Pathophysiology of Acute Ischemic Stroke

In this article, we will discuss the Pathophysiology of Acute Ischemic Stroke. So, let’s get started.

Pathophysiology

A decrease in cerebral blood flow to zero leads to brain death within 4-10 minutes. Ischaemic stroke results due to occlusion of a cerebral artery or less often due to reduction in perfusion due to severely stenosed cerebral artery (atherosclerosis). When the cerebral blood flow is critically reduced below 20 ml/100 g/min, the resulting cerebral ischaemia without infarction unless prolonged for hours or days results in loss of neuronal electrical excitation due to failure of Na, K+ and ATP mechanism lead to cytotoxic oedema. This stage is reversible.

Further fall of cerebral blood flow to below 10 ml/100 g/min causes cerebral infarction with failure of cellular aerobic metabolism and lactic acidosis and ultimately death. This stage is irreversible.

Truely speaking, in any infarction, there is central core where the cerebral blood flow is drastically reduced (<10 ml/100 mg/min) which cannot be salvaged. A large area surrounds this area where cerebral blood flow is sufficiently reduced (between 10-50 ml/100 g/min) and the clinical symptoms are as a result of this reduction. The area is salvageable, if adequate timely intervention is done to improve the perfusion. This area is called ‘ischaemic pneumbra’ which can be rescued.  The area with blood flow of about 20 ml/100 g/min is salvageable, hence, efforts should be directed to improve circulation in this area to provide neuroprotection.

Therapeutic Time Window (window period): This is a period between reversible stage (ischaemic pneumbra) to irreversible stage of cellular death (homeostatic failure). This period is important from therapeutic point of view because intervention at this stage can protect the brain from damage (neuroprotection is possible). This window period is one to three hours which means that all intervention should be done within 3 hours and the earlier it is done the better are the results. However it is not possible to reach the hospital within this period soon after the stroke, some studies include patients up to 6 hours of stroke. It is estimated that about 50% pneumbra may still survive up to 72 hours.

Brain ischaemia and Free Radicals
Mediated Toxicity

Cellular ischaemia leads to cascade of free radicals mediated changes which are deleterious to the vital functions of tissues. Ischaemic depolarisation results in membrane failure and in an uncontrolled release of excitatory
neurotransmitters which are neurotoxic. A lot of substances such as prostaglandins, thromboxanes and leukotrienes are also released which are toxic to cell membrane causing lysis and generation of free radicals. The free radicals lead to neurotoxicity. An inflammatory response to ischaemic neuronal damage leads to elaboration of
interleukins, leucocyte adhesion, production of arachidonic acid and toxic free radicals formation.
Reperfusion either achieved by endogenous thrombolysis, thrombus migration or therapeutic intervention may aggravate ischaemic damage by production of toxic free radicals from reperfused tissue.

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