Liraglutide attenuates post-cardiac arrest brain injury by inhibiting autophagy and ferroptosis

Abstract

Abstract Post-cardiac arrest brain injury (PCABI) is the leading cause of death and disability in survivors of cardiac arrest (CA), where autophagy and ferroptosis are believed to play a pivotal role. Liraglutide, a synthetic, long-acting glucagon-like peptide-1 (GLP-1) analog, can exert organ-protective effects through regulating autophagy and ferroptosis. This study aimed to investigate whether liraglutide had a neuroprotective after cardiac arrest and cardiopulmonary resuscitation and explore its potential mechanisms. We used the 8-min asphyxial cardiac arrest and cardiopulmonary resuscitation model in Sprague–Dawley rats to determine the possible mechanism. The histological changes, proinflammatory factors, apoptosis, autophagy and ferroptosis in hippocampal tissues were detected. Furthermore, the neurologic deficits scores (NDS) and 7-day survival rate was observed respectively. Our results showed that autophagyand apoptosis were activated and the expressions of proteins reached significance at 24h after CA/ROSC. Moreover, rapamycin enhanced apoptosis, ferroptosis and aggravated neuro-pathological damage while 3-methyladenine reduced that. Furthermore, liraglutide treatment improved the 7-day survival rate and NDS, reduced histology injury and inhibited apoptosis, ferroptosisand inflammatory cytokines released after cardiac arrest, and these effects were offset by autophagy agonist. These results suggested that liraglutide could exert a protective role against post-cardiac arrest brain injury, which could be partially mediated by partially inhibiting autophagy and ferroptosis.