Stroke Reperfusion Injury
Kesava Mandalaneni, Appaji Rayi, Dinesh Jillella
Abstract
Stroke is a major cause of death and disability worldwide, with a prevalence of about 2.5%. A stroke is called ischemic when caused by an interruption of the blood supply to the brain either through a blood clot called a thrombus or an embolus, which is a dislodged clot. At the onset of an acute ischemic stroke, lack of oxygen and other nutrients trigger a series of events causing electrophysiological, metabolic, and molecular damage, leading to irreversible brain tissue damage. The most proximal part of the arterio-vascular occlusion sustains maximal damage and is usually called an ischemic core. Between the ischemic core and normal brain tissue lies the 'penumbra,' an area of mild to moderate hypoxia that may become irreversibly damaged lest blood flow is restored to normal levels within a 'critical' time period. Without therapeutic interventions and continued ischemia, brain tissue death is quantified as a loss of 1.9 million neurons, 14 billion synapses, and 12 km of myelinated fibers every minute.In other words, one hour of ischemic brain damage can be compared to 3.6 years of normal brain aging. Acute stroke therapeutics aim to contain the tissue damage happening at the 'penumbra' level and restore the penumbra's functionality. Alteplase, a tissue plasminogen activator (tPA), is the only United States FDA (Food and Drug Administration) approved clot-busting medication used to recanalize the thrombosed / occluded vasculature in an ischemic stroke. Many studies have consistently shown better outcomes in acute ischemic stroke patients who received tPA. Intervention with tPA, newer proven endovascular interventions like mechanical thrombectomy aimed at recanalizing thrombosed vessels paradoxically may lead to deleterious consequences in the ischemic tissue due to many complexly woven biochemical and pathological events. In a subacute context, procedures like carotid endarterectomy and stenting may also lead to reperfusion injury. Such functional, microscopic, and sometimes a macroscopic injury consequential to blood flow restoration is termed as ischemia-reperfusion (I/R) injury.