Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury.
Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury.
复制标题
亚低温与神经保护剂的结合在氧糖剥夺和复氧介导的神经元损伤期间具有更大的神经保护作用
DOI：
10.1038/srep07091
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发表时间：
2014-11-18
影响因子：
4.6
通讯作者：
Pan SY
中科院分区：
文献类型：
--
作者：
Gao XY;Huang JO;Hu YF;Gu Y;Zhu SZ;Huang KB;Chen JY;Pan SY
神经保护剂的联合治疗可能会提高低温在缺血性卒中中保护神经元的治疗效果。本研究旨在寻找有前途的药物，以加强亚低温（MH）的神经保护作用。根据不同靶点筛选出26种候选药物。将原代培养的皮层神经元暴露于氧-葡萄糖剥夺和再给氧（OGD/R）以诱导神经元损伤，随后进行单一处理（药物或MH）或药物和MH的组合。结果表明，与单独用药相比，MH与脑源性神经营养因子、格列本脲、地佐环平、人尿激肽原酶或脑红蛋白联合用药可提高神经细胞存活率。后三种药物联合用药时细胞凋亡率也较低。此外，这三种药物和MH的联合治疗降低了活性氧（ROS）水平和细胞内钙积累，以及稳定线粒体膜电位（MMP），表明联合神经保护作用可能是通过抑制线粒体凋亡途径。总之，该研究表明，低温和某些神经保护剂的联合治疗提供了更好的保护，防止OGD/R诱导的神经元损伤。
Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury.