Unraveling Metabolic Changes following Stroke: Insights from a Urinary Metabolomics Analysis

The neuropathological sequelae of stroke and subsequent recovery are incompletely understood. Here, we investigated the metabolic dynamics following stroke to advance the understanding of the pathophysiological mechanisms orchestrating stroke recovery. Using a nuclear magnetic resonance (NMR)-driven metabolomic profiling approach for urine samples obtained from a clinical group, the objective of this research was to (1) identify novel biomarkers indicative of severity and recovery following stroke, and (2) uncover the biochemical pathways underlying repair and functional recovery after stroke. Urine samples and clinical stroke assessments were collected during the acute (2-11 days) and chronic phases (6 months) of stroke. Using a 700 MHz ¹H NMR spectrometer, metabolomic profiles were acquired followed by a combination of univariate and multivariate statistical analyses, along with biological pathway analysis and clinical correlations. The results revealed changes in phenylalanine, tyrosine, tryptophan, purine, and glycerophospholipid biosynthesis and metabolism during stroke recovery. Pseudouridine was associated with a change in post-stroke motor recovery. Thus, NMR-based metabolomics is able to provide novel insights into post-stroke cellular functions and establish a foundational framework for future investigations to develop targeted therapeutic interventions, advance stroke diagnosis and management, and enhance overall quality of life for individuals with stroke.