Zonisamide reduces hypoxic-ischemic brain damage in neonatal rats irrespective of its anticonvulsive effect.
The neuroprotective effect of a novel anticonvulsant, zonisamide, was investigated in neonatal rats with hypoxic-ischemic brain damage. Rats underwent left carotid ligation followed by hypoxic exposure (8% O2) for 2.5 h. When zonisamide (75 mg/kg) was administered i.p. 1 h before hypoxia, it reduced the cortical infarction volume to 6 +/- 5% (mean +/- S.E.M.) from 68 +/- 7% in vehicle-treated controls and the striatal volume to 8 +/- 4% from 78 +/- 7%. Zonisamide also reduced neuronal necrosis in 5 hippocampal regions (the dentate gyrus, CA4, CA3, CA1, and the subiculum). The plasma zonisamide concentration before and after hypoxia was 47.9 +/- 2.0 microgram/ml and 42.3 +/- 3.9 microgram/ml, respectively. Epidural electrodes were implanted in 6 pups one day before hypoxia-ischemia. Electroencephalograms were recorded during hypoxia-ischemia in rats given zonisamide or vehicle before the insult. The intensity of seizure activities was similar in the zonisamide-treated pups and the vehicle-treated controls. These findings demonstrate that zonisamide reduces neonatal hypoxic-ischemic brain damage and that this protective effect does not depend on its anticonvulsant action.
Hayakawa
T
T
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Higuchi
Y
Y
Nigami
H
H
Hattori
H
H
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000097:blood / Q000627:therapeutic use*; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide