• Jun Wu, Yi Li, Peng Yang, Yaping Huang, Shiqi Lu, and Feng Xu.
• 1 Department of Ultrasonography Medicine The Affiliated Suzhou Hospital of Nanjing University of Chinese Medicine Suzhou China.
• J Am Heart Assoc. 2019 May 7; 8 (9): e011851.

AbstractBackground Dysfunctional mitochondria are associated with neurological injury after cardiac arrest ( CA ). Although carbon monoxide ( CO ) has shown various potential therapeutic effects in preclinical tissue injury models, its mechanism of action in CA remains unclear. We sought to investigate the effects of a novel CO -releasing molecule on cerebral mitochondrial dysfunction and neurological injury after CA . Methods and Results Male Sprague-Dawley rats aged 20 to 22 months were subjected to 6-minute asphyxia CA before receiving CO treatment. Survival, neurologic deficit scores, neuronal death, mitochondrial function, and autophagy were evaluated after the return of spontaneous circulation. Results showed that CO post-treatment increased 3-day survival rate from 25% to 70.83% and reduced neurologic deficit scores. CO also ameliorated CA -induced neuronal apoptosis and necrosis in the cerebral cortex and improved cerebral mitochondrial function by reducing reactive oxygen species, reversing mitochondrial membrane potential depolarization, and preventing cytochrome C release. Furthermore, CO increased mitochondrial autophagy by inducing mitochondrial accumulation of PINK 1 ( PTEN -induced putative kinase 1) and Parkin. Downregulation of PINK 1 with genetic silencing si RNA abolished CO -afforded mitochondrial autophagy. Conclusions Taken together, our results indicate, for the first time, that CO treatment confers neuroprotection against ischemic neurological injury after CA possibly by promoting mitochondrial autophagy.

47 keywords...

hide…