Protective effects of topiramate against hyperoxic brain injury in the developing brain

Neuropediatrics. 2009 Feb;40(1):22-7. doi: 10.1055/s-0029-1224101. Epub 2009 Jul 28.

Abstract

Recent studies have shown that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. Besides its antiepileptic effects, topiramate exerts neuroprotective effects in animal models of stroke, hypoxia ischemia, excitotoxic insults, and status epilepticus. In the present study, we investigated the effects of topiramate against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+phosphate buffered saline treated group and hyperoxia+topiramate treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in plexiglas chambers in which the oxygen concentration was monitored twice daily from birth until postnatal day five. The hyperoxia+topiramate group received an intraperitoneal injection of topiramate at a dose of 80 mg/kg/day. At postnatal day 5, all animals were killed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that topiramate significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus. Topiramate may offer a therapeutic potential for neuroprotection under conditions of hyperoxic brain injury.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Brain Injuries / drug therapy*
  • Brain Injuries / etiology
  • Brain Injuries / pathology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • DNA / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Fructose / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / growth & development
  • Hippocampus / pathology
  • Histones / metabolism
  • Hyperoxia / complications
  • In Situ Nick-End Labeling / methods
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Parietal Lobe / drug effects
  • Parietal Lobe / growth & development
  • Parietal Lobe / pathology
  • Rats
  • Rats, Wistar
  • Topiramate

Substances

  • Histones
  • Neuroprotective Agents
  • Topiramate
  • Fructose
  • DNA