Postconditioning Attenuates Cerebral Ischemia-reperfusion Injury

Background and ObjectiveCerebral ischemic is a high leading cause of disability and death of cerebrovas-cular disease. With society aging of the population, the incidence of ischemic stroke has soared year by year, which has made an Enormous pressure on social and their family.Yet limited therapeutic options exist. The need for novel neuroprotective agents has spurred efforts to understand the Ischemia-reperfusion injury mechanism that mediate cellular response to cerebral ischemic.Cerebral ischemia/reperfusion injury mechanism is unfathomable. There’s a lot of evidence that mitochondrial damage and inflammatory response plays a key role in the pathogenesis.The mitochondrial membrane permeability transition (MPT) is a Ca2+-dependent increase of mitochondrial membrane permeability that leads to loss of△ψ, mitochondrial swelling, and rupture of the outer mitochondrial membrane. Mitochondrial membrane permeability is one of the key events in apoptotic or necrotic death. A large number of studies have also shown that the inflammatory response has been implicated in the pathology of cerebral ischemia-reperfusion injury. Neutrophil invasion is considered to be as a primary mechanism underlying ischemic-reperfusion injury. This’reperfusion injury’involves a well-orchestrated series of interactions between neutrophils and the vascular endothelium via specific adhesion molecules on both cell types; these interactions are initiated in the immediate peri-reperfusion period, and may continue during the ensuing hours and days following reperfusion.Ischemic postconditioning (Postcond) is defined as a series of rapid intermittent interruptions of blood flow in the early phase of reperfusion that mechanically alters the hydrodynamics of reperfusion. In2006, Zhao et al first documented that ischemic postconditioning reduced infarct size in cerebral I/R injury. Protective mechanisms of postconditioning are largely unknown.The protective effects of postconditioning may involve the reduction of the peak generation of reactive oxygen species or the reduction of the release of inflammatory factors during the reperfusion or weakening the cerebral edema. However, it has not been shown previously that the protection by Postconditioning is dependent on affecting the mitochondrial permeability transition, affecting neutrophil infiltration.Accordingly, the present study was designed to test the hypothesis that the Inhibition the mitochondrial permeability transition or reduction ischemic tissue infiltration of neutrophils at the onset of reperfusion is critical to the protection mechanisms of postconditioning.ObjectiveNumerous experimental studies demonstrated a central role for mitochondrial permeability transition (MPT) and neutrophil invasion in the process of cell death after ischemia-reperfusion. Ischemic postconditioning had a proven benefit in the experimental arena of brain ischemia-reperfusion. We tested the hypothesis that Ischemic postconditioning may modulate mPTP opening or Postconditioning may inhibited Neutrophil infiltration.MethodsEighty healthy male Sprague Dawley rats were randomly divided into4groups: sham group (n=20), ischemia-reperfusion group (n=20), ischemic postconditioning group (n=20), delayed ischemic postconditioning group (n=20). Anesthetized rats underwent30minutes of ischemia. Ischemia-reperfusion group rats underwent no additional intervention; sham group rats only exposed carotid artery, but did not insert. Postconditioning consisted of30s of full reperfusion and30s of re-occlusion were repeated for three cycles during the first minute of reperfusion. Delayed Postconditioning consisted of30s of full reperfusion and30s of reocclusion were repeated for three cycles after15minute of reperfusion. The following indexes in4groups were tested respectively:Infarct size, malondialdehyde (MDA), ATP enzyme, myeloperoxidase activity, mitochondrial permeability transition (MPT).ResultsPostconditioning, compared with the ischemia-reperfusion group, significantly reduced infarct size (54.25±3.69%vs.30.81±3.63%, P<0.05)and malondialdehyde levels(1.556±0.081um/g vs.0.865±0.039um/g, P<0.05), enhanced the content of ATPase, inhibited myeloperoxidase activity(0.355±0.304U/g vs.0.235±0.024U/g, P<0.05), attenuated mitochondrial permeability transition(0.299±0.204vs.0.176±0.196, P<0.05). However, Delayed Postconditioning had no such benefit.ConclusionPostconditioning inhibits opening of the mPTP and inhibits Neutrophil infiltration so that it provides a powerful atti-ischemic protection.