血管再通基础上神经保护的根本在于更有效的保护缺血半暗带组织，但保护机制和临床转化前景尚不明确。近期研究发现，受损神经元可以释放细胞因子、趋化因子等“help-me”信号而实现自我保护，这种内源性保护方式可能是干预的新靶点。我们前期成功制备恒河猴血栓-溶栓脑卒中模型，还发现血管再通基础上低温治疗通过降低凋亡、抑制炎症反应等方式对大鼠局部脑缺血模型具有保护作用。但该方法是否通过“help-me”信号介导，临床转化前景尚需更高级动物模型评估。本课题依托大鼠和恒河猴模型，拟采用MRI灌注成像方法量化再通基础上低温治疗对缺血半暗带的保护作用；采用蛋白芯片等方法从半暗带组织中发现1-2种新的“help-me”信号，经体外细胞共培养、转基因动物模型等方法验证；通过神经功能评分、多模态MRI成像等方法，在恒河猴模型上评估再通基础上低温治疗的神经保护作用，为脑卒中低温治疗提供直接证据。

Neuroprotection to prevent infarct progression as a potential treatment for acute ischemic stroke should be given a special attention in the reperfusion Era. The main purpose is to preserve penumbra, however, potential mechanism and promise is still not clear. Injured neurons could send “help-me” signals, such as cytokines, chemokines, even mitochondria, to attain helps from surrounding glial and vascular compartments. These signals may be new targets for treatments. Therapeutic hypothermia after successful recanalization is observed to have neuroprotective effects in rat MCAO models, including reduced apoptosis and inflammations. We also develop thrombus-thrombolysis stroke models in rhesus monkeys. Based on our previous observations, we make a hypothesis that therapeutic hypothermia after successful recanalization will have translational values in stroke patients. Penumbra tissue could be preserved following hypothermic therapy based on MRI images in rat and rhesus monkey models. Neuroprotection will be proved in rhesus models according to images, neurologic scores and behavior tests. Then, “help-me” signals will be screened based on penumbra tissues of rat and rhesus monkey models. “help-me” signals, will be confirmed according to in vitro cell cultures. The translational evidence will be collected based on data from animal models, MRI images and cell cultures.