Cognitive impairment after cerebral ischemia-reperfusion injury: a neuroecosystem perspective

Post-stroke cognitive impairment (PSCI) is a common and debilitating neurological complication following cerebral ischemia-reperfusion injury (CIRI). The traditional neuron-centered view cannot fully explain its delayed onset, pathological heterogeneity, and functional plasticity. This review proposes a novel neuroecosystem framework based on the neurovascular-immune-glial (NIG) triad, including a systematic evaluation of the dynamic crosstalk among the neurovascular unit (NVU), neuronal networks, and glial-immune microenvironment. Pathological events, including ferroptosis, neuroinflammation, white matter damage, and gut-brain axis dysfunction, are reinterpreted as manifestations of neuroecosystem collapse, rather than isolated lesions. We further summarize cutting-edge tools, such as spatial omics and in vivo dynamic imaging for framework validation, and clarify how therapeutic strategies are shifting from single neuronal protection to overall ecosystem restoration. Finally, we discuss current limitations in knowledge and future research directions, aiming to provide new insights for mechanistic exploration and clinical intervention of PSCI.