Preventing hyperthermia decreases brain damage following neonatal hypoxic-ischemic seizures

Jerome Y. Yager, Edward A. Armstrong, Cleo Jaharus, Deborah M. Saucier, Elaine C. Wirrell

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Neonatal seizures are the most common manifestation of underlying cerebral dysfunction. Hypoxic-ischemic encephalopathy is the cause of seizures in 40-60% of newborns. Previous work from our laboratory demonstrates that seizures associated with a hypoxic-ischemic insult results in aggravation of neuronal cell death, specifically within the hippocampus. The latter occurs in the setting of spontaneously occurring hyperthermia of 1.5°C. The purpose of this study was to determine whether preventing the onset of seizure induced hyperthermia would be neuroprotective. Three groups of 10-day old rat pups received unilateral hypoxic-ischemic insults for 30 min followed by KA-induced seizures. Hyperthermia was prevented by lowering the environmental temperature ("relative hypothermia") to 29°C such that the seizuring rat pups were normothermic. In one group, the prevention of hyperthermia occurred immediately following hypoxia-ischemia, whereas in the other group it occurred at the onset of seizures. The third group of rat pups (controls) remained at their nesting temperature and therefore became hyperthermic during seizures. Early (3 days) and late (20 days) neuropathology was assessed. Rat pups in whom hyperthermia was prevented during seizures displayed a significant reduction in brain damage compared to controls (p<0.05). Assessment of hippocampal brain damage also showed a significant improvement in neuronal necrosis at 20 days of recovery compared to 3 days of recovery (p<0.05). The results indicate that preventing spontaneous hyperthermia in this model of hypoxic-ischemic seizures in the newborn is neuroprotective.

Original languageEnglish (US)
Pages (from-to)48-57
Number of pages10
JournalBrain Research
Volume1011
Issue number1
DOIs
StatePublished - Jun 11 2004

Keywords

  • Brain
  • Damage
  • Disorders of the nervous system
  • Epilepsy: human studies and animal models
  • Hyperthermia
  • Hypoxia-ischemia
  • Neonatal
  • Seizures

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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