Transient forebrain ischemia under hyperthermic condition accelerates memory impairment and neuronal death inthegerbil hippocampus by increasing NMDAR1 expression.

Abstract

Altered expression levels of N-methyl-D-aspartate receptor (NMDAR), a ligand-gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI-induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post-tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post-tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI-induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.