Lec 12 (B)- Stroke

Question 1

Stroke

Answer 1

• Stroke is characterised by rapidly developing symptoms and signs of focal or global loss of cerebral function lasting more than 24 hours or leading to death
• Third most common cause of death in developed countries
  
  • Half of all strokes occur in people +70yrs old but can occur in all ages
• 2 main types, Ischaemic and Haemorrhagic
• >80% are ischaemic

Question 2

Risk factors

Answer 2

• Previous mini-strokes
• High BP
• Diabetes
• Heart disease
• Smoking
• Obesity-increased cholesterol

Question 3

• Sudden numbness or weakness in the face, arm or leg especially on one side of the body (FAST campaign)
• Sudden confusion, trouble speaking or understanding
• Sudden problems seeing in one eye or both eyes
• Sudden dizziness, loss of balance or coordination, or trouble walking
• Sudden severe headache with no known cause

Question 4

Ischaemic vs Haemorrhagic

Answer 4

• Interruption of blood flow to a brain region- ischaemia, reduces oxygen and glucose supply, leading to cell death

Question 5

Causes- Ischaemic stroke

Answer 5

• Thrombosis in cerebrovasculature
• Deep Vein Thrombosis
• Blood clots in the heart- Atrial Fibrillation
• Atherosclerosis
• Blood inflexion- Bacterial clumps
• Injecting illicit substances

Question 6

Causes- Haemorrhagic stroke

Answer 6

• Increased blood pressure
• Diseased blood vessels- uncontrolled diabetes
• Tumours
• Blood clotting deficiencies

Question 7

Stroke- the cascade of damaging events

Answer 7

Question 8

Excitotoxicity

Answer 8

• Glucose and O₂ delivery stop during a stroke
• Neurons become depolarised (Anoxic depolarisation)
  
  • Increased glutamate release
  • Decreased glutamate re-uptake
  • K⁺ efflux
  • Ca²⁺ overload
  • Activation of proteases, endonucleases, NOS etc
  • Na⁺ and Cl^- enter the neurones- bringing water too (osmosis)
  • Peripheral areas now affected by oedema- can cause more ischaemia through vascular compression
  • Reperfusion injury- when blood and O₂ return, neurones are hyperactive- more excitotoxicity injury

Question 9

Excitotoxicity- Anoxic LTP (Long Term Potential)

Answer 9

• Massive Ca²⁺ influx during ischaemia activates LTP processes
• Leads to huge increase in excitatory synaptic strength
• Drives a second wave of excitatory during reperfusion of ischaemic area

Question 10

Anoxic depolarisation

Answer 10

Question 11

Peri-infarct depolarisation

Answer 11

• Neurons in ‘core’ region never repolarise
• Those in ‘Penumbra’ repolarise, but this costs energy (ATP)
• In the penumbra- cells repeatedly de- and repolarise as they cycle between energy depletion and using up available energy
• Several PID per hour, lasting 6-8 hours
• Leads to more excitotoxic death

Answer 12

Question 13

Inflammation

Answer 13

Question 14

Apoptosis

Answer 14

• Most cells (esp. in core) die via necrosis
• Apoptosis= cell ‘suicide’
  
  • Occurs in milder injury zones- penumbra
  • Gene-activated process
  • Cyt C moves from mitochondria to cytoplasm
  • Cyt C forms the ‘apoptosome’ with other proteins
  • Apoptosome activates caspases