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.