Inhibitory mechanisms in cerebral ischemia: a brief review

Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of energy loss, excessive excitation promoting intracellular Ca2+ buildup, relative lack of inhibitory responses, generation of oxygen free radicals, especially during the reperfusion period and several other destructive cascades. Therapies aimed at decreasing the ill effects of glutamate are either not effective or have serious side-effects. Ca2+ entry blockers are generally not effective in cerebral ischemia, and data with protective effects of oxygen free radical scavengers in the post-ischemic period have shown conflicting results. There is recent interest with the use of agents that increase cerebral inhibitory responses after an ischemic insult. Such agents are effective when used before, during or up to 4 h after the ischemic insult. Many such medications have few side-effects and are in clinical use for other indications. This review will summarize inhibitory mechanisms that may be important in cerebral ischemia, and provide experimental evidence for their potential efficacy.