The Pathophysiology of Ischemic Injury

Neurology Course 4th Year

Requirements For Adequate Cerebral Perfusion

• 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 • 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 ECF3. Biochemical changes 4. Ischemic brain edema

Mechanisms of Ischemic Injury

In general• loss of high-energy compounds • acidosis due to anaerobic generation of lactate • 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• 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 arterio-venous 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 hypothermia7) Induction of barbiturate sleep (decrease of brain metabolism)8) Inhibition of the inflammatory cascade