Stroke remains a leading cause of global disability, perpetuated by maladaptive neuroinflammation that drives secondary injury and impairs recovery. An early reparative (M2) state rapidly transitions into a dominant destructive (M1) phenotype within days, worsening tissue damage through the release of cytokines tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), blood-brain barrier disruption, and amplified peripheral immune cell infiltration. Emerging pharmacological interventions, such as the free radical scavenger edaravone, the neurotrophic factor cerebrolysin, and the excitotoxicity modulator citicoline, demonstrate promising neuroprotective potential when strategically timed. Additionally, novel non-pharmacological approaches, including repetitive transcranial magnetic stimulation, stem cell therapy, and nanoparticle-based drug delivery, offer innovative pathways for targeting neuroinflammation. However, translational challenges persist, including narrow therapeutic windows, biomarker heterogeneity, and preclinical-to-clinical gaps. Future progress necessitates precision medicine paradigms integrating spatiotemporal drug delivery, biomarker-guided intervention timing, and synergistic combinatorial regimens targeting acute injury and chronic repair phases. By bridging mechanistic insights with clinical applications, this review delineates neuroinflammatory modulation as a pivotal frontier for redefining stroke recovery while outlining essential research trajectories to overcome existing barriers. Systematic search of electronic databases including PubMed, Web of Science, Embase, and Cochrane (1996-2025) was performed, with eligible studies assessed using PRISMA guidelines. Findings on neuroinflammation, mechanism, or interventions in ischemic stroke were narratively synthesized through thematic analysis. This review summarizes current insights into post-stroke neuroinflammatory mechanisms, with a focus on the dual role of microglial polarization.
Chan et al. (2025) studied this question.