Effect of mild hypothermia on glutamate receptor expression after status epilepticus

Abstract

Hypothermia has been shown to have neuroprotective effects in various models of neurological damage. However, its therapeutic effect on pediatric status epilepticus (SE) is still unknown. We conducted a study to investigate whether hypothermia can have an adjuvant effect on pilocarpine-induced status epilepticus in immature rats when combined with diazepam treatment. Pilocarpine-induced status epilepticus was maintained for either 30 min or 60 min, which was followed by injection with diazepam (10mg/kg body weight) and/or treatment with mild hypothermia (core temperature to 33°C). We found that the spike-wave amplitude and frequency after SE during treatment with diazepam and hypothermia was significantly lower than treatment with diazepam alone. Mild hypothermia significantly reduced the number of cells undergoing necrosis and apoptosis. In addition, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor subunit GluR1 was shown to be up-regulated by SE, while GluR2 was shown to be down-regulated. However, after combination therapy with diazepam and mild hypothermia for 8h, the expression of GluR1 was decreased and GluR2 was increased relative to the levels of diazepam alone treated juveniles. We also found that the expression of mGluR-1a was also decreased relative to diazepam alone. These findings suggest that mild hypothermia might further protect against pilocarpine-induced status epilepticus in immature rats by regulating glutamate receptor expression. This study was conducted using a pediatric model of SE so as to gain a better understanding of the role of hypothermia in the developing brain.