CGS-19755 IS NEUROPROTECTIVE DURING REPETITIVE ISCHEMIA - THIS EFFECT IS SIGNIFICANTLY ENHANCED WHEN COMBINED WITH HYPOTHERMIA

In small animals the damaging effects of repetitive ischemia are more severe than a single insult of similar duration. Prolonged release of glutamate may correlate with the degree of damage. We report the protective effects of CGS-19755 (an N-methyl-D-aspartate receptor blocker), hypothermia or CGS-19755 in combination with mild hypothermia, in a gerbil model of repetitive ischemia. We used 3 min of forebrain ischemia and repeated it for a total of three times as 1-h intervals. Damage was assessed seven days after the insult. In the group where only CGS-19755 was used, significant neuronal protection was evident in the hippocampus (CA1 and CA3), striatum, and medial geniculate nucleus. With hypothermia significantly less damage was seen in the cerebral cortex, hippocampus (CA1 and CA4), and substantia nigra reticulata. When CGS-19755 was combined with mild hypothermia the effects of repetitive ischemia were completely abolished in all but one gerbil. Compared to hypothermia alone, significant protection was seen in the cerebral cortex, hippocampus (sibiculum, CA1 and CA4), striatum, medial geniculate nucleus, thalamus, and substantia nigra reticulata. The use of N-methyl-D-aspartate receptor blockers may protect the brain in repetitive ischemia. Combination with hypothermia may further enhance this protection.