Abstract
Transient forebrain or global ischemia induces cell death in vulnerable CA1 pyramidal neurons. A brief period of ischemia, i.e., ischemic preconditioning, affords CA1 neurons robust protection against a subsequent, more prolonged ischemic challenge. Using the four-vessel occlusion model, we established an ischemic preconditioning model in which rodents were subjected to 3 min of sublethal ischemia 48 h before a 15 min lethal ischemia. We showed that preconditioning attenuated the ischemia-induced neural cell death and DNA fragmentation in the hippocampal CA1 region. RT-PCR and western blot analysis showed that preconditioning prior to an ischemic insult significantly increased ASIC 2a mRNA and protein expression in comparison to the ischemic insult alone (p < 0.01). These findings implicate a new role of ASIC 2a on endogenous neuroprotection from ischemic insult.
Highlights
Ischemic stroke, which results from cardiac arrest, cerebral arterial occlusion, or severe vasospasm after subarachnoid ischemia, causes devastating damage to the brain and represents a serious global health problem [1,2,3,4]
Further studies showed that global ischemia up-regulated the expression of Acid-sensing ion channels (ASICs) 2a, a finding that is in accordance with a previous study [27]
We found that preconditioning increased the ASIC 2a mRNA and protein to a level higher than that induced by a single ischemic insult
Summary
Ischemic stroke, which results from cardiac arrest, cerebral arterial occlusion, or severe vasospasm after subarachnoid ischemia, causes devastating damage to the brain and represents a serious global health problem [1,2,3,4]. Oxygen depletion forces the brain to switch to anaerobic glycolysis. The accumulation of lactic acid as a byproduct of glycolysis together with the production of protons by ATP hydrolysis cause a drop in the pH of the ischemic brain. The molecular mechanisms underlying both ischemic cell death and ischemia tolerance are largely unknown. Understanding the molecular basis of these phenomena is likely to provide new therapeutic strategies for this devastating neurological problem
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