THE NEUROPROTECTIVE EFFECT OF CHLORMETHIAZOLE ON ISCHEMIC NEURONAL DAMAGE FOLLOWING PERMANENT MIDDLE CEREBRAL-ARTERY ISCHEMIA IN THE RAT

The ability of chloremethiazole to protect against ischaemic cell dama ge in a rat model of permanent focal ischaemia has been examined. Chlo rmethiazole (1 mmol/kg) was administered intraperitoneally either 1 or 3 h after occlusion of the middle cerebral artery with an intralumina l filament. Twenty four hours after the start of occlusion there was h istological evidence for ischaemic damage in both cortex and striatum. The volume of ischaemic damage in control (saline injected) animals w as 310 +/- 25 mm(3) (mean +/- SEM; n = 6). Chlormethiazole administere d 1 h after occlusion reduced this damage by 58% (128 +/- 40 mm(3); n = 6; P < 0.01), protection being observed in both brain regions. The d rug was ineffective when given 3 h after occlusion (304 +/- 25 mm(3); n = 5). Chlormethiazole had no effect on body temperature, mean arteri al blood pressure, blood FH, pO(2) or pCO(2), but did induce mild brad ycardia. Chlormethiazole therefore appears to be an effective neuropro tective agent in this model of permanent ischaemia, complementing prev ious data on the efficacy of this drug in other focal and global model s of cerebral ischaemia. (C) 1995 Academic Press Limited