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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Apr;114(8):1631–1635. doi: 10.1111/j.1476-5381.1995.tb14950.x

The effect of chlormethiazole on neuronal damage in a model of transient focal ischaemia.

S G Sydserff 1, A J Cross 1, K J West 1, A R Green 1
PMCID: PMC1510402  PMID: 7599933

Abstract

1. The effect of chlormethiazole has been studied in a transient middle cerebral artery (MCA) occlusion model of cerebral ischaemia in the rat. The MCA was occluded for 1 h by use of an intraluminal suture technique, with reperfusion for 24 h following removal of the occluding filament. Neuronal damage was determined by measurement of the area of necrosis following Cresyl Violet staining of sections taken through the ischaemic region. 2. In the initial experiment, occlusion of the MCA produced a large volume of ischaemic damage in both cortex and striatum, characterized by necrosis and pyknosis (total volume of damage, 287 +/- 13 mm3, n = 9). Rats injected with chlormethiazole (1000 mumol kg-1, i.p.) 60 min before occlusion had a reduced volume of damage in both regions (104 +/- 11 mm3; n = 9; P < 0.001). 3. In a subsequent study systemic physiological parameters (heart rate, blood pressure, blood pH, blood gases and rectal temperature) were measured throughout the ischaemic period. 4. Chlormethiazole (1000 mumol kg-1) pretreatment produced little change in systemic physiology and the neuroprotective effect of the drug when given 60 min prior to the MCA occlusion was confirmed. Chlormethiazole was also neuroprotective when given 10 min following the start of reperfusion (control group: 244 +/- 52 mm3, n = 10; chlormethiazole pretreatment group: 102 +/- 23 mm3, n = 10; P < 0.001; chlormethiazole post-ischaemia group: 122 +/- 16 mm3; P < 0.001, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

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