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

Neuropathology. 2011 Apr;31(2):144-51. doi: 10.1111/j.1440-1789.2010.01155.x. Epub 2010 Sep 29.

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.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Convulsants / toxicity
  • Hypothermia, Induced*
  • In Situ Nick-End Labeling
  • Neurons / pathology*
  • Pilocarpine / toxicity
  • Rats
  • Rats, Wistar
  • Status Epilepticus / chemically induced
  • Status Epilepticus / pathology
  • Status Epilepticus / prevention & control*

Substances

  • Convulsants
  • Pilocarpine