Mitophagy in the Hippocampus Is Excessive Activated After Cardiac Arrest and Cardiopulmonary Resuscitation
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This study examined the activation of mitophagy following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) and the relationship between the change with time and apoptosis. Main methods: The male Sprague–Dawley rats were randomized into four groups: Sham group, CPR24h group, CPR48h group, CPR72h group. The rat model of cardiac arrest was established by asphyxiation. We employed western blot to analyze the levels of mitophagy related proteins of hippocampus, JC-1 to detect mitochondrial membrane potential (MMP) and flow cytometry to measure the rate of apoptosis of hippocampal neurons. Moreover, we also intuitively observed the occurrence of mitophagy through electron microscopy. Key findings: The results showed that the levels of TOMM20 and Tim23 protein were significantly decreased after CPR, which were more remarkable following 72 h of CPR. However, the protein levels of dynamin related protein 1 (Drp1) and cytochrome C (Cyt-c) were strongly up-regulated after CPR. Meanwhile, the hippocampal MMP decreased gradually with time after CPR. Furthermore, we more intuitively verified the activation of mitophagy through electron microscopy. In addition, the rats of apoptosis rate of hippocampus after CPR were significantly increased, which were gradually enhanced over time from 24 h until at least 72 h following CPR. Significance: with the enhancement of mitophagy, the apoptosis of hippocampal neurons was gradually enhanced, which suggested mitophagy may be excessive activated and aggravating brain damage after CA and CPR.
KeywordsCardiac arrest Cardiopulmonary resuscitation Mitophagy Apoptosis Hippocampus Ischemic reperfusion injury
This work was supported by the National Natural Science Foundation of China (Grant No. 81471831). We thank the Laboratory of cardiac surgery of Tongji Medical College of HuaZhong University of Science and Technology for the help of providing experimental equipment and technical guidance.
Compliance with Ethical Standards
Conflicts of interest
All the authors declare that they have no competing interests.
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