Neuroprotection in acute ischemic stroke: promising pharmacological strategies beyond thrombolysis and thrombectomy

Abstract

Acute ischemic stroke (AIS) remains one of the leading causes of mortality and long-term disability worldwide. Although intravenous thrombolysis and mechanical thrombectomy have substantially improved clinical outcomes, their effectiveness is limited by narrow therapeutic windows, restricted accessibility, contraindications, and the risk of reperfusion injury. Consequently, increasing attention has been directed toward pharmacological neuroprotection targeting the ischemic cascade. This review aimed to evaluate emerging pharmacological neuroprotective strategies in AIS beyond established reperfusion therapies, with particular emphasis on the ischemic cascade as a therapeutic target and on selected pharmacological agents with potential neuroprotective efficacy. A narrative literature review was conducted focusing on the pathophysiology of ischemic brain injury and the current evidence regarding the neuroprotective potential of fingolimod, citicoline, and Cerestat. The analysis included randomized clinical trials, meta-analyses, and experimental studies investigating their neuroprotective and neuroreparative mechanisms of action and clinical efficacy. The ischemic cascade represents a promising target for adjunctive therapeutic interventions in AIS. Fingolimod demonstrated beneficial immunomodulatory effects and stabilization of the blood–brain barrier, particularly when administered in combination with reperfusion therapies. Citicoline exhibited pleiotropic neuroprotective and neuroreparative properties, with the greatest clinical benefit observed among patients who did not receive thrombolytic therapy; however, its efficacy appears less pronounced in the context of contemporary stroke management. Effective neuroprotection in AIS is likely to require a multimodal, individualized therapeutic strategy targeting multiple components of the ischemic cascade.