Zhang Shehong, Wang Yuyang, Li Dake, Wu Junfa, Si Wen, Wu Yi
Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Medicines (Basel). 2016 Jul 1;3(3):16. doi: 10.3390/medicines3030016.
Multiple cell death is involved in ischemic brain injury. Necroptosis, a recently reported cell death, may be the most suitable cell death mechanism in a subpopulation of neurons under ischemic injury. It reported that a small molecule, necrostatin-1 (Nec-1), has a potent inhibitory effect on necroptotic cell death in vivo and in vitro. The aim of the current study was to investigate the role of Nec-1 on cognitive function in chronic ischemic stroke mice induced by bilateral common carotid artery stenosis (BCAS). Here, 12-week-old C57BL/6 mice received intragastric administration with Nec-1 or vehicle for two weeks after stroke, and then, the effect and possible mechanism were determined. We demonstrated that inhibition of necroptosis prevented cognitive impairment and reduced inflammatory response in the ischemic brain injury mouse model. These data suggested that inhibition of necroptosis provided a potential therapeutic option for cognitive rehabilitation in chronic ischemic stroke.
多种细胞死亡参与缺血性脑损伤。坏死性凋亡是最近报道的一种细胞死亡方式，可能是缺血性损伤下神经元亚群中最合适的细胞死亡机制。据报道，一种小分子坏死性凋亡抑制剂-1（Nec-1）在体内和体外对坏死性凋亡细胞死亡具有强大的抑制作用。本研究的目的是探讨Nec-1对双侧颈总动脉狭窄（BCAS）诱导的慢性缺血性脑卒中小鼠认知功能的作用。在此，12周龄的C57BL/6小鼠在中风后接受Nec-1或赋形剂灌胃两周，然后确定其效果和可能的机制。我们证明，在缺血性脑损伤小鼠模型中，抑制坏死性凋亡可预防认知障碍并减少炎症反应。这些数据表明，抑制坏死性凋亡为慢性缺血性脑卒中的认知康复提供了一种潜在的治疗选择。
