Zhou You-Dong, Cai Li
Department of Neurosurgery, Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science, Xiangyang, Hubei, China.
J Stroke Cerebrovasc Dis. 2019 Jan;28(1):125-132. doi: 10.1016/j.jstrokecerebrovasdis.2018.09.026. Epub 2018 Oct 16.
Inhibition of calpain activity provides neuroprotection in multiple central nervous system injury, but the role and mechanism of calpain in subarachnoid hemorrhage (SAH) remain unclear. This study was undertaken to determine the effects of inhibition of calpain on neurological deficit and neuronal apoptosis following experimental SAH.
The endovascular perforation model of SAH was produced in male Sprague-Dawley rats. Rats were administered calpeptin 50 μg, intracerebroventricular injection, 30 minutes before induction of SAH. After 72 hours, the method of Evans blue dye extravasation and wet/dry method were used for determination of blood-brain barrier permeability and brain edema, Western blot analysis and immunohistological staining were used to evaluate neuronal apoptosis.
The intracellular Ca level and calpain activity was significantly elevated in basal cortex after SAH. Calpain inhibitor calpeptin reduces brain water content and Evans blue dye extravasation, improves neurobehavioral deficits after SAH. Importantly, calpeptin treatment significantly reduces activation of caspase-3, caspase-9, caspase-12 and poly ADP ribose polymerase and the number of apoptotic neurons in basal cortex after SAH.
The present study suggested that calpeptin is neuroprotective in early brain injury after SAH through antiapoptotic effect.
抑制钙蛋白酶活性可在多种中枢神经系统损伤中提供神经保护作用，但钙蛋白酶在蛛网膜下腔出血（SAH）中的作用及机制仍不清楚。本研究旨在确定抑制钙蛋白酶对实验性SAH后神经功能缺损和神经元凋亡的影响。
在雄性Sprague-Dawley大鼠中建立SAH的血管内穿刺模型。在诱导SAH前30分钟，通过脑室内注射给予大鼠50μg钙蛋白酶抑制剂。72小时后，采用伊文思蓝染料外渗法和干湿法测定血脑屏障通透性和脑水肿，采用蛋白质免疫印迹分析和免疫组织化学染色评估神经元凋亡。
SAH后基底皮质细胞内Ca水平和钙蛋白酶活性显著升高。钙蛋白酶抑制剂钙蛋白酶抑制剂可降低脑含水量和伊文思蓝染料外渗，改善SAH后的神经行为缺损。重要的是，钙蛋白酶抑制剂处理可显著降低SAH后基底皮质中caspase-3、caspase-9、caspase-12和聚ADP核糖聚合酶的激活以及凋亡神经元的数量。
本研究表明，钙蛋白酶抑制剂通过抗凋亡作用对SAH后的早期脑损伤具有神经保护作用。
