Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia
Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia
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DOI：
10.1016/s0304-3940(98)00266-3
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发表时间：
1998-05-08
影响因子：
2.5
通讯作者：
Shuaib, A
中科院分区：
文献类型：
--
作者：
Li, PA;Howlett, W;Shuaib, A
新开发的钙蛋白酶抑制剂MDL 28170在全身给药后穿透血脑屏障并抑制脑半胱氨酸蛋白酶活性。开始该实验以确定钙蛋白酶抑制剂MDL 28170是否可以通过这些作用减少沙鼠全脑缺血动物模型中的神经元损伤。钙蛋白酶抑制剂MDL 28170（50 mg/kg）在全脑缺血5 min后再循环0.5和3 h时开始给药。经受局部缺血但未处理或用媒介物处理的动物用作对照。通过光学显微镜对手术后7天处死的沙鼠的石蜡包埋脑切片进行评价。结果表明，钙蛋白酶抑制剂，MDL 28170，保护皮质神经元损伤，即使治疗延迟到3小时后再灌注。然而，这种药物的神经保护作用在海马CA 1区不太明显。结果表明钙蛋白酶介导的蛋白水解在缺血性神经元死亡中起重要作用，然而，可能存在细胞内钙浓度增加导致神经元死亡的其他机制。(C)1998爱思唯尔科学爱尔兰有限公司
The newly-developed calpain inhibitor, MDL 28170 penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. This experiment was initiated to determine if the calpain inhibitor, MDL 28170 could, by these actions, reduce neuronal damage in an animal model of global cerebral ischemia in the gerbil. The calpain inhibitor, MDL 28170 (50 mg/kg), was initiated at 0.5 and 3 h of recirculation following 5min of global ischemia. Animals subjected to ischemia but without treatment or with vehicle treatment served as controls. Evaluation by light microscopy was carried out on paraffin-embedded brain sections of gerbils which were sacrificed 7 days post-operatively. The results show that the calpain inhibitor, MDL 28170, protects against cortical neuronal damage even if the treatment is delayed until 3 h after reperfusion. However, the neuroprotective effect of this agent is less pronounced in the hippocampal CA1 sector. The results suggest that calpain-mediated proteolysis plays an important role in neuronal death due to ischemia, However, additional mechanisms by which an increased intracellular calcium concentration leads to neuronal death may exist. (C) 1998 Elsevier Science Ireland Ltd.