Targeting CX3CR1 Signaling Dynamics: A Critical Determinant in the Temporal Regulation of Post-Stroke Neurorepair.

Abstract

Ischemic stroke ranks among the top global causes of disability and mortality, with a highly dynamic pathological process. Post-stroke neuroinflammation, mediated by microglia, demonstrates a dual role in both injury and repair. The CX3CR1/CX3CL1 signaling axis, highly expressed in microglia, acts as a key regulator. This review examines the spatiotemporal dynamics of the axis across the stroke process and its involvement in neural repair. Crucially, this signaling pathway demonstrates stage-dependent functional duality: its cellular sources, receptor expression profiles, and functional consequences undergo temporally orchestrated shifts, manifesting coexisting or interconverting protective and damaging properties. Ignoring this dynamism compromises the therapeutic efficacy of targeted interventions. Thus, we propose a triple precision strategy of "stroke phase-biomarker-targeted intervention". It uses specific biomarkers for precise staging and designs interventions based on each phase's signaling characteristics. Despite challenges like biomarker validation, mechanistic exploration, and cross-species differences, integrating cutting-edge technologies such as spatial metabolomics and AI-driven dynamic modeling promises to shift stroke therapy toward personalized spatiotemporal programming. Temporally targeting CX3CR1 signaling may offer a key basis for developing next-generation precision neural repair strategies for stroke.