Lecture 24; Ischemic Brain Injury 1

Question 1

What is Brian ischemia?

Answer 1

Loss of blood supply to the brain
No oxygen or glucose delivery
Focal or global (CV failure)
Can occur at any stage of life

Question 2

What is the epidemiology of ischemic stroke in NZ?

Answer 2

3rd biggest killer -2500 people/ year
24 New Zealanders every day, a quarter < 65 years old
The leading cause of adult disability
Currently 60,000 stroke survivors in NZ, many with disability

Question 3

What are the causes of ischemic stroke?

Answer 3

• Atherosclerosis –fatty deposits lining vessel walls –restrict blood flow and clots can break off
• Thrombus -blood clot develops in a vessel in brain
• Embolism -blood clot develops elsewhere, usually in the heart or large arteries of the chest -breaks off and blocks small artery in brain
• Atrial fibrillation -clots form in the atria, dislodge and travel to the brain

Question 4

What is Neonatal arterial ischemic stroke observed?

Answer 4

symptoms observed after birth. MRI shows stroke occurred recently

However, is not normally diagnosed at the time until developmental stages are not met.
- Therefore less treatment options

Question 5

Are there treatments for pediatric ischemic stroke?

Answer 5

• No treatment

- Respond well to rehab b/c brain is very plastic

Question 6

What are causes 1-4 of PIS?

Answer 6

Congenital heart defects
sickle cell disease
immune disorders
diseases of the arteries

Question 7

What are causes 5-9 of PIS?

Answer 7

blood clotting abnormalities
head or neck trauma
intrauterine infection
premature rupture of membranes
maternal hypertension

Question 8

What feeds blood supply to the brain?

Answer 8

basilar or cerebral artery

Question 9

What are the two boundries of a stroke affected tissue?

Answer 9

• Ischemic core (infarcted tissue)

- Ischemic Penumbra (salvageable)

Question 10

How is the core and penumbra differentiated?

Answer 10

MRI –Use diffusion weighted imaging to calculate the apparent diffusion coefficient

Question 11

What happens to an MRI after stroke?

Answer 11

In acute cerebral infarction, the decrease in ADC values is the result of:Water moving into the intracellular compartment (diffusion is impeded by organelles)
Cellular swelling narrowing the extracellular space

Question 12

What is the penumbra?

Answer 12

Penumbra –reduced perfusion surrounding infarct
Suppressed protein synthesis, constrained ATP production (Injury progresses through the penumbra as ATP decreases)
Fundamentally reversible but time-limited

Question 13

What does penumbra injury or recovery depend on?

Answer 13

Depends on reperfusion and/or collateral perfusion

Question 14

What is collateral perfusion?

Answer 14

Other smaller arteries…

Question 15

What are two major collateral perfusion structures?

Answer 15

Circle of Willis: redistribute blood supply during extracranialvascular occlusion between carotid and vertebral arteries

Heubner’sanastomoses: determines volume and severity of focal ischemia during constriction of artery distal to Circle of Willis. Individual variability –number and diameter determines collateral supply

Question 16

What can be used to image the penumbra?

Answer 16

MRI Perfusion Weighted Imaging (PWI)

• Inject contrast (gadolinium)
• Measured parameters such as time to peak (TTP) or mean transit time (MTT)
• Measure of cerebral blood flow
• Reduced in penumbra and ischemic core
• PWI/DWI mismatch region approximately corresponds to the ischemic penumbra

Question 17

Whats a clot buster drug and when must it be used by?

Answer 17

TPA

- Must be used to treat within 3-4hrs to clear clot and restore blood flow
depends on collateral circulation

Question 18

Why is imaging important?

Answer 18

Ischemic vs haemorrhagic stroke
Clot busters (tPA)
Better response to clot busters when there is a large penumbra
Can administer TPA after 3 h if significant diffusion/perfusion mismatch
Infarcted tissue can’t be salvaged
Important for future therapies

Question 19

What is normal CBF and when does it become supressed?

Answer 19

Adult CBF ~ 50-70 ml/100 g/min CBF

~8 -18 ml/100 g/min = threshold for ion pump failure 

Brain activity is suppressed before threshold for ion failure

Question 20

At what point of CBF does fuel production change to anaerobic?

Answer 20

Anaerobic glycolysis

Glucose utilisation increases at 0.35mL/g/min (switching to anaerobic increases utilisation)

Declines below 0.25 mL/g/min

Accumulation of lactate and acidosis

Question 21

At what point CBF does Energy failure occur?

Answer 21

Energy Failure below 0.26 mL/g/min

Question 22

When does anoxic depolarisation occur?

Answer 22

Anoxic depolarisation below 0.10 mL/g/min

Question 23

What is anoxic depolarisation and how does it all fit in?

Answer 23

• Cells depolarise because of the lack of ATP to maintain membrane gradients.
• Tissues start to infarct at this point because cells swell and membranes become disrupted
• Release of neurotransmitters propagates this injury.

Question 24

What is happening in the penumbra?

Answer 24

Peri-infarct spreading depression:

• Depolarisation initiated in infarct core
• Spreads to peripheral zone
• Increased metabolic rate due to activated ion exchange pumps
• Reduced haemodynamic capacity of penumbra -mismatch between blood supply and demand
• Transient hypoxia and lactate production

Question 25

Describe the relationship between infarct size and depolarisations;

Answer 25

• Linear relationship between number of depolarisations and infarct volume

Question 26

What happens in global cerebral ischemia?

Answer 26

The whole brain becomes ischemic
May be the result of whole-body ischemia
Can occur at any stage of life
Perinatal asphyxia
Cardiac arrest
Severe hypotension (shock)

Question 27

What is the common cause of global adult ischemia?

Answer 27

Most often:
Primary ischemia + secondary hypoxia

Cardiac Arrest: 1/1000/year (20-75 y); only 20% of patients survive, and most survivors are disabled; 

Shock—-hypotension/hypoperfusion
Heart stops (arrests)
no cardiac output, hypotension

No blood flow to brain
AND no blood flow to lungs hypoxiaBrain ischemia + hypoxia

Question 28

What are the causes of global ischemia in the fetus?

Answer 28

Knot in umbilical cord
Compression of cord during labour
Umbilical cord around the neck
Maternal hypotension
Placental insufficiency
Cardiovascular collapse after birth

Question 29

What is the evolution of the global ischemia damage?

Answer 29

Evolves slowly over time after focal or global ischaemia

No core and penumbra pattern

Therapeutic windows of opportunity for treatment

Therapeutic hypothermia for HIE