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Protective Effects of Valproic Acid Against Hypoxic-Ischemic Brain Injury in Neonatal Rats

Department of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey, nimetkabakus{at}yahoo.com.

Ilknur Ay, MD

Department of Pharmacology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Sabiha Aysun, MD

Department of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Figen Söylemezoglu, MD

Department of Neuropathology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Ayhan Özcan, MD

Department of Pathology, Gülhane Military Medical Academy, Ankara, Turkey

Bulent Celasun, MD

Department of Pathology, Gülhane Military Medical Academy, Ankara, Turkey

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 1 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. (J Child Neurol 2005;20:582—587).

Journal of Child Neurology, Vol. 20, No. 7, 582-587 (2005)
DOI: 10.1177/08830738050200070801


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