The protective effects of distal ischemic treatment on apoptosis and mitochondrial permeability in the hippocampus after cardiopulmonary resuscitation

Abstract

Apoptosis and mitochondrial dysfunction are the main cause of neurological injury after cardiopulmonary resuscitation (CPR). However, the effects of distal ischemic treatments on ischemia induced apoptosis are rarely studied, and the mechanism by which mitochondrial dysfunction contributes to CPR still unclear. A rat model of distal ischemia was established by clipping the right femoral artery. Rats were divided into blank, model, pre distal ischemic treatment, per-treatment, and post-treatment groups. Neurological deficit score was scored to evaluate neurologic function after cardiopulmonary resuscitation for 72 hr. We employed TUNEL and flow cytometry to measure the rate of apoptosis of hippocampal neurons, the integrity of mitochondrial membrane and the degree of mitochondrial permeability transition pore (mPTP) opening. The rate of apoptosis rate of hippocampal CA1 neurons in the pre-treatment and post-treatment groups were significantly lower than that of the model group. Moreover, the integrity of the mitochondrial membrane in the pre-treatment and post-treatment groups was higher than that in the model and per- treatment groups. Furthermore, the degree of mPTP opening was lower in the pre-treatment and post-treatment groups than the untreated and per-treatment groups. Taken together, our results show that ischemic preconditioning and post processing can maintain the integrity of mitochondria, perhaps by inhibiting the opening of mPTP, and reducing apoptosis of hippocampal neurons by regulating expression of apoptosis related proteins after CPR, to improve neurological function. This study highlights a novel target pathway for treatment of CPR.

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

“…In this study, the method of clamping and opening the femoral artery was used to complete the remote ischemic post-conditioning treatment. Our results showed that it can reduce neuronal apoptosis after CPR and improve neurological deficit scores in rats, which is consistent with many related studies (26)(27)(28). However, its endogenous protection mechanism needs further study.…”

Propofol produces neurotoxicity by inducing mitochondrial apoptosis

“…When ROS are overproduced, oxidative stress responses in hippocampal neurons are increased and can lead to apoptosis (29,30). Apoptosis of hippocampal neurons is an important mechanism that maintains homeostasis in the brain, and mitochondrial apoptosis is one of the important pathways in this process (31). Increased activity and expression of caspase-3 and caspase-9 are considered markers of mitochondrial apoptotic pathways activity (32).…”

The Imbalance of Mitochondrial Homeostasis of Peripheral Blood-Derived Macrophages Mediated by MAFLD May Impair the Walking Ability of Elderly Patients with Osteopenia

“…Later, we tested the opening degree of the MPTP using the MPTP Detection Kit (Beyotime Biotech, China), following specific instructions ( http://www.beyotime.com/index.htm ). Flow cytometry was used to analyze the MMP and MPTP opened of the macrophages derived from peripheral blood [ 27 – 29 ].…”