Basis of ionic dysregulation in cerebral ischemia

Stroke causes 9% of all deaths around the world and is the second most common cause of death after ischemic heart disease. Enhancing recovery from stroke and limiting ischemic damage are major goals to decrease stroke morbidity and mortality . Brain tissue is extremely sensitive to oxygen and glucose deprivation, and even brief ischemia can initiate a complex sequence of events that ultimately culminates in cellular death. Studies performed during the past 30 years have identified several key pathophysiological events that lead to ischemic neuronal degeneration. The pathophysiological processes in stroke are complex and involve disruption of the blood–brain barrier (BBB), energy failure, loss of cell ion homeostasis, acidosis, increased intracellular calcium levels, excitotoxicity, free radical-mediated toxicity, generation of arachidonic acid products, cytokine-mediated apoptosis, activation of glial cells, and infiltration of leukocytes . In focal cerebral ischemia, ischemic tissue is divided into an infarction core and penumbra. The core is the area of the brain where blood flow is reduced below 10–20% of its normal levels . In the core, rapid anoxic depolarization causes immediate loss of membrane potential followed by the loss of membrane integrity and rapid necrotic cell death. The penumbra is the tissue surrounding the core where the blood flow is partly preserved due to collateral circulation and diffusion .