THE PROTECTIVE EFFECT OF C23 IN A RAT MODEL OF CARDIAC ARREST AND RESUSCITATION

Background: Systemic inflammation acts 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, we hypothesize that C23 reduces systemic inflammation after CA/CPR by blocking the binding of CIRP to TLR4. Methods: Adult male SD rats in experimental groups were subjected to 5 min of CA followed by resuscitation. C23 peptide (8 mg/kg) or normal saline was injected intraperitoneally at the beginning of the return of spontaneous circulation (ROSC). Results: The expressions of CIRP, TNF-alpha, IL-6, and IL-1 beta in serum and brain tissues were significantly increased at 24 h after ROSC (P < 0.05). C23 treatment could markedly decrease the expressions of TNF-alpha, IL-6, and IL-1 beta in serum (P < 0.05). Besides, it can decrease the expressions of TLR4, TNF-alpha, IL-6, and IL-1 beta 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). Conclusions: These findings suggest that C23 can reduce systemic inflammation and it has the potential to be developed into a possible therapy for post-CA syndrome.