Abstract
BACKGROUND: Stroke remains a leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of cases. Advances in reperfusion therapies, including intravenous thrombolysis (IVT) and mechanical thrombectomy (MT), have significantly improved outcomes for acute ischemic stroke patients. However, reperfusion brain injury (RBI), a paradoxical consequence of recanalization, poses a major challenge, driven by oxidative stress, inflammation, and blood-brain barrier disruption. This review critically examines emerging therapeutic strategies to mitigate RBI, focusing on pharmacological agents such as edaravone, NXY-059, and tenecteplase, as well as procedural innovations in thrombectomy. METHODS: This review employed a systematic search of databases such as PubMed, Cochrane Library, Embase, and Scopus using certain keywords. A comparative analysis of thrombolysis and thrombectomy was done, and emerging techniques and drugs mitigating reperfusion brain injury (RBI) were discussed. RESULTS: Thrombolysis and thrombectomy highlight key differences in efficacy, safety, and patient selection criteria. While thrombectomy demonstrates superior outcomes in large vessel occlusions (LVOs), thrombolysis remains a cornerstone for early intervention where thrombectomy is inaccessible. Essential drugs like NXY-059, edaravone, uric acid, N-acetylcysteine, and others are changing the care of RBI after stroke. Newer thrombectomy techniques and technologies are also promising. However, the evident efficacy of these methods is still inconsistent in various patients. While thrombectomy and thrombolysis have the potential to cause post-stroke cognitive decline, thrombectomy leads to better outcomes, but patient-specific factors such as age, previous medical history, infarct volume, and others must be considered. Neurorehabilitation is essential for patient recovery from post-stroke cognitive decline. Strategies such as the use of gas-mediated therapies, pharmacological agents, stem cell therapies, antioxidant nanomedicines, and modulation of specific proteins like sirtuins are emerging treatment techniques and are promising to change the narration of RBI management and impact patient outcomes. CONCLUSION: The review underscores the need for precision medicine approaches, improved imaging for patient selection, and comprehensive longitudinal studies to optimize reperfusion strategies. Targeted interventions addressing oxidative damage and inflammation hold promise for reducing RBI and improving long-term patient outcomes.