Time-dependent plasma metabolic shifts and mechanistic insights into systemic consequences of cerebral ischemia in middle-aged patients.

objectivesTo investigate how acute ischemic stroke induces systemic metabolic reorganization and to characterize the temporal dynamics of these alterations in relation to stroke severity.

methodsBlood plasma samples were collected from patients (n = 42) with acute ischemic stroke, including individuals undergoing mechanical thrombectomy, at two time points: within 24 h and five days after stroke onset. Analysed were circulating metabolites linked to energy metabolism and the most abundant amino acids.

resultsStroke triggered rapid and systemic metabolic changes, including altered circulating glucose and lactate levels indicative of shifts in substrate utilization and inter-tissue energy redistribution. Ketone body concentrations were elevated, providing alternative fuels for metabolically stressed tissues. The magnitude and timing of systemic changes, including dynamic modulation of amino acids, were proportional to ischemic severity, demonstrating a graded physiological response.

conclusionThis study provides a characterization of the dynamic metabolic response to acute ischemic stroke, revealing extensive alterations in energy metabolism, amino acid pathways, and systemic metabolic regulation. Certain exhibited rapid changes that nearly normalized by Day 5, whereas other metabolites, including specific amino acids, showed delayed responses, highlighting the temporal heterogeneity of post-stroke metabolic response. The interconnection of metabolic pathways underscores that post-stroke alterations extend beyond isolated processes, forming a systemic network of biochemical interactions that may affect recovery trajectories and peripheral organ function. These findings provide insight into inter organ-level coordination after stroke and highlight the potential of plasma metabolomic profiling for monitoring systemic responses and recovery following cerebral ischemic events.