Pathophysiology of brain injury and targets of treatment in acute ischemic stroke

Abstract

Brain is very vulnerable to ischemia, and exhibits various functional impairments in a flow-dependent manner. After onset of ischemia, the following cascade ensues propagating from the ischemic core to the surrounding area; ischemic depolarization, excitatory cellular injury induced by Ca2+ and glutamate, oxidative injury induced by reactive oxygen species including various free radicals, secondary microcirculatory disturbance, edema formation, apoptosis and inflammation. Intrinsic protective responses are also activated at the periphery of ischemic area. From the clinical view point, urgent detection of "penumbra" area by imaging modalities such as diffusion-perfusion mismatch and rescuing this area from evolving into irreversible damage (infarction) are the most important issues. Therapeutic targets in the acute phase of cerebral infarction consist of vascular therapy including acute thrombolysis, prevention of microcirculatory disturbance, protection of blood brain barrier and promotion of collateral blood flow, and cellular therapy such as neuroprotective measures aiming at neurovascular unit.