Abstract

Objective Cerebral ischemia-reperfusion injury (CIRI) involves oxidative stress and endothelial dysfunction. The objective of this study is to elucidate the underlying mechanisms through which ropivacaine (RPV) mitigates the CIRI. Methods A transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model was established in 8-week-old male mice to mimic CIRI in vivo . Mice were treated with RPV or positive control edaravone. Cortical injury was evaluated via TTC staining, hematoxylin-eosin staining, and TUNEL assays. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in cortical tissue were measured. In vitro , bEnd.3 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) and treated with RPV. Cell viability was evaluated, while oxidative stress markers ROS, MDA, and SOD were assayed. Western blotting (WB) evaluated 5-hydroxytryptamine receptor 7 (Htr7) and cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling proteins in cortical tissue and bEnd.3 cells. Gene knockdown of Htr7 was performed to validate the role of Htr7/cAMP-PKA in the in vitro and in vivo effects of RPV. Results RPV upregulated Htr7 expression in mouse cortical tissues surrounding the infarct and alleviated CIRI, as shown by reduced infarct volume, lower ROS and MDA levels, and increased SOD activity. RPV reduced oxidative stress in bEnd.3 cells and activated the cAMP-PKA pathway. Knockdown of Htr7 attenuated the protective effects of RPV, while cAMP-PKA activation suppressed endothelial oxidative stress. Conclusion RPV alleviates CIRI by upregulating Htr7 expression, activating the cAMP-PKA signaling, and reducing endothelial oxidative stress.