AMPLIFICATION OF INHIBITORY MECHANISMS IN CEREBRAL-ISCHEMIA - AN ALTERNATIVE APPROACH TO NEURONAL PROTECTION

The central nervous system consumes 20% of the cardiac output for norm al function. The neurons are very sensitive to the effects of ischemia . Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of ene rgy loss, excessive excitation promoting intracellular calcium (Ca2+) buildup, relative lack of inhibitory responses, generation of oxygen f ree radicals (especially during the reperfusion period) and several ot her destructive cascades. Medications that antagonize the effects of g lutamate at post-synaptic receptors are either ineffective or have ser ious side-effects. Ca2+ entry blockers have shown disappointing result s in clinical trials in patients with acute cerebral infarction. Data with protective effects of oxygen free radical scavengers in the post- ischemic period have shown conflicting results. There is recent intere st 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 hours after the ischemic insult. Many such medicatio ns have few side-effects and are in clinical use for other indications . This review will summarize inhibitory mechanisms that may be importa nt in cerebral ischemia, and provide experimental evidence for their p otential efficacy.