LAUSR

BACKGROUND Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the central nerve system can alleviate neurological deficits after induction of CA and further determine the engagement of PIC signal in the hippocampus in the effects of amiloride. METHODS CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1a in the hippocampus, and the levels of PICs. RESULTS CA increased ASIC1a in the hippocampus of rats as compared with control animals. This was companied with increases of IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. Infusion of amiloride into the lateral ventricle attenuated upregulation of Caspase-3/Caspase-9 and this further improved neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1a in the hippocampus of CA rats. CONCLUSION Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the central nerve system plays a neuroprotective role in the pathophysiological process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) has clinical implications for treatment and improvement of CA-evoked global cerebral ischemia often observed in clinics.