机构：[1]Nanfang Hospital, Southern Medical University, Guangzhou 510515, China[2]The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000,China[3]Department of Anesthesia, Guangdong Provincial Hospital of ChineseMedicine, Guangzhou 510120, China
Background Remote ischemic preconditioning (RIPC) initiates endogenous protective pathways in the brain from a distance and represents a new, promising paradigm in neuroprotection against cerebral ischemia-reperfusion (I/R) injury. However, the underlying mechanism of RIPC-mediated cerebral ischemia tolerance is complicated and not well understood. We reported previously that preactivation of Notch1 mediated the neuroprotective effects of cerebral ischemic preconditioning in rats subjected to cerebral I/R injury. The present study seeks to further explore the role of crosstalk between the Notch1 and NF-kappa B signaling pathways in the process of RIPC-induced neuroprotection. Methods Middle cerebral artery occlusion and reperfusion (MCAO/R) in adult male rats and oxygen-glucose deprivation and reoxygenation (OGD/R) in primary hippocampal neurons were used as models of I/R injury in vivo and in vitro, respectively. RIPC was induced by a 3-day procedure with 4 cycles of 5 min of left hind limb ischemia followed by 5 min of reperfusion each day before MCAO/R. Intracerebroventricular DAPT injection and sh-Notch1 lentivirus interference were used to inhibit the Notch1 signaling pathway in vivo and in vitro, respectively. After 24 h of reperfusion, neurological deficit scores, infarct volume, neuronal apoptosis, and cell viability were assessed. The protein expression levels of NICD, Hes1, Phospho-IKK alpha/beta (p-IKK alpha/beta), Phospho-NF-kappa B p65 (p-NF-kappa B p65), Bcl-2, and Bax were assessed by Western blotting. Results RIPC significantly improved neurological scores and reduced infarct volume and neuronal apoptosis in rats subjected to I/R injury. OGD preconditioning significantly reduced neuronal apoptosis and improved cell viability after I/R injury on days 3 and 7 after OGD/R. However, the neuroprotective effect was reversed by DAPT in vivo and attenuated by Notch1-RNAi in vitro. RIPC significantly upregulated the expression of proteins related to the Notch1 and NF-kappa B pathways. NF-kappa B signaling pathway activity was suppressed by a Notch1 signaling pathway inhibitor and Notch1-RNAi. Conclusions The neuroprotective effect of RIPC against cerebral I/R injury was associated with preactivation of the Notch1 and NF-kappa B pathways in neurons. The NF-kappa B pathway is a downstream target of the Notch1 pathway in RIPC and helps protect focal cerebral I/R injury.
基金：
Science and Technology Research Project Fund of the Jiangxi Provincial Ministry of Education [GJJ160967]
第一作者机构：[1]Nanfang Hospital, Southern Medical University, Guangzhou 510515, China[2]The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000,China
通讯作者：
推荐引用方式(GB/T 7714)：
Liang Weidong,Lin Chunshui,Yuan Liuqing,et al.Preactivation of Notch1 in remote ischemic preconditioning reduces cerebral ischemia-reperfusion injury through crosstalk with the NF-kappa B pathway[J].JOURNAL OF NEUROINFLAMMATION.2019,16(1):doi:10.1186/s12974-019-1570-9.
APA：
Liang, Weidong,Lin, Chunshui,Yuan, Liuqing,Chen, Li,Guo, Peipei...&Zhang, Xin.(2019).Preactivation of Notch1 in remote ischemic preconditioning reduces cerebral ischemia-reperfusion injury through crosstalk with the NF-kappa B pathway.JOURNAL OF NEUROINFLAMMATION,16,(1)
MLA：
Liang, Weidong,et al."Preactivation of Notch1 in remote ischemic preconditioning reduces cerebral ischemia-reperfusion injury through crosstalk with the NF-kappa B pathway".JOURNAL OF NEUROINFLAMMATION 16..1(2019)
医学