L22 - Damage and repair in the CNS Flashcards
Why is repair in the injured CNS so complicated?
- Complexity from cell to tissue at the expense of individual mortality
- Complexity from mulitpotent cell to neuronal networks at the expense of reparability
What does the severity of injury depend on?
Depends on site and size - not type of injury
What is the energy supply of the brain like?
- 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 glc metabolism
What are the 4 major types of skull fractures?
- Linear (most common) - break in a cranial bone resembling a thin line, without splintering, depression or distortion of bone
- Depressed - usually resulting from blunt force trauma; broken bones displace inwards
- Diastatic - widens the sutures of the skull and usually affects children under 3
- Basilar - break of bone in base of skull
What is hypertensive cerebral haemorrhage?
Hypertension causing arteries to rupture, therefore releasing blood into the brain tissue (type of stroke) –> lead to possible dec O2 supply to brain if compression of bleed is high
What is lobar haemorrhage?
Occurs when there is bleeding into a lobe of the cerebrum
- A subtype of intracranial haemorrhage
What is cerebral amyloid angiopathy?
- A condition in which amyloid proteins build up on the walls of the arteries in the brain
- Inc the risk for stroke caused by bleeding and dementia
- Accumulation of amyloid proteins in cerebral vessels
- Mutations in the APP gene are most common cause
What are arterio-venous malformations?
- A tangle of abnormal and poorly formed BV (arteries and veins)
- Arteries in brain cannot directly connect to nearby veins without having capillaries between them
- Higher rate of bleeding than normal
- Extreme press on walls of affected BV, causing them to be thin or weak
- Can rupture due to pressure and dmg to BV
- Can occur anywhere in the body
What are aneurysms?
- Enlargement of an artery caused by weakness in the arterial wall –> leading to bulge, distension of artery
- Often no symptoms
- Ruptured brain artery can be fatal –> subarachnoid haemorrhage –> can cause extensive brain dmg
What are lacunar infarcts?
- Small noncortical infarcts (a small localised area of dead tissue resulting from failure of blood supply) caused by occlusion (the blockage or closing of a BV) of a single penetrating branch of a large cerebral artery (smaller arteries supplying deep brain structures)
- Type of ischaemic stroke
What are the possible consequences of traumatic brain injury?
- Haematomas (epidural and subdural) - compression of the brain –> raises intracranial pressure
- Contusions and diffuse axonal injury
- Hypoxic injury –> focal ischaemic lesins
- Multiple lesions and different types of lesions
What happens in an energy crisis in the brain (? causes)?
- Drop in cerebral perfusion (global ischaemia) - cardiac arrest of severe hypotension (Shock)
- Hypoxia –> CO poisoning
- Hypoglycaemia
- Severe anaemia
- Generalised seizures
Which functions would be affected if the cervical nerves were damaged?
- Head and neck
- Diaphragm
- Wrist extenders
- Triceps and hand
Which functions would be affected if the thoracic nerves were damaged?
- Chest muscles
- Abdominal muscles
Which functions would be damaged if the lumbar nerves were damaged?
- Leg muscles
Which functions would be damaged if the sacral nerves were damaged?
- Bowel
- Bladder
What are the different types of haemorrhages?
- Epidural haemorrhage
- Subdural haemorrhage
- Subarachnoid haemorrhage
- Intracerebral haemorrhage
How could traumatic brain injuries occur?
- Impact - cerebral contusions and lacerations
2. Movement of the brain inside the skull - subdural haematoma and diffuse axonal injury
What is an epidural haemorrhage?
- Bleeding between dura mater and skull (calvarium)
- Biconvex shape (lemon shape)
- Limited by cranial structures, but not by venous sinuses
What is a subdural haemorrhage?
- Bleeding in subdural space; potential space between the dura and arachnoid mater
- Concave shape (crescent/ banana)
- Occurs more freq in elder patients due to reduced brain volume and stretched bridging veins
What is a subarachnoid haemorrhage?
Bleeding within the subarachnoid space
What is an intracerebral haemorrhage?
Bleeding within the brain tissue itself
- Stroke can occur from ischaemia
Typical cause of epidural haemorrhage?
- Assoc with history of head trauma and freq assoc with skull fracture
- Typically from torn middle meningeal artery
- Assoc with lucid interval (patient conscious and appears normal), as blood acc, headache will wrosen and mental status decline as intracranial press inc
Typical cause of subdural haemorrhage?
- Mainly due to head trauma
- Can happen to any age group
- Stretching and tearing of bridging cortical veins as they cross the subdural space to drain into an adjacent dural sinus
- These veins rupture due to forces when sudden change in velocity of head
Typical cause of subarachnoid haemorrhage?
- Ruptured aneurysm
- Head trauma
- AVM
Typical cause of intracerebral haemorrhage?
- Hypertension
- Head trauma
- Arteriovenous malformation
How could traumatic brain injuries occur?
- Impact - cerebral contusions and lacerations
2. Movement of the brain inside the skull - subdural haematoma and diffuse axonal injury
Can epidural haematomas cross suture lines and why?
Does not cross suture lines because of tight adherence of dura to calvarium (therefore resulting in biconvex shape)
Can subdural haematomas cross suture lines and why?
Can cross suture lines since bleeding is below the dura, which is tightly attahed to the calvarium (therefore leading to crescent shape)
What is pseudolaminar necrosis? (cortical laminar necrosis)
Necrosis of neurones in brain cortex in situations when O2 supply and glc is inadequate to meet regional demands
- Consequence of neurones being more metabolically active than glial cells or adjacent white matter
- Selective vulnerability of certain of different neuronal popns
What is a possible reason for the selective vulnerability in laminar necrosis?
Selective vulnerability of grey matter may be due to higher met demands and denser conc of receptors for excitatory aa that are released after an anoxic-ischaemic even
What is an anoxic brain injury?
- Not usually caused by blow to head
- Occurs when brain is deprived of oxygen –> if for too long, neural cells begin to die by apoptosis
What are some possible consequences to TBI?
- Neuronal death and tissue loss
- BBB breakdown and oedema
- Gliosis and cell infiltration
- Upregulation of inflammatory mediators
What are the progressive changes you can see in a cerebral infarct?
- 1 - 2 days tissue swelling –> anoxic neurones
- 2 weeks tissue necrosis –> neovascularisation (formation and remodeling of vessels - a response observed after injury)
- 2 months –> glial scar
What are the consequences of CNS injury?
- Loss of cells and connections
- Functional deficit
- BBB breach - Response to injury
- Inflammatory response
- Oedema
- Gliosis (nonspecific reactive change of glial cells; prolif or hypertrophy of several diff types of glial cells) - Long term consequences
- Sequela (future condition caused by this injury)
- Repair?
What are the long term consequences of severe TBI?
- Seizures
- Focal neurologic deficits
- Dementia
- Persistent vegetative state
- Inc risk of Alzheimer’s disease
Briefly explain the repair and regen of damaged neurones
PNS: Axonal regen present
- Macrophage clears debris after injury
- No inhib molcs present; extending growth core
CNS: No axonal regen
- No macrophage to clear debris after axonal injury
- Inhib molcs present
- BUT CNS NEURONES DO HAVE INTRINSIC CAPACITY TO REGEN - rehab is possible
What are some of the treatment options for CNS injury?
- Surgery
- Remove haematoma
- Repair skull fractures
- Decompression - Medication
- Anti-seizure med to red reisk
- Red oedema with diuretics
- Induced coma to red O2 and nutrient requirements - Rehabilitation
What is neurorehab?
A process whereby patients who suffer from impairment following neurological diseases regain their former abilities, or if full recov not poss, achieve their optimum physical, mental, social and vocational capacity
Describe the inhibitory environment found in CNS injury
- Lack of neurotrophic stimulation
- Neuronal death
- Demyeliantion
- Glial scar
- Inhibitory molcs (Assoc with glial scar and damaged myelin)
- Reactive astrocytes up-reg inhib extracellular matrix (ECM) molcs that inhibit regen
What is neurological recovery?
Early recov –> local processes
Late recov –> neuroplasticity; modification in structural and functional organisation
What is functional recovery?
- Recovery in everyday function with adaptation and training in presence/ absence of natural neurologic recovery
- Dependent on quality, intensity of therapy and patent’s motivation
What are the neuronal plasticity signalling mechanisms involved?
Neuronal activity –> neurotrophin synthesis –> neurotrophin secretion –> neurotrophin signalling –> postsynaptic responsiveness OR synaptic morphology OR presynaptic NT release OR memb excitability –> mod of synaptic transmission and connectivity
What are the neuroplasticity principles?
- Use it or lose it
- Use it and improve
- Specificity
- Repetition
- Intensity
- Time
- Salience
- Age
- Interference
What is functional plasticity of the brain?
Brain’s ability to move functions from a damaged area to other undamaged areas
What is structural plasticity of the brain?
Brain’s ability to change physical structure as a result of learning
What are some experimental strategies for treatment of CNS injury?
- Trophic support
- Neurotrophic factors to neuronal cell bodies - Inhibiting the inhibitors
- Endogenous stem cells
- Neurogenesis - Cell therapy
- Replace dead cells
- Create favourable enviro
- Bridge cyst cavities
- Autologous stem cells
