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Cyclosporine A Plus Ischemic Postconditioning Improves Neurological Function in Rats After Cardiac Resuscitation

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Abstract

Background and Objective

Attenuation of neuronal apoptosis helps maintain neurological function in patients after cardiac arrest. After ischemia–reperfusion, both cyclosporin A (CsA) and ischemic postconditioning independently protect mitochondria and thus reduce nerve injury. This study employed a rat model to evaluate the neuroprotective effect of combining ischemic postconditioning with CsA after cardiopulmonary resuscitation (CPR).

Methods

Rats were apportioned equally to model control, postconditioned, CsA-treated, or CsA + postconditioned groups. Asphyxial cardiac arrest was imposed using modified Utstein-style guidelines. In the appropriate groups, postconditioning was implemented by ischemia and reperfusion (clamping and loosening the left femoral artery); CsA treatment was delivered with a single intravenous dose. Neurological deficits were scored at different times after CPR. Histological evaluation and electron microscopy were used to evaluate tissue damage, and TUNEL and flow cytometry were used to measure the apoptotic rate of hippocampal neurons and size of the mitochondrial permeability transition pore (mPTP) opening.

Results

The apoptotic rate was significantly lower in the postconditioned and CsA-treated groups compared with the model control and lowest in the CsA + postconditioned group. By histological evaluation and electron microscopy, the least damage was observed in the CsA + postconditioned group. The neurological deficit score of the CsA + postconditioned group was significantly higher than that of the CsA-treated group, but the size of the mPTP openings of these two groups was comparable.

Conclusion

Ischemic postconditioning combined with CsA exerted a better neuroprotective effect after CPR than did either postconditioning or CsA alone. Inhibiting the opening of the mPTP is not the only neuroprotective mechanism.

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Acknowledgements

We thank the Laboratory of Cardiac Surgery of Tongji Medical College of Huazhong University of Science and Technology for help providing experimental equipment and technical guidance.

Funding

This study is supported by National Natural Science Foundation of China (Grant Number 81471831) and Natural Science Foundation of Hubei Province, China (Grant Number 2017CFB728).

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Contributions

XZ, YQ and SZ conceived and designed the study. XZ, YH, BX and ZT performed the experiments. XZ, YQ, YH, YL and JZ wrote the paper. SZ and GG reviewed and edited the manuscript.

Corresponding author

Correspondence to ShuiBo Zhu.

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Zhou, X., Qu, Y., Gan, G. et al. Cyclosporine A Plus Ischemic Postconditioning Improves Neurological Function in Rats After Cardiac Resuscitation. Neurocrit Care 32, 812–821 (2020). https://doi.org/10.1007/s12028-019-00849-7

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