Neuroprotective Effects of Ischemic Preconditioning on Global Brain Ischemia through Up-Regulation of Acid-Sensing Ion Channel 2a

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.

Keywords

• acid-sensing ion channel 2a
• ischemic preconditioning
• global brain ischemia
• neuroprotection