Key result
Administration of amiloride into the central nervous system attenuated Caspase-3 and Caspase-9 upregulation and alleviated neurological severity score and brain edema in rats following cardiac arrest.
Why the study?
Central pro-inflammatory cytokine signaling contributes to neurological deficits after transient global ischemia induced by cardiac arrest, prompting evaluation of whether blocking acid sensing ion channels with central amiloride alleviates these deficits.
Does amiloride administered into the CNS alleviate neurological deficits following transient global ischemia induced by cardiac arrest in rats?
Does amiloride administered into the CNS alleviate neurological deficits following transient global ischemia induced by cardiac arrest in rats?
Amiloride administered into the CNS plays a neuroprotective role by alleviating neurological deficits and brain edema following cardiac arrest-induced global ischemia in rats.
Does not support clinical use of CNS amiloride post-arrest; leaves open translation of neuroprotection from rat global ischemia models.
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.
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Pang et al. (2019) studied Transient global ischemia induced by cardiac arrest. Amiloride vs. Control animals was evaluated on Neurological severity score, brain edema, and protein expression of ASIC1, Caspase-3, and Caspase-9. Administration of amiloride into the central nervous system attenuated Caspase-3 and Caspase-9 upregulation and alleviated neurological severity score and brain edema in rats following cardiac arrest.
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