Levetiracetam in Stroke: A Narrative Review of Neuroprotective Mechanisms and Therapeutic Potential Publisher Pubmed



Hojjat S H ; Rasouli F ; Fathi Karkan S
Source: Behavioural Brain Research Published:2027

Abstract

Background: Stroke remains of the leading causes of mortality/long-term disability worldwide, with post-stroke seizures and secondary neuronal injury contributing to unfavorable outcomes. Levetiracetam (LEV), the widely used antiepileptic drug in clinical practice, has demonstrated neurobiological effects beyond seizure control in experimental models, raising interest in its potential role in stroke-related neuroprotection and neurological recovery. Objective: To synthesize experimental and clinical evidence on LEV in stroke, focusing on (i) preclinical neuroprotective mechanisms and outcomes and (ii) clinical outcomes in stroke populations, particularly post-stroke seizure management and safety. Methods: We conducted a narrative review informed by a comprehensive literature search of major biomedical databases (PubMed/MEDLINE, Scopus, Web of Science Core Collection, Embase, and Google Scholar) from 2001 to 2025, and eligible studies included preclinical stroke models evaluating LEV and clinical studies involving LEV use in stroke patients. Study selection and data extraction were performed using predefined criteria and risk of bias was further assessed using standardized tools. Due to heterogeneity in stroke models, patient populations, interventions, and outcomes, findings were synthesized narratively and summarized in structured tables. Results: The preclinical literature suggests that LEV may reduce infarct volume and improve neurological outcomes in several ischemic and hemorrhagic stroke models. Reported mechanisms include modulation of neuroinflammatory signaling, attenuation of apoptosis, reduced oxidative stress, and preservation of blood–brain barrier integrity, although methodological limitations and incomplete reporting contribute to uncertainty across studies. In clinical studies, the most consistent evidence supports LEV use for post-stroke seizure treatment and prevention, with generally favorable tolerability compared with older antiepileptic drugs. However, direct clinical evidence supporting LEV as a neuroprotective therapy to improve stroke lesion outcomes or long-term functional recovery remains limited and indirect. Conclusions: Experimental data support biologically plausible neuroprotective effects of LEV in stroke models, while clinical evidence primarily supports its role in post-stroke seizure management and tolerability. The potential for LEV to modify stroke-related neurological injury in humans remains uncertain and requires well-designed clinical trials with stroke-specific neuroprotection endpoints. © 2026 Elsevier B.V.