Chondroitin Sulfate as a New Profibrinolytic-Like Agent: A Preclinical Proof of Concept in a Model of Thromboembolic Stroke in Mice.

Ischemic stroke requires effective reperfusion therapies to limit brain injury, yet rtPA (recombinant tissue-type plasminogen activator) efficacy is limited, particularly in platelet-rich thrombi. Neutrophil extracellular traps (NETs) and their components, especially histones and DNA, contribute to thrombolysis resistance. Chondroitin sulfate (CS), a glycosaminoglycan with high affinity for extracellular histones, may neutralize their prothrombotic effects and improve outcomes. This study aimed to evaluate the effects of CS in preclinical ischemic stroke models and its impact on components of neutrophil extracellular traps.