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 Nervous System can alleviate neurological deficits after the
induction of CA and further examine the participation of PIC signal in the hippocampus
for the effects of amiloride.
Methods: CA was induced by asphyxia and then cardiopulmonary resuscitation was
performed in rats. Western blot analysis and ELISA were used to determine the protein
expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As
noted, it is unlikely that this procedure is clinically used although amiloride and other
pharmacological agents were given into the brain in this study.
Results: CA increased ASIC1 in the hippocampus of rats in comparison with control
animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with
Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle
attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated
neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also
decreased ASIC1 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 Nervous
System plays a neuroprotective role in the process of global ischemia. Thus, targeting
ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked
global cerebral ischemia.