The Pathophysiology of Ischemic Injury
Neurology Course
4th Year
Requirements For Adequate Cerebral Perfusion
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Normal cerebral blood flow (CBF) in the range of 45-50 ml/min/100g
between a mean arterial pressure (MAP) of 60 and 130 mmHg
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Minimum MAP of 45 to 50 mm Hg is required to preserve cerebral viability
in man
Definition of Cerebral Ischemia
Main pathogenetic mechanisms:
1. microembolisation to brain vessels (due to myocardial infarction, mitral valve
damage)
2. stenosis of cerebral artery plus decreasing of systemic blood pressure
3. tromboembolism of large brain vessels
4. decreased cardiac output (due to decreased myocardial contractility, massive
hemorrhage)
Consequences of Cerebral Ischemia
1. Neurophysiological disturbances:
2. Changes in ECF
3. Biochemical changes
4. Ischemic brain edema
Mechanisms of Ischemic Injury
In general
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loss of high-energy compounds
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acidosis due to anaerobic generation of lactate
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no reflow due to swelling of astrocytes with compression of brain capillaries
Biochemical Events
Free Radicals
Mitochondrial Dysfunction
Lactic acidosis
Excitotoxins
The Concept of Ischemic Penumbra
autoregulation of blood flow is disturbed
 CO2 reactivity of blood vessels is partially preserved
 ATP is almost normal
 slight decrease of tissue glucose content (begining insufficiency of substrate
availability)
Clinical Definitions
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Stroke is defined as the clinical syndrome of rapid onset of cerebral deficit (usually
focal) lasting more than 24 hours or leading to death, with no apparent cause
other than a vascular one.
Completed stroke
Stroke-in-evolution
Transient ischemic attack (TIA)
Ischaemic stroke (CEREBRAL INFARCTION)
 Cerebral thrombosis (80%)
 Emboli
 Lacunar infarcts
Haemorrhagic stroke (SPONTANEOUS INTRACRANIAL
HAEMORRHAGE)
 Intracerebral (intraparenchymal) haemorrhage (10%)
 Another types of haemorrhage are usually caused by rupture of an arteriovenous malformation or angioma.
 Haemorrhages due to blood dyscrasia (eg. in association with leukaemia or
lymphoma) are of variable size and are often multifocal.
 Subarachnoid haemorrhage( 5%) : most commonly caused by rupture of a berry
aneurysm, usually situated at the junction.
Opportunities For Intervention
1) Cerebroprotective effect for a variety of calcium channel blockers administered post-insult
2) Free radical damage:
3) Phospholipase activation has been implicated as a significant source of injury
4) The importance of mitochondrial dysfunction
5) Protection against the deleterious effects of excitotoxicity –
6) Induction of mild hypothermia
7) Induction of barbiturate sleep (decrease of brain metabolism)
8) Inhibition of the inflammatory cascade