Comparison of neuronal death and expression of TNF­α and MCT4 in the gerbil hippocampal CA1 region induced by ischemia/reperfusion under hyperthermia to those under normothermia.

ABSTRACT

Monocarboxylate transporter 4 (MCT4) is a high­capacity lactate transporter in cells and the alteration in MCT4 expression harms cellular survival. The present study investigated whether hypothermia affects tumor necrosis factor­α (TNF­α) and MCT4 immunoreactivity in the subfield cornu ammonis 1 (CA1) following cerebral ischemia/reperfusion (IR) in gerbils. Hypothermia was induced for 30 min before and during ischemia. It was found that IR­induced death of pyramidal neurons was markedly augmented and occurred faster under hyperthermia than under normothermia. TNF­α immunoreactivity in the pyramidal cells started to increase at 3 h after IR and peaked at 1 day after IR under normothermia. However, in hyperthermic control and sham operated gerbils, TNF­α immunoreactivity was significantly increased compared with the normothermic gerbils, and IR under hyperthermia caused a more rapid and significant increase in TNF­α immunoreactivity in pyramidal neurons than under normothermia. In addition, in the normothermic gerbils, MCT4 immunoreactivity began to decrease in pyramidal neurons from 3 h after IR and markedly increased at 1 and 2 days after IR. On the other hand, MCT4 immunoreactivity in pyramidal neurons of the hyperthermic gerbils was significantly increased from 3 h after IR, maintained until 1 day after IR and markedly decreased at 2 days after IR. These results indicate that acceleration of IR­induced neuronal death under hyperthermia might be closely associated with early alteration of TNF­α and MCT4 protein expression in the gerbil hippocampus after IR.