Protective effects of valproic acid against hypoxic-ischemic brain injury in neonatal rats

Kabakus N., Ay I., Aysun S., Soylemezoglu F., Ozcan A., Celasun B.

JOURNAL OF CHILD NEUROLOGY, vol.20, no.7, pp.582-587, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 7
  • Publication Date: 2005
  • Doi Number: 10.1177/08830738050200070801
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.582-587
  • Hacettepe University Affiliated: No


Although controversial, protective and therapeutic effects of valproic acid in various types of cellular injury suggest a potential role for this agent in hypoxic-ischemic brain injury. We therefore investigated the effects of valproic acid in an experimental model of neonatal hypoxic-ischemic brain injury. To examine the effect of valproic acid in this condition, hypoxic-ischemic brain injury was induced in 7-day-old rat pups by ligation of the right common carotid and then the pups were exposed to I hour of hypoxia in 8% oxygen. Low (200 mg/kg/day) and high (400 mg/kg/day) doses of valproic acid were administered in a 5-day regimen. Neuropathologic evaluation was performed using the hippocampus, cerebral cortex, and basal ganglia in the coronal plane. The 5-day regimen of valproic acid administration resulted in some protective and therapeutic effects on the brain damage and neuronal apoptosis in both hemispheres in a dose-dependent manner. Administration of valproic acid also decreased the percentage of apoptotic neurons in the contralateral hemisphere (P <.05). These results suggest that valproic acid can have therapeutic and protective effects in hypoxic-ischemic brain injury.