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Updated: Aug 9, 2025

Experimental Models to Study the Neuroprotection of Acidic Postconditioning Against Cerebral Ischemia
Published on: July 31, 2017
Carbon monoxide preconditioning is mediated via activation of mitochondrial-derived vesicles
Ying Guo1, Teng Guan2, Xin Jiao3
1Department of Human Anatomy and Cell Science, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada; Department of Forensic Medicine, Hebei North University, 11-South Diamond Road, Zhangjiakou, Hebei, 075000, China.
Abstract:
Preconditioning with inhalative carbon monoxide (CO) at low concentrations provides protection against hypoxic and ischemic insults in the brain and heart. The present study aims to test a hypothesis that activation of mitochondrial-derived vesicles (MDVs) is a mechanism underlying the protective effect of CO preconditioning. Here we show that CO preconditioning induced mild oxidative stress and activated massive production of MDVs. Short exposure to a low concentration of carbon monoxide-releasing molecule 2 (CORM-2), a donor of carbon monoxide, prevented oligodendrocyte precursor cells (OPCs) from subsequent death induced by high doses of CO, and protected Chinese hamster ovary (CHO) cells against oxygen-glucose deprivation (OGD)-induced cell death. Furthermore, inhibition of lysosomal activity prevented degradation of MDVs, abolished MDV-mediated mitochondrial quality control, and diminished the protective effect of CO preconditioning. Altogether, our data provide direct evidence suggesting that MDV-mediated mitochondrial quality control may have a novel role in CO preconditioning.
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