Peng Cheng, Wang Li-Ping, Tao Xia, Dong Xiao-Hui, Xu Chun-Fang, Jiang Yu, Liu Chun-Long, Ma Hui-Fang, Zhang Chuan, Chen Alex F, Xie He-Hui
School of Public Health and Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pharmacy, Zhongshan Hospital, Qingpu branch, Fudan University, Shanghai, China.
Cell Physiol Biochem. 2018;45(1):175-191. doi: 10.1159/000486356. Epub 2018 Jan 15.
BACKGROUND/AIMS: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury.
After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated.
Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice.
Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke.
背景/目的：长期冷暴露可能增加能量消耗，有助于对抗肥胖，而肥胖是心脑血管疾病的重要危险因素。本研究旨在评估缺血发作前进行预防性冷适应是否可能是预防脑缺血损伤的一个有前景的选择。
经过14天的冷适应期后，对年轻和老年小鼠进行永久性脑缺血，并进行组织学分析和行为测试。分离小鼠内皮祖细胞（EPCs），测定其功能和数量，并研究EPC移植对脑缺血损伤的影响。
缺血发作前进行预防性冷适应可增强EPC功能，促进缺血性脑的血管生成，保护脑缺血损伤，并改善年轻小鼠的长期中风结局。此外，与对照小鼠来源的EPC相比，冷暴露小鼠来源的移植EPC具有更强的减轻脑缺血损伤和促进局部血管生成的能力，且供体动物的EPC可整合到受体缺血性鼠脑内。此外，移植的EPC可能对脑缺血损伤发挥旁分泌作用，预防性冷适应可改善这种作用。而且，预防性冷适应还可增强老年小鼠的EPC功能，促进局部血管生成，并保护其免受脑缺血损伤。
缺血发作前进行预防性冷适应至少部分通过促进EPC的修复功能改善了小鼠的长期中风结局。我们的研究结果表明，经常冷暴露的可变室内环境可能使中风高危个体受益。
