Lecture 20 – Brain Killers

Question 1

Brain killers:

Answer 1

¥ Neuronal damage/death
¥ Acute vs chronic
¥ Causes, treatments
¥ Understanding/research

Question 2

Brain:

Answer 2

¥	2-3% of body weight
¥	15% of cardiac output
¥	20% of all O2
¥	25% of all glucose
¥	Brain critically dependent on a constant blood supply

Question 3

An efficient transport system:

Answer 3

Because of the isolated nature of the brain from the rest of the body = central versus peripheral nervous system certain substances essential for normal brain function need to gain access – and waste/harmful products removed (severe cooling used to calm down the metabolism of someone having a stroke)

Question 4

Stroke risk factors:

Answer 4

¥

Atherosclerosis – fatty deposits causing clots
¥ Age – older people at higher risk
¥ Diabetes (doubles the risk) – rapid changes in glucose available
¥ Ethnic origin (more common in African-Caribbean people)
¥ Excessive alcohol
¥ Family history of stroke – cardiac vessels and vessels supplying the brain have the same mechanisms
¥ Heart disease
¥ High blood pressure - hypertension
¥ High blood cholesterol – statins control this
¥ Obesity & inactive lifestyle
¥ Smoking

Question 5

Damage caused by a stroke: (large blood vessel)

Answer 5

• 2 million brain cells lost after the initial major blockage due to loss of oxygen
• 14 billion connections gone
• 7.5 miles of wiring destroyed

Question 6

Causes of ischaemic stroke:

Answer 6

Stroke is a vascular disease, but not necessarily a cerebrovascular disease
50%: athero-thrombo-embolism cerebral arterial supply which a large portion comes from the heart
20%: embolism from heart - atrial fibrillation is when the heart begins to beat irregularly causing a pool of blood to build up in the heart which increases the risk of clotting – leading to a stroke
25%: intracranial small vessel disease – arterioles in the brain are blocked congenitally due to atherosclerosis (this is now an active process – full of neutrophils and macrophages that can release toxins leading to damage after a stroke)
5%: rare causes

Question 7

types of strokes

Answer 7

Type 1: Ischaemic stroke – vessels becomes blocked and most common
Type 2: haemorrhagic stroke – vessel bursts

Question 8

TPA

Answer 8

enzyme which breaks up fibrinogen in clots, first used to treat heart attacks to unblock the clot, now applied to strokes.
If TPA is given to someone who is suffering from a bleed rather than a clot it will make things worse, if given too later after a stroke then the reflow of blood can get worse (must be given within 3-4 hours).

Question 9

Development of ischaemic damage:

Answer 9

• core is levels of low blood flow and this is the most damaging
• brain can withstand this low blood flow for a short period of time only
• the blood supply is higher – the penumbra (supplied by other blood vessels – one blocked, another will try to maintain)
• core is dead tissue and penumbra is vulnerable tissue in high blood flow areas
• neurons from the core (damaged tissues) release toxins that start to kill brain cells

Question 10

¥

Neurotransmitters

Answer 10

Ð glutamate – needed for memory (highly toxic and released in very small quantities)
Ð problems occur as the pumps can be defected and cannot pump glutamate back into the cell making the synaptic cleft a toxic region

Question 11

¥ Ions

Answer 11

Ð calcium, sodium
Ð changes in ion concentration expected with depolarisation
Ð this is to create AP
Ð after strokes, there’s a reduction in oxygen so a reduction in oxygen, thus the levels become quite acidic and sodium and calcium levels rise (protons)

Question 12

¥ Free radicals

Answer 12

Ð abnormal oxygen molecules e.g. superoxide

Ð nitroxide has beneficial and detrimental affects

Question 13

excitotoxicity

Answer 13

excitotoxicity leads to depolarisation which leads to potassium channels opening and an action potential which causes the normal stuff

Question 14

Reperfusion injury:

Answer 14

¥ Restoration of blood flow to an area of the brain previously rendered ischaemic by a thrombotic blockade of a key artery
¥ Caused by lysis or dislodgement of the clot
¥ Results in inflammation and oxidative stress (more free radical formation)

Question 15

Post stroke disabilities: (CT/ MRI scans taken)

Answer 15

¥ Paralysis/motor control – inability to control limbs well so physiotherapy is used
¥ Sensory disturbance (pain)
¥ Language problems
¥ Memory impairment – short term memory impaired but long term stays in tact but usually depends on the site of the injury
¥ Depression/anxiety and fatigue – very common, very tired
¥ Can cause another stroke if the causes are not dealt with (exercise etc)

Question 16

Reparative mechanisms:

Answer 16

1. Plasticity
2. Neurogenesis
3. Angiogenesis

Question 17

FUTURE:

Answer 17

• Combination treatments

- Strategies to promote recovery