Brain protection against ischemic injury by nizofenone.

Abstract

Ischemic brain injury is induced in a complex and multifactorial pathogenic cascade; but the fundamental mechanism is the imbalance between energy demand and supply in ischemic brain tissue. Nizofenone is a potent neuroprotective drug which ameliorates this imbalance and also various pathophysiologic events during ischemia, such as ATP depletion, lactate accumulation, glutamate release, free fatty acid liberation, edema, and neuronal degeneration; in particular, ischemia-induced excessive glutamate release has been completely blocked by this drug. This drug has also radical-scavenging action, comparable to vitamin E, and inhibits oxygen radical-induced lipid peroxidation. The potent cerebroprotective effect of nizofenone has been demonstrated in various experimental models of cerebral hypoxia, ischemia (focal and global), ischemia-reperfusion, and infarction. The clinical efficacy of nizofenone has been proved by pioneering double-blind studies in acute subarachnoid hemorrhage patients. Nizofenone is clinically used for preventing the delayed ischemic neurologic deficits due to late vasospasm following subarachnoid hemorrhage. In this report, the property of the cerebroprotective effect and the clinical efficacy of nizofenone is reviewed.