Post-stroke neuroplasticity: Spatiotemporal multicellular networks and traditional Chinese medicine interventions

Stroke remains a leading cause of disability and mortality worldwide. Although reperfusion therapy has improved clinical outcomes in the acute phase, long-term functional recovery remains limited. Neuroplasticity, a fundamental basis for functional recovery, is increasingly recognized as a multicellular interactive process rather than a neuron-centric phenomenon. In this context, traditional Chinese medicine (TCM) and phytomedicine may provide unique therapeutic value because of their multi-component, multi-target, and network-level regulatory properties.

This review aims to summarize the multicellular interaction networks involved in post-stroke neuroplasticity and elucidate their spatiotemporal regulatory mechanisms in neural repair, with particular attention to the potential role of TCM-based network modulation.

Narrative review.

Relevant studies on neurons, astrocytes, microglia, oligodendrocyte lineage cells, peripheral immune cells, inflammatory mediators, phytomedicinal compounds, TCM formulas, and neuroplasticity after stroke were narratively reviewed and synthesized to construct an integrated framework of multicellular interaction networks.

Following stroke, neurons, astrocytes, microglia, oligodendrocyte lineage cells, and peripheral immune cells form dynamic multicellular interaction networks that reshape the inflammatory microenvironment through cytokines, neurotrophic factors, extracellular vesicles, and other signaling mediators. These networks regulate post-stroke neuroplasticity in a stage-dependent and region-specific manner. Temporally, neuroplasticity evolves from acute injury-dominant inflammatory activation to subacute repair initiation and later network reorganization. Spatially, the infarct core, ischemic penumbra, and distant brain regions exhibit distinct inflammatory states, cellular responses, repair potential, and therapeutic priorities. Importantly, gray matter synaptic remodeling and white matter repair follow asynchronous trajectories, suggesting that post-stroke neural repair requires temporally and spatially matched interventions. Within this framework, TCM may act as multi-component and multi-target network modulators capable of simultaneously regulating neuroinflammation, glial responses, synaptic remodeling, and white matter repair. Accordingly, precision repair strategies should be designed as stage-specific and region-specific interventions targeting multicellular interaction networks rather than as uniform therapeutic approaches.

Multicellular interaction networks play a central role in regulating post-stroke neuroplasticity. Understanding their spatiotemporal characteristics may facilitate the development of stage-specific, region-specific, and individualized neural repair strategies for stroke treatment. TCM-guided multi-target modulation represents a promising strategy aligned with this network-level repair framework, although further mechanistic and clinical validation is still needed.