Mechanism Study On Brain Protection Induced By Remote Ischemic Preconditioning: Evidence From Notch, S-100B And NSE

The stroke is an accident onset of the cerebral blood circulation disorders.Along the surgical techniques progress widely, more important organs may receivesurgery currently, incidence rate of perioperative stroke much increases. One of themost common reasons is brain ischemia-reperfusion injury. Especially, higherincidence of brain injury might occur as a range of brain disorders, e.g. stroke,encephalopathy and cognitive decline after cardiac surgery. While Stroke incidencerate is1%to3%, the incidence of cognitive dysfunction increased up to30%to65%after1month, and still remains20%to40%after5months. The CPB embolizationand brain hypoperfusion resulted from the cerebral ischemia/reperfusion injury isthought to be the main reason after brain injury.Recent evidence has shown that remote ischemic preconditioning can reducebrain and spinal cord damage resulted from ischemia-reperfusion. Because the remoteischemic preconditioning is a minimal invasive and easy to handle method, it can beeasily used for patients clinically and much better than classic ischemic preconditioning. Many studies have potently documented that Notch signalingfunctions actively in the nervous system and plays important roles in neuronaldifferentiation, maturation, regeneration, and even neurological diseases. Is Notchsignaling pathway involved in the brain protection induced by remote ischemicpreconditioning? What kind responses do neural cells have in remote ischemicpreconditioning? They are two interesting questions to be answered. Focused onthese questions, experiments have been performed to elucidate the preliminary basisof remote ischemic preconditioning-induced the brain protection mechanism.Part1: Remote ischemic preconditioning-induced brain protection andexpression changes of Notch signal moleculeObjective: To study expression changes of Notch signaling molecule in limb remoteischemic preconditioning-induced neuroprotection in rats. Methods: The middlecerebral artery occlusion (MCAO) rat model was prepared. Totally36male SD ratswere randomly divided into sham operation group (Sham), MCAO group, and limbremote ischemic preconditioning (RIPC)+MCAO group (n=10). The infarct size,neurological deficits score and immune-staining of NICD were observed at2h、24h、72h after reperfusion in brain striatum. Results:1. Infarct volume in RIPC group isless than that of MCAO group (P＜0.05).2. Neurological score in RIPC group wasalso significantly better than that of MCAO group (P＜0.05).3. immunofluorescence:NICD in RIPC group at2h、24h was significantly less than that of MCAO group.4.Western blot: the NICD expression in the RIPC group at2h、24h after reperfusionwere weak; the NICD expression in MCAOgroup at2h、24h after reperfusion werestronger than the RIPC group in the sametime (P＜0.05),but two groups was strongerthan the sham group (P＜0.05).5.Real-time PCR: mRNA expression of the receptornotch-1in the MCAO group increased at2h、24h after reperfusion, and higher than theRIPC group in the sametime (P＜0.05); The mRNA expression levels of target gene HES-1in the MCAO group at2h、24h after reperfusion increased gradually, werehigher than RIPC group in the sametime (P＜0.05); but at72h after reperfusion, theHES-1mRNA expression of the two groups was no significant difference.Conclusion: The limb distance pretreatment showed protective effect on cerebralischemia-reperfusion injury and decreasing of NICD expression, suggesting thatdown-regulation of Notch signaling might be involved in remote ischemicpreconditioning-induced brain protection.Part2: Protective effect of remote ischemic preconditioning on perioperativecerebral ischemia and reperfusion injury of patients with heart bypass surgeryObjective: To observe protective effect of limb remote ischemic preconditioning ofthe heart bypass surgery on perioperative cerebral ischemia-reperfusion injury.Methods: eighty patients undergoing elective heart valve replacement surgery beforeinduction of anesthesia were randomly divided into two groups: limb remote ischemicpreconditioning group and the control group with40patients of each. According tothe literature, limb remote ischemic preconditioning was carried out by usingpneumatic tourniquet on the implementation of the right upper limb ischemia3times5minutes5minutes reperfusion, inflatable pressure of200mmHg. The serumlevels of S-100B and neuron-specific enolase (NSE) were detected before induction ofanesthesia, CPB before surgery and at6,24,48and72h after the opening. Thecognitive function was further assessed at1week,3months and6months. Results:Limb remote ischemic preconditioning reduced release of S-100B at6,24,48and72hafter the opening, while it also significantly reduced release of NSE at24,48, and72hafter the opening (P＜0.05). Although the two groups patients cognitive functionassessment is no statistical difference, but RIPC group score better than control.Conclusion: The limb ischemic preconditioning might have certain protective effecton cerebral ischemia and reperfusion injury of the patients with of the heart bypass surgery in perioperative period, which was indicated by serum deceasing of S-100Band NSE release.