Mild hypothermia pretreatment protects against pilocarpine-induced status epilepticus and neuronalapoptosis in immature rats

Abstract

Hypothermia has been shown to have neuroprotective effects in various models of neurological damage. However, its effects on pediatric status epilepticus (SE) are relatively unknown. In order to understand the effects of hypothermia on pediatric SE, we conducted experiments to determine the neuroprotective effects of mild hypothermic pretreatment in a model of pediatric SE. Juvenile (21-day-old) rats were subjected to mild hypothermic or normothermic conditions prior to intraperitoneal injections of pilocarpine. We analyzed the seizure response of these animals via electroencephalogram and conducted ex-vivo analysis for apoptotic cells in the hippocampus via a TUNEL assay. We found that mild hypothermia increased both seizure latency and time to SE onset. It also reduced the overall average spike frequency and spike area compared to normothermia controls. Furthermore, the number of apoptotic cells was reduced in the hippocampus. In conclusion, these data indicate that mild hypothermia reduces both seizure activity and neurotoxicity in a pilocarpine model of pediatric SE. This expands previous findings examining the neuroprotective effect of hypothermia by showing neuroprotection in a pediatric model of SE. We believe these findings will help researchers find better preventative treatments for pediatric SE in the future.

Potential mechanisms and clinical applications of mild hypothermia and electroconvulsive therapy on refractory status epilepticus

“…Subsequent studies have shown that protection of the brain during early seizures has an inhibitory effect on seizures. Yu et al [31] found that hypothermia pre-treatment reduced hippocampal neuronal apoptosis in a pilocarpine-induced rat model of SE. Nitric oxide (NO) is neurotoxic [32], and it interferes with neuronal apoptosis by intervention of glycolysis and the pentose phosphate pathway in the regulation of glucose consumption [33].…”

Therapeutic brain hypothermia, its mechanisms of action, and its prospects as a treatment for epilepsy

“…Pilocarpine‐induced SE in rat pups has been used as a model of pediatric SE. Animals kept mildly hypothermic before pilocarpine injection show longer seizure latency, longer SE latency, lower spike frequency, smaller spike area, and less hippocampal apoptosis than controls (Yu et al., ). However, timing of intervention was critical in preventing neural damage and seizures in a group of near‐term fetal sheep.…”

Hypothermia for pediatric refractory status epilepticus

“…In rats with seizures induced by potassium channel antagonists (Yang & Rothman, ) or by fluid percussive injury (D'Ambrosio et al., ), focal cortical cooling significantly reduced seizure frequency. In rats injected with pilocarpine, hypothermia pretreatment reduced neuronal apoptosis and increased latency to SE onset (Maeda et al., ; Yu et al., ). Hypothermia also decreased brain edema and seizure frequency in rats with kainic acid–induced SE (Wang et al., ).…”