RESUMO
OBJECTIVE: To investigate the effect of intraischemic mild hypothermia on the protein levels of interleukin (IL)-1beta and monocyte chemoattractant protein (MCP)-1 in the ischemic core of rat cortex after transient focal cerebralischemia. METHODS: Eighty male Wistar rats were randomly divided into normothermic (37 degrees C) and mild hypothermic (32 - 33 degrees C) groups. The normothermic group was redivided into six subgroups of 8 rats: sham operation, ischemia for 2 hours without reperfusion, and reperfusion for 6 hours, 16 hours, 24 hours, and 48 hours respectively after ischemia; and the mild hypothermic group was redivided into 4 group with 8 rats: reperfusion for 6, 16, 24, and 48 hours. The rats except those in the sham operation subgroup were subjected to right middle cerebral artery occlusion by insertion a specially prepared nylon filament for two hours. Ice bag was used to lower the brain temperature and anal temperature soon after ischemia to 32.0 - 33.0 degrees C within 10 minutes in the mild hypothermic subgroups. The brain and anal temperature remained at 37.0 - 37.5 degrees C in all normothermic subgroups. Then the rats were killed 0, 6, 16, 24 and 48 hours after reperfusion respectively and their brains were taken out to examine the size of brain infarct by 2,3,5-triphenyltetrazolium chloride (TTC) staining reaction. The protein levels of IL-1beta and MCP-1 in the cortical ischemic core were measured by ELISA. RESULTS: No significant change of IL-1beta protein level was found in the cortical ischemic cores at any time point after reperfusion among the normothermic subgroups. The IL-1beta protein levels at different time points were not significantly different between the intraischemic mild hypothermia subgroups and the normothermic subgroups (all P > 0.05). The MCP-1 protein level in the cortical ischemic cores of the normothermic subgroups began to increase since the 6th hour afer reperfusion (22.5 +/- 8.7 ng x g tissue(-1), 17 times that in the sham operation samples, P < 0.05), peaked in 48 hours (110.9 +/- 47.0 ng x g tissue(-1), 83.7 times that in the sham operation sample, P < 0.001). The protein level of MCP-1 in the mild hypothermic subgroups was 8.7 +/- 7.6 ng x g tissue(-1) 6 h after reperfusion (P < 0.005 in comparison with those in sham operation subgroup and ischemia subgroup) and was 56.0 +/- 40.3 ng x g tissue(-1), 48 hours after reperfusion (P < 0.05) incomparison with those in the normothermic subgroups). The sizes of cortical infarct at different time points in the mild hypothermic subgroups were significantly smaller than those in the normothermic subgroups (P < 0.05). CONCLUSION: Mild hypothermia reduces the level of MCP-1 in the cortex after cerebral ischemia/reperfusion which may be one of the important mechanisms of the neuroprotective effects of mild hypothermia.
