Involvement Of Extracellular Signal Regulated Kinase And Neuroglobin In Cerebral Ischemic Tolerance Induced By Limb Ischemic Preconditioning In Rats

Ischemic neuropathy is a major cause of morbidity and mortality in neurology, which does harm to human health seriously. Ischemic preconditioning is a phenomenon that a brief episode of sublethal ischemia and other nonlethal stressors protect organs or tissues against a subsequent lethal ischemic insult. Ischemic preconditioning was identified first in the heart, and was demonstrated subsequently in many organs, including brain, in different species. Recently, with profound studies of ischemic preconditioning, protective effect of remote organ preconditioning which was a brief episode of sublethal ischemia in an organ remote from the target organ, was found. This provided a possibility for applying transient ischemic preconditioning in non-vital organs to protect the target organ against severe ischemia. Up to now, most investigations on remote organ preconditioning focused on the heart and kidney. Our recent study demonstrated that limb ischemic preconditioning (LIP) could attenuate delayed neuronal death (DND) or apoptosis of pyramidal neurons in the CA1 hippocampus induced normally by serious brain ischemia/reperfusion and yield cerebral protection. However, the mechanism of the neuroprotection of LIP has not been well understood.Extracellular signal-regulated kinase 1/2 (ERK1/2) is a classical signal transduction pathway of the mitogen-activated protein kinase (MAPK) family. ERK1/2 was thought to be associated with neuronal proliferation, differentiation, and inhibiting apoptosis. In response to extracellular stimuli, ERK1/2 translocates to nucleus, phosphorylates transcription factors,such as Elk1,ATF2,Sap-1α,c-myc,STAT, and so on, co-regulators and chromatin proteins to initiate transcriptional changes. Then the upregulation of these genes (for example, immediate early genes, late effector genes, and heat shock...