Research reportRemote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats

- Histological evidences for neuroprotection induced by remote ischemic preconditioning (RIPC) in cardiac arrest (CA) rats are proposed.
- RIPC up-regulates neuroglobin (Ngb) expression in CA rats.
- The neuroprotection relies on Ngb overexpression.

In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90 min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24 h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia, followed by 5 min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6 min. Defibrillation was attempted after 6 min of cardiopulmonary resuscitation. The animals were then monitored for 2 h and observed for an additionally maximum 70 h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72 h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72 h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24 h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated neuroprotection of remote ischemic preconditioning. These date suggested that neuroglobin involved in neuroprotective effect of remote ischemic preconditioning. In conclusion, remote ischemic preconditioning attenuated post resuscitation cerebral dysfunction and the neuroprotection was mediated partly by high level of neuroglobin in a rat model of cardiac arrest and resuscitation.