P38MAPK Participates In Brain Ischemic Tolerance Induced By Limb Ischemic Preconditioning And The Possible Underlying Mechanisms In Rats

Ischemic cerebrovascular disease is a type of frequently encountered disease in the department of neurology, which has high disability and mortality rate, and severely impairs human health. Because neuronal cells are very sensitive to ischemic injury, long time brain ischemic insult results in brain neuronal death, which can not revive usually and frequently causes many irreversible sequelae. Therefore, how to arouse the endogenous protective mechanisms of organism to enhance the resistance of neurons to ischemic injury is an important strategy in therapy of the ischemic cerebral vascular disease. In 1990, Kitagawa et al found using gerbil brain ischemia model that transient sublethal cerebral ischemia could significantly protect pyramidal neurons in the CA1 hippocampus against delayed neuronal death (DND) normally induced by severe cerebral ischemic insult for 5 min. This phenomenon was called cerebral ischemic tolerance, and the sublethal brain ischemia given in advance was called cerebral ischemic preconditioning. However, this preconditioning might be difficult to be used in clinic. In recent years, with the progress of the studies on ischemic preconditioning, it has been found that an ischemic preconditioning in an organ remote from the target organ could also protect the target organ from ischemic insult. For instance, transient ischemic preconditioning of limbs, small intestine and kidney protected myocardium from the subsequent severe heart ischemic reperfusion. Our recent studies demonstrated that the LIP via 3 cycles of transient occlusion (10 min) and opening of the bilateral femoral arteries immediately before global brain ischemic insult for 8 min could alleviate the subsequent brain ischemic reperfusion injury and increase the survival of the pyramidal neurons in the CA1 hippocampus. These results first confirmed the protective...