An integrated investigation of systemic and localized pathophysiological mechanisms of stroke and multimodal therapeutic strategies.

Stroke can trigger complex systemic pathophysiological responses. By systematically reviewing the pathophysiological mechanisms following stroke and comprehensive intervention strategies, this review proposes a conceptual framework of a self-amplifying vicious cycle comprising neuroinflammation, mitochondrial failure, blood-brain barrier disruption, and microcirculatory no-reflow, while emphasizing the central role of neurovascular unit injury. Furthermore, multimodal approaches, including acute reperfusion therapy, endogenous neuroprotection, neuromodulation, and intelligent rehabilitation, are precisely mapped onto the corresponding cellular and molecular targets within this vicious cycle. Combined with standardized secondary prevention, these approaches are integrated into a standardized continuum-of-care pathway. This review advocates a shift in the diagnostic and therapeutic paradigm from single-target intervention toward multimodal, systemic, and comprehensive intervention, providing guidance for future precision medicine and clinical translation.