Initiation time of post-ischemic hypothermia on the therapeutic effect in cerebral ischemic injury

Abstract

Objective: To study the efficacy of mild brain hypothermia beginning at different time intervals on cerebral ischemic injury.Methods: Male Sprague–Dawley rats were divided into sham-operated group, normothermia (37–38°C) and mild hypothermia (31–32°C) ischemia groups. The last group was subdivided into four groups: 240 minute hypothermia, 30 minute normothermia plus 210 minute hypothermia, 60 minute normothermia plus 180 minute hypothermia, and 90 minute normothermia plus 150 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20 minutes and mild hypothermia was applied after 20 minutes of ischemia. Brain tissue was collected following 20 minute cerebral ischemia and 240 minute reperfusion, and used to measure the levels of malondialdehyde (MDA), lactate, water content and the amounts of electrolytes, such as sodium (Na+), potassium (K+) and calcium (Ca++).Results: Mild hypothermia beginning at 0–60 minutes decreased the levels of malondialdehyde and lactate (p<0.05 or p<0.01), decreased water content, Na+ and Ca++, and increased the amount of K+ (p<0.05 or p<0.01) in ischemic tissue, except the amounts of Na+, K+ and Ca++ in mild hypothermia beginning at 60 minute ischemia group (p>0.05). Mild hypothermia beginning at 90 minutes had little effect on the levels of targeted molecules, water content and amounts of electrolytes of Na+, K+ and Ca++ in ischemic tissue (p>0.05).Discussion: Post-ischemic mild brain hypothermia can decrease the accumulation of lactate and lipid peroxidation in ischemic tissue, and delay the development of brain edema following ischemic reperfusion. The best neuroprotection of mild hypothermia to attenuate ischemic injury was begun within 60 minutes.