Deciphering the disease ecosystem of ischemic stroke via multi-omics and prospects for therapeutic strategies

Ischemic stroke (IS) remains a leading cause of disability due to the translational failure of single-target therapies, underscoring the limitations of the traditional neuron-centric view. This review proposes a paradigm shift by conceptualizing IS as a dynamically evolving “disease ecosystem.” We integrate multi-omics evidence to delineate five interconnected core features—cellular identity collapse, inflammatory-reparative imbalance, neurovascular unit disintegration, brain-peripheral immune miscommunication, and extracellular matrix scarring—that form a pathological logic axis driving disease progression. Based on this systemic understanding, we advance the novel therapeutic strategy of “ecosystem engineering,” which emphasizes temporally adaptive, spatially precise, and network-coordinated interventions. This framework aims to overcome current therapeutic bottlenecks and usher in a new era of precision neural repair.