain Injuries (TBI)?
1) Haematomas (subdural and epidural)-compression of the brain, raising intracranial pressure
2) Contusions and diffuse axonal injury-structural brain damage
3) Hypoxic injury, facial ischaemic injury
What is the reason for hypoxic-ischaemic brain injury?
Energy supply to the brain is reliant on blood supply which is disturbed by TBI
What is Energy crisis?
When energy demand outruns supply
What causes energy crisis?
Drop in cerebral perfusion (Global ischaemia) due to cardiac arrest or sever hypotension (shock)
Hypoxia (oxygen deprivation) due to CO poisoning
Hypoglycaemia
Severe anaemia
Generalised seizures
What is the result of energy crisis?
Neuronal death
Why are different neurones affected differently by ischaemia?
Differential sensitivity of different neuronal populations
What is result of ischaemia lasting 4-5 minutes?
Irreversible damage to:
Hippocampal and neocortical pyramidal cells
Striatal neurones
Purkinje cells
What is the result of more protracted ischaemia?
Irreversible damage to:
all cells affected by shortened ischaemia + thalamic and brainstem neurones
What are anoxic neurones?
Neurones lacking oxygen supply
What are the progressive changes following a cerebral infarct?
1-2 days: tissue swelling, anoxic neurones
2 weeks: tissue necrosis, neovascularisation
2 months: glial scarring
Give the three categories of consequences of CNS injury
1) Loss of cells and connections
2) Response to injury
3) Long term consequences
What is the result of loss of cells and connections due to CNS injury?
Functional deficit and BBB deficit
What is the result of the response to injury due to CNS injury?
Inflammatory response
Oedema (BBB deficit)
Gliosis (proliferation of glial cells)
What are the long term consequences of CNS injury?
Sequelae of brain injury (other conditions)
Repair? (factors influence this)
What are the long term consequences of severe TBI?
Seizures Focal neurologic deficits Dementia Persistent vegetative state Increased risk of Alzheimer's disease
What is the difference between axonal regeneration in the PNS and CNS?
PNS: axonal regeneration present->macrophages clear debris, no inhibitory molecules present
CNS: no axonal regeneration->no macrophages to clear debris, inhibitory molecules present (reactive astrocytes up-regulate inhibitory ECM molecules inhibiting regeneration)
What is a characteristic of CNS axons that goes against the irreparable nature of the CNS?
They contain intrinsic capacity for regeneration
What reduces the CNS axons’ regenerative ability?
Inhibitory environment
What constitutes an inhibitory environment for regeneration?
Lack of neurotrophic stimulation Neuronal death Demyelination Glial scarring Inhibitory molecules
What are the two types of inhibitory molecules of regeneration?
1) Molecules associated with glial scar (proteoglycans-ie. CSPG)
2) Molecules associated with damaged myelin (ie. Nogo, MAG, OMgp)
Give the three types of treatment options for CNS injury
1) Surgery
2) Medication
3) Rehabilitation
What are different treatments for CNS injury involving surgery?
Removing haematoma
Repairing skull fractures
Decompression
What are different treatments for CNS injury involving medication?
Anti-seizure medication
Diuretics-reduce oedema
Induced coma-reduce oxygen and nutrient requirement
What is NeuroRehab?
A process whereby patients who suffer from impairment following neurologic diseases regain their former abilities or, if full recovery isn’t possible, achieve their optimum physical, mental, social and vocational capacity
What is early neurological recovery?
Recovery of local processes
What is late neurological recovery?
Neuroplasticity (modification in structural and functional organisation)
What is functional recovery?
Recovering in everyday function with adaptation and training in presence/absence of natural neurologic recovery
What is functional recovery dependent on?
Quality, intensity of therapy and patient’s motivation
What are the nine principles of neuroplasticity?
1) Use it or lose it
2) Use it and improve it
3) Specificity
4) Repetition matters
5) Intensity matters
6) Time matters
7) Salience matters
8) Age matters (decreases with age)
9) Interference
Describe the process of the neuroplasticity signalling mechanism
Neurotrophin synthesis->Neurotrophin secretion->Neurotrophin signalling->Postsynaptic responsiveness/Synaptic morphology/Presynaptic transmitter release/Membrane excitability=Modification of synaptic transmission and connectivity
What influences Neurotrophin synthesis/secretion/signalling?
Neuronal activity
Give the CNS injury prognosis
Most improvements in activities of daily living (ADL) occur in first 6 months but recovery could take 2 years or more
How is the prognosis in patients with mild or moderate stroke?
Usually excellent
Give four experimental strategies for treatment of CNS injury
1) Trophic support (neurotrophic factors)
2) Inhibiting the inhibitors (Nogo antibodies, digestion of GSPG, Rho inhibitors)
3) Endogenous stem cells (neurogenesis)
4) Cell therapy (replace dead cells, favourable environment, autologous stem cells)
