TDN345

Male Mongolian gerbils (50-70 g body weight) are anesthetized lightly by ether inhalation. A 1-2 cm midline throat incision provided access to both carotid arteries, which are clamped with microaneurysm clamps immediately after recovery from anesthesia. Sixty minutes before occlusion, TDN-345 (0.3 or 1.0 mg/kg suspended in a 5% gum arabic solution or 0.1 or 0.3 mg/kg with 1% NaHCO3 suspended in a 5% gum arabic solution) or vehicle is administered orally. After 15 min of bilateral carotid artery occlusion, the clamps are removed. Ninety minutes after reperfusion, TDN-345 or vehicle is again administered orally. The body temperature is maintained at 37°C during the experimental period using a heating pad. The experiments are performed in nine to 15 animals in each group. Animal survival is observed 8 h and 7 days after reperfusion, and neurological signs are evaluated according to the scoring system as an ischemic neurological score for 5 h after the ischemic insult from an area under the time-neurological deficit score curve (AUC_{reperfusion (0-300 min)}) (hair roughed up or tremor, obtunded, paucity of move, 1; ptosis, seizure, 2; head cocked, eyes fixed open, splayed out hind limbs, extreme rotation, circling behavior, rolling seizure, 3; coma, 6; death, 34). Nine to 15 animals are used in each experimental group.

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