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, cilt.20, sa.7, ss.582-587, 2005 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 20 Konu: 7
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1177/08830738050200070801
  • Sayfa Sayıları: ss.582-587


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.