THE EFFECT OF POSTISCHEMIC HYPOTHERMIA FOLLOWING REPETITIVE CEREBRAL-ISCHEMIA IN GERBILS

Repetitive ischemia may result in more severe damage than a single sim ilar duration insult. Inter-ischemic hypothermia significantly decreas es this damage. It is unclear if protection would be evident if coolin g was delayed until after the repeated insults. In this study, we eval uated the effects of 3 h of mild cooling (34-35 degrees C) beginning i mmediately after the third insult of ischemia, 0.5 h after the third i nsult and 1 h after the third insult in a gerbil model of repetitive i schemia. Neuronal damage was assessed in the cerebral cortex (CTX), hi ppocampus (CA1, CA4), striatum (STR), thalamus (THL), medial geniculat e nucleus (MGN), and the substantia nigra reticulata (SNr). A '4-point ' damage scale was used and evaluation was done in a blinded way. Grou p comparisons were done using the Mann-Whitney U-test for significance between the control and hypothermic groups. Immediate hypothermia aft er the third ischemic insult produced a significant protection in the CTX (P < 0.05), hippocampus (CAI and CA4, P < 0.01), STR (P < 0.001), SNr (P < 0.01), MGN (P < 0.01) and THL (P < 0.01). Cooling at 0.5 and 1 h after the third insult produced no protection when compared to isc hemic control. The window of opportunity with hypothermia is narrow in repetitive ischemia. To be effective, therapy must be initiated as so on as possible after ischemic insults.