Snape M F, Baldwin H A, Cross A J, Green A R
Astra Neuroscience Research Unit, London, U.K.
Neuroscience. 1993 Apr;53(3):837-44. doi: 10.1016/0306-4522(93)90628-s.
Focal ischaemia in the rat cerebral cortex was produced by means of a photochemically induced thrombosis of cerebral arteries. This was achieved by intravenous infusion of the photosensitive dye Rose Bengal and illumination of the skull with focused green light. Initial experiments justified the use of tetrazolium staining as an index of infarct damage. Using this technique it was demonstrated that chlormethiazole (200 mg/kg, i.p.) given 5 min post ischaemia markedly reduced the area of infarcted cortical tissue. A second experiment replicated this observation and showed that, in contrast, nimodipine (0.5 mg/kg, i.p.) given 5 min post infarct was without effect on infarct size. The pattern of Evans Blue extravasation indicated that the infarct developed over a 24-h period with the major damage occurring in the first 4.5 h. The spread of the infarct beyond the initial core of damage was decreased by an estimated value of almost 50% by injection of chlormethiazole (200 mg/kg, i.p.) 5 min after the light exposure. These data indicate that chlormethiazole is an effective drug in protecting against the effects of focal ischaemia in the rat and, taken with earlier observations that chlormethiazole protects against the effects of global ischaemia in the gerbil, suggest that the drug may be an effective treatment against the ischaemic cell death that can occur following a stroke or cardiac arrest.
通过光化学诱导脑动脉血栓形成，在大鼠大脑皮层产生局灶性缺血。这是通过静脉输注光敏染料孟加拉玫瑰红并用聚焦绿光照射颅骨来实现的。初步实验证明使用四氮唑染色作为梗死损伤的指标是合理的。使用该技术表明，缺血后5分钟腹腔注射氯美噻唑（200毫克/千克）可显著减少梗死皮层组织的面积。第二项实验重复了这一观察结果，并表明，相比之下，梗死5分钟后腹腔注射尼莫地平（0.5毫克/千克）对梗死面积没有影响。伊文思蓝外渗模式表明，梗死在24小时内发展，主要损伤发生在最初的4.5小时内。光暴露5分钟后注射氯美噻唑（200毫克/千克，腹腔注射），梗死超出初始损伤核心的范围估计减少了近50%。这些数据表明，氯美噻唑是一种有效药物，可保护大鼠免受局灶性缺血的影响，并且结合早期观察到氯美噻唑可保护沙鼠免受全脑缺血的影响，表明该药物可能是治疗中风或心脏骤停后可能发生的缺血性细胞死亡的有效方法。
