Stroke Flashcards
Acute neurodegenerative disorder
Stroke
Chronic Neurodegenerative disorder
Alzheimer’s, Parkinson’s
Cerebral stroke
- Blockage/interruption of cerebral artery
► Death of cells
Prevalence in the UK
- 250-400 strokes per 100 000 people
- 3rd cause of death
- 1st cause of disability (in adults)
Types of stroke
Ischemic
Haemorrhagic
Ischemic stroke
Occurs when blockage within blood vessel stops/reduces flow
Blood clot formed within the vessel
Haemorrhagic stroke
Area of bleeding as blood vessel bursts
High blood pressure
cerebral arteries under pressure
May experience aneurism
Risk of stroke
At all stages of lifespan
1 in 4 strokes occur in working age adults
Risk factors
Age
Medical conditions (High blood pressure, diabetes, atrial fibrilation, high cholesterol)
Lifestyle (smoking, drinking, diet)
Family history and ethnicity
Specific for women (pregnancy, contraceptive pill)
Consequences of stroke : clinical symptoms
Sudden or gradual onset
One-sided limb weakness/paralysis
Confusion, loss of speech/vision
Headache
Loss of consciousness
= results in dysfunctional cognitive and motor behaviour determined by size and location of cell loss
cognitive impairment of stroke
Amnesia
Inattention
Confusion
Depression
Mood and behaviour changes
Depression due to stroke
Common after a stroke
Not simply a consequence of physical effects
Patients with post-stroke depression (PSD) differ from those with primary depression in that they have more cognitive impairment, irritability, more psychomotor slowing and more mood liability
pathology of stroke
- Transient episode of neurological dysfunction without acute tissue death
- Disruption of CBF
- Mini-strokes
- Risk factor for subsequent stroke
- 10% strokes within 90 days of TIA
- Silent strokes
- No visible symptoms
Cerebral stroke - pathology
Massive cell death
Ischemic lesion
Cascade of further complex events
Inflammation
Massive cell death
Primary cause of cell death is excessive amounts of glutamate
Cascade of further complex events
inflammation, cell death, reperfusion
trying to reestablish blood flow
Inflammation
- Sodium ions – water, swell, inflammation
- Microglia – become phagocytic
- Phagocytosis = ‘cell-eating’
- Blood-brain barrier breakdown – influx of blood-borne immune cells (neutrophils, macrophages)
- Oedema formation, adhesion molecules, cytokines
2 mechanisms of cell death
Necrosis and Apoptosis
Necrosis
Lower in oxygen
Depleted ATP
Cellular swelling and membrane break down
Apoptosis
= triggering of death programme
intracellular signalling
cells fragment into vesicles
phagocytosis by neighbouring cells
Cerebral stroke- reperfusion injury
- Hyperperfusion
- A major increase in cerebral blood flow (CBF), well above metabolic demands of CNS tissue
- Complication of surgical intervention
- E.g. intracranial stenting
- Intracranial haemorrhage/edema
- Mortality 36-63%
- 80% patients significant morbidity
- Damage to the blood-brain barrier
Excitotoxicity
- 1957 Lucas & Newhouse reported that s.c. glutamate caused retinal damage
- 1969 Olney reported that glutamate produced brain damage in neonatal mice
- Ultrastructural studies
- amino acid treatment = postsynaptic (but not presynaptic) alterations
- Excitotoxic hypothesis
- Excess amino acids results in prolonged depolarization of receptive neurones which in some way* leads to their eventual damage or death
GABA system
- GABA system – functions in opposite to glutamate
- During ischemia
- GABA accumulates in extracellular space
Cerebral stroke treatments
- Pharmacological
- Thrombolysis - breaks down clots
- Aspirin
- Modifiable risk factors
- Physiotherapy
Drugs and receptors
- Drugs have effects and sites of action
- In the CNS, they alter synaptic function
Increase or decrease action of neurotransmitter
Pharmacological treatments
Neuroprotection
- aims to protect neurons from injury
- limited by therapeutic time window and effectiveness
NMDA receptor antagonists
- proved to be most successful in protecting against cell death
ALL clinical trials failed
Thrombolysis
Tissue Plasminogen Activator (t-PA)
- 3 hours
- CT scan
Surgical intervention
Intra arterial thrombolysis
TO BREAK UP BLOOD CLOTS
Aspirin
- Antiplatelet agents (and anticoagulant)
- Prevention of recurring strokes
- Reduction of severity of stroke
- Inhibit production of thromboxane (decrease natural levels of blood clotting)
An ischemic stroke occurs as direct consequence of
A blockage in a blood vessel
Within the penumbral area of a ischemic stroke…
Blood flow is sub-optimal and tissue is salvagable
What is a common cellular process which results in apoptosis during ischemic stroke
Caspase activation
