Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia-reperfusion (GCIR)-induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest-cardiopulmonary resuscitation (CA-C PR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal death in GCIR- injured brain post-CA-C PR. Using normal controls (Sham group) and two experimental groups [CA-C PR- induced GCIR injury (PCA S) group and exogenous treatment with adiponectin post-CA-C PR (APN group)], it was demonstrated that both apoptosis and autophagy were observed simultaneously in the brain subjected to GCIR, but apoptosis appeared to be more apparent. Exogenous administration of APN significantly reduced the formation of malondialdehyde, a marker of oxidative stress and increased the expression of superoxide dismutase, an anti-oxidative enzyme, resulting in the stimulation of autophagy, inhibition of apoptosis and reduced brain tissue injury (P<0.05 vs. PCA S). APN treatment increased the expression of APN receptor 1 (AdipR1) and the phosphorylation of AMP-activated protein kinase (AMPK; Ser182) in brain tissues. In conclusion, GCIR induced apoptosis and inhibited autophagy, contributing to brain injury in CA-C PR. By contrast, APN reduced the brain injury by reversing the changes of neuronal autophagy and apoptosis induced by GCIR . The possible mechanism might owe to its effects on the activation of AMPK after combining with AdipR1 on neurons, which suggests a novel intervention against GCIR injury in CA-C PR conditions.
He, Yarong; Liu, Bofu; Yao, Peng; Shao, Yuming; Cheng, Yanwei; Zhao, Jie; Wu, Jiang; Zhao, Zhi Wei; Huang, Wen; Christopher, Theodore A.; Lopez, Bernard; Ma, Xin-Liang; and Cao, Yu, "Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation‑induced apoptosis in brain by increasing autophagy involved in AdipoR1‑AMPK signaling." (2020). Department of Emergency Medicine Faculty Papers. Paper 124.
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