ROS exhaustion reverses the effects of hyperbaric oxygen on hemorrhagic transformation through reactivating microglia in post-stroke hyperglycemic mice

• Published in: Scientific reports Vol. 14; no. 1; pp. 21410 - 13
• Main Authors: Guo, Yanan, Liu, Jiayi, Du, Xingyue, Qi, Mian, She, Tongping, Xue, Ke, Wu, Xinhe, Xu, Lihua, Peng, Bin, Zhang, Yunfeng, Liu, Yufeng, Jiang, Zhenglin, Li, Xia, Yuan, Yuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-09-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/699/375; 692/699/375/534; Acetylcysteine; Animals; Antioxidants; Antioxidants - pharmacology; Cerebral blood flow; Clinical trials; Disease Models, Animal; Edaravone - pharmacology; Global health; Hemorrhage; Hemorrhagic transformation; Humanities and Social Sciences; Hyperbaric oxygen; Hyperbaric Oxygenation - methods; Hyperglycemia; Hyperglycemia - complications; Hyperglycemia - metabolism; Infarction, Middle Cerebral Artery - therapy; Inflammasomes; Inflammasomes - metabolism; Inflammation; Ischemia; Ischemic stroke; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; multidisciplinary; Neurological diseases; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Oxygen; Public health; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reperfusion; Reperfusion Injury - metabolism; ROS; Science; Science (multidisciplinary); Stroke; Stroke - metabolism; Stroke - therapy; Hemorrhagic transformation; Ischemic stroke; NLRP3 inflammasome; Hyperbaric oxygen; ROS; Microglia
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-72454-4

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and
N
-Acetyl-
l
-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.