Dantrolene enhances the protective effect of hypothermia on cerebral cortex neurons  

作　　者：Sui-yi Xu Feng-yun Hu Li-jie Ren Lei Chen Zhu-qing Zhou Xie-jun Zhang Wei-ping Li 

机构地区：[1]Postdoctoral Workstation, Zhongshan School of Medicine, Sun Yat-sen University [2]Department of Brain Center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People’s Hospital [3]Shenzhen University First Affiliated Hospital [4]Department of Neurology, Shanxi Provincial People’s Hospital, Shanxi Medical University

出　　处：《Neural Regeneration Research》2015年第8期1279-1285,共7页中国神经再生研究（英文版）

基　　金：supported by a grant from the Guangdong Science&Technology Plan Program in China,No.2014A020212043;the a grant from the Shenzhen Science&Technology Plan Program in China,No.JCYJ20140414170821242;the a grant from Shenzhen Collaborative Innovation Plan Program in China,No.GJHZ20120614154914623;a grant from the Science&Technology Project of Shanxi Health and Family Planning Commission in China,No.201201060

摘　　要：Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia（at 33°C）, or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia（at 33°C）, or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.

关 键 词：nerve regeneration ischemic stroke oxygen-glucose deprivation fluorescent probe neurons flow cytometry apoptosis calcium overload reactive oxygen neural regeneration 

分 类 号：R965[医药卫生—药理学]