From Neuroinflammation to Precision Stroke Recovery: A Phase-Specific Immune-Metabolic Framework

Stroke recovery varies markedly among patients and cannot be fully predicted by infarct size, lesion location, or acute treatment success. This variability suggests that recovery is shaped by evolving interactions among neural injury, immune activation, neurovascular integrity, metabolic reserve, and repair-related plasticity. This review proposes a phase-specific immune-metabolic framework for precision stroke recovery. Rather than treating neuroinflammation as a uniformly detrimental process, this review conceptualizes neuroinflammation as a time-dependent biological gate that may either amplify injury or support repair, depending on the phase, cellular context, blood-brain barrier integrity, and systemic metabolic state. In the acute phase, regulated cell death, oxidative stress, inflammasome activation, blood-brain barrier disruption, and proteolytic remodeling contribute to secondary injury and neurovascular instability. During the subacute phase, controlled immune responses may facilitate debris clearance, angiogenesis, synaptic remodeling, and rehabilitation-induced neuroplasticity. In contrast, persistent low-grade inflammation in the chronic phase may impair network reorganization, promote glial reactivity, and contribute to delayed neurodegeneration or poor functional recovery. The available evidence suggests that metabolic and microbiome-related factors are not secondary modifiers but integral components of recovery biology. Nutritional status, sarcopenia, metabolic imbalance, and post-stroke gut dysbiosis may influence immune tone, blood-brain barrier function, microbial metabolite signaling, and neuroplastic potential. These interactions provide a rationale for defining biological recovery endotypes that integrate inflammatory, neurovascular, metabolic, microbiome-related, and plasticity-related signatures. By linking neuroinflammation with immune-metabolic regulation and repair biology, this review reframes stroke recovery as a phase-dependent and biologically stratified process. The framework may support the development of multimodal biomarkers, phase-matched interventions, and patient-stratification strategies for precision stroke recovery trials.