Remote Ischemic Postconditioning Inhibits Hippocampal Neuronal Apoptosis and Mitophagy After Cardiopulmonary Resuscitation in Rats

Abstract

Background: Studies have shown that remote ischemic post-conditioning can improve brain damage caused by ischemia and hypoxia. However, the specific mechanism underlying this phenomenon is still unclear. The purpose of this study was to investigate the effects of remote ischemic post-conditioning on neuronal apoptosis and mitophagy after cardiopulmonary resuscitation (CPR) in rats. Methods: Male Sprague-Dawley rats were used to establish an asphyxia cardiac arrest model by clamping the tracheal duct. First, the expression levels of P53, Cytochrome c (Cytc), and Parkin in the cytoplasm and mitochondria were observed at 3, 6, 24, and 72 h after the restoration of spontaneous circulation (ROSC). Then neurological deficit scores, hippocampal neuron apoptosis, mitochondrial P53 and Parkin, cytoplasmic Cytc, and neuron ultrastructure were evaluated 24 h after ROSC. Results: P53 and Parkin can translocate from the cytoplasm to the mitochondria, promoting the translocation of cytoplasmic Cytc to mitochondria after CPR, reaching a peak at 24 h after the ROSC. The P53 inhibitor Pifithrin-m reduced apoptosis induced by P53 mitochondrial translocation. Apoptosis was induced after cardiac arrest and attenuated by remote ischemic postconditioning via inhibiting P53 mitochondrial translocation and the release of Cytc to the cytoplasm. In addition, remote ischemic postconditioning could inhibit Parkin-mediated mitophagy. Conclusion: Taken together, our results show that remote ischemic post-conditioning improves neural function after CPR by inhibiting P53 mitochondrial translocation-induced apoptosis and Parkin-mediated mitophagy.

The molecular mechanism underlying mitophagy‐mediated hippocampal neuron apoptosis in diabetes‐related depression

“…Autophagy, including mitophagy, is a tightly modulated cellular degradation process responsible for the clearance of damaged proteins and organelles 12 . Generally, excessive mitophagy brings about mitochondrial impairment and further triggers hippocampal neuron apoptosis via the death receptor pathway of endogenous 13 . An increasing number of studies also indicate the relationship between autophagy and apoptosis 14,15 .…”

“…12 Generally, excessive mitophagy brings about mitochondrial impairment and further triggers hippocampal neuron apoptosis via the death receptor pathway of endogenous. 13 An increasing number of studies also indicate the relationship between autophagy and apoptosis. 14,15 It has been accepted that increased hippocampal neuron apoptosis plays an important role in the pathogenesis of diabetes-related depression.…”

Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

“…It is predictable that iPostC regulates mitophagy, but the mechanisms involved are unknown. Some evidence supporting this argument comes from studies where remote ischemic postconditioning (RIPostC) inhibits the overactivation of mitophagy [190,191], or those in which Hyp-PostC and RIPostC promote mitophagy through the PINK1/Parkin pathway [192], providing neuroprotective effects against ischemia and hypoxia.…”

Neuroprotective Mechanism of Icariin on Hypoxic Ischemic Brain Damage in Neonatal Mice

“…Previous studies have shown that the activation of autophagy helps to improve the pathological damage caused by neurodegenerative and ischemic diseases. Autophagy induction has been found in both neonatal and adult rodents after HIBD, but its role in HIE is still controversial [ 7 , 34 ]. It has been reported that inhibition of autophagy aggravates neuronal mitochondrial dysfunction and aggravates apoptosis in HIBD pups [ 35 ].…”