Mitochondrial Function, Oxidative Stress, Inflammation and Thrombolytic Treatment in Ischemic Stroke

Ischemic stroke (IS) is a leading cause of mortality worldwide, responsible for approximately 55% of all neurological disabilities. Proper brain function requires continuous energy supply, primarily generated by mitochondria. Cerebral ischemia impairs the functioning of mitochondrial electron transport chain, reducing adenosine triphosphate production and increasing reactive oxygen species. Inflammation also plays a critical role throughout all stroke phases. YKL-40, a pro-inflammatory glycoprotein, serves as a biomarker of macrophage and microglial activation, while YKL-39 regulates autoimmunity, tissue remodeling, and exhibits monocyte chemotactic and pro-angiogenic activity. This study aims to investigate mitochondrial bioenergetics, oxidative stress, and inflammation in IS patients before and after thrombolysis. Bioenergetic parameters were assessed using Mito Stress Test on an Agilent Seahorse analyzer, and YKL-39, YKL-40 and 4-HNE plasma levels via ELISA. Pre-thrombolytic IS patients demonstrated significantly reduced basal respiration and spare respiratory capacity, along with lower plasma YKL-40 levels. In contrast, they exhibited higher plasma YKL-39 concentrations and increased oxidative stress marker 4-hydroxy-2-nonenal compared to post-thrombolytic patients. These findings highlight novel associations between mitochondrial dysfunction, oxidative stress, and inflammation in IS, and suggest that parameters reflecting these processes may serve as potential biomarkers for evaluating disease severity and predicting outcomes.