Protective effects of valproic acid against hypoxic-ischemic brain injury in neonatal rats.
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.
Kabakus
Nimet
N
Department of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey. nimetkabakus@yahoo.com
Ay
Ilknur
I
Aysun
Sabiha
S
Söylemezoglu
Figen
F
Ozcan
Ayhan
A
Celasun
Bulent
B
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D000927:Anticonvulsants; D014635:Valproic Acid