The protective effect of a short peptide derived from cold-inducible RNA-binding protein in a rat model of cardiac arrest and resuscitation

Abstract

Abstract Systemic inflammation act as a contributor to neurologic deficits after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Extracellular cold-inducible RNA-binding protein (CIRP) has been demonstrated to be responsible in part for the inflammation through binding to Toll-like receptor 4 (TLR4) after cerebral ischemia. The short peptide C23 derived from CIRP has a high affinity for TLR4, which can inhibit the downstream inflammatory response. We hypothesize that C23 reduces systemic inflammation after CA/CPR by blocking the binding of CIRP to TLR4. Adult male SD rats in experimental groups were subjected to 5 minutes of cardiac arrest followed by resuscitation. C23 peptide (8 mg/kg) or normal saline was injected intraperitoneally at the beginning of the return of spontaneous circulation (ROSC). The expressions of CIRP, TNFα, IL-6, and IL-1β in serum and brain tissues were significantly increased at 24h after ROSC (P < 0.05). C23 treatment could markedly decrease the expressions of TNFα, IL-6, and IL-1β in serum (P < 0.05). Besides, C23 can penetrate the blood-brain barrier and play an anti-inflammatory role in brain tissues. It can decrease the expressions of TLR4, TNFα, IL-6, and IL-1β in the cortex and hippocampus and inhibit the colocalization of CIRP and TLR4 (P < 0.05). In addition, C23 treatment can reduce the apoptosis of hippocampus neurons(P < 0.05). Finally, the rats in the C23 group have improved survival rate and neurological prognosis (P < 0.05). These findings suggest that C23 can reduce systemic inflammation and it has the potential to be developed into a possible therapy for post-cardiac arrest syndrome.