Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage

Strokes result when ischemia (oxygen deprivation due to reduced blood flow) in the brain causes irreversible damage to nervous tissue. However, the ischemia is only the first step in a complex sequence of events which leads to irreversible damage. Although many pathologic changes occur in an environment of reduced oxygen, some researchers feel that the event leading directly to the death of neurons is the accumulation of calcium within the cell. Free calcium ions can accumulate within the cell by two basic mechanisms, the entry of calcium through receptor-operated channels, and entry through voltage-sensitive channels. Efforts to develop methods to reduce the rate at which irreversible damage occurs in starved brain tissue focus on blocking the entry of calcium into brain cells via these two pathways. In this research using an animal model (the cat) of ischemic brain damage, investigators tested the effects of nimodipine, a drug which blocks voltage-sensitive calcium channels, and MK-801, an antagonist of the neurotransmitter NMDA which blocks NMDA-receptor-operated calcium channels. While both MK-801 and nimodipine individually reduce the pathologic effects of ischemia somewhat, together the drugs are more effective. In the cats, the combination improved physiological measures of brain function, and also reduced the area of brain damaged by ischemia by more than a factor of five. The combination of the two drugs would seem to be a useful tool in the reduction of permanent damage resulting from brain ischemia. (Consumer Summary produced by Reliance Medical Information, Inc.)