L20 - Brain Killers II

Question 1

Inflammation (5)

Answer 1

o	Heat (calor)
o	Redness (rubor)
o	Swelling (tumor)
o	Pain (dolor)
o	Loss of function (functio laesa)

Question 2

Inflammatory mediators

Answer 2

• Glial cell activation (astrocytes, microglia)
• Oedema – causes increase pressure in the brain
• Systemic acute phase response
• Expression of adhesion molecules
• Invasion of immune cells
• Synthesis of inflammatory mediators
o Cytokines, free radicals, prostaglandins

Question 3

What are Cytokines (production and target)

Answer 3

• Small proteins involved in all forms of disease and injury
• Don’t find them in healthy cells
• INTERLEUKINS/INTERFERONS/TUMOUR NECROSIS FACTORS/“GROWTH” FACTORS/CHEMOKINES
• Produced by damaged cells
• Acts on the brain
• Communicate between cells

Question 4

Cytokines in stroke (source and main one?)

Answer 4

• Can be produced in the brain
• Particularly after brain injury
• Microglial cells are a main source
• Interleukin-1 particularly important

Question 5

Effects of cytokines in the brain

Answer 5

• 1000x more potent in the brain than the site of infection.

Question 6

use of a Fever

Answer 6

• Heat kills bacteria

Question 7

What is Interleukin-1 (IL-1)

Answer 7

• Master cytokine’
• Key inflammatory mediator
• Major disease target
• Produced rapidly in the brain
• Naturally occurring and highly selective antagonist, IL-1Ra

Question 8

IL-1 mediates brain injury (what happens when we inhibit?)

Answer 8

• Rapid up regulation of IL-1α, IL-1β, IL-1Ra spatial temporal pattern consistent with contribution to injury

• Exogenous or endogenous IL-1 enhances brain injury
• Inhibition of IL-1 markedly inhibits injury

Question 9

Inflammatory burden & stroke

Answer 9

• Reduce inflammation = reduce stroke

Question 10

Inhibition of IL-1 reduces: 6

Answer 10

• Focal, global, permanent, reversible ischaemia
• Traumatic injury
• Excitotoxic damage (NMDA, AMPA/KA)
• Clinical symptoms of EAE
• Heat stroke damage
• Epileptic seizures

Question 11

Cellular targets of IL-1

Answer 11

• Neurones
• Glia
• Endothelial cells

Question 12

IL-1 actions – peripheral or central?

Answer 12

• Systemic inflammation linked to cardiovascular disease
• IL-1 expression peripherally induces CNS responses
• Neural and hormonal
• Rapid IL-1 production in brain after acute insults

Question 13

Systemic inflammation & stroke

Answer 13

Inury causes more inflammation, which acts as positive feedback.

Question 14

Beneficial effects of IL-1

Answer 14

Increased GF

Question 15

DETRIMENTAL EFFECTS

Answer 15

Activation of glia release toxin

Direct effect on neutrons

Cerebrovascular actions

Question 16

Phases of treatment

Answer 16

Phase 1 – healthy individuals (volunteers)

Phase 2 – is it safe in patients you look to treat (not healthy imdv)

Phase 3 – more patients (more sick)

Phase 4 - monitor use

Question 17

Subarachnoid haemorrhage

Answer 17

Blocking in brain / similar to stroke

Insert coil in brain and block bleeding