Difference in acute and chronic stage ischemic stroke metabolic markers with controls

Area of Science:

• Biochemistry
• Neurology
• Metabolomics

Background:

• Acute ischemic stroke (AIS) is a leading cause of disability with previously inconsistent metabolomic findings.
• Contradictory results may stem from differing study designs (case-control, longitudinal).
• This study aimed to clarify metabolomic alterations by comparing AIS patients across acute and chronic stages with controls simultaneously.

Purpose of the Study:

• To identify specific serum metabolite changes associated with the acute stage of ischemic stroke.
• To differentiate metabolites altered in stroke patients compared to controls, irrespective of stroke phase.
• To provide a clearer understanding of the metabolomic landscape in AIS.

Main Methods:

• Utilized a nuclear magnetic resonance (NMR) platform to analyze 271 serum metabolites.
• Included a cohort of 297 AIS patients (acute and chronic stages) and 159 controls.
• Employed Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) and multivariate/mixed regression, with false discovery rate (FDR) correction.

Main Results:

• sPLS-DA demonstrated clear separation between acute AIS, chronic AIS, and control metabolomes.
• Identified 38 significantly altered metabolites; ketones, BCAAs, energy, and inflammatory markers were elevated in the acute stage.
• Metabolite levels shifted in the chronic stage, often returning towards control levels, while lipid classes differed consistently from controls.

Conclusions:

• Identified distinct metabolite profiles for acute ischemic stroke.
• Characterized metabolites altered in stroke patients versus controls, independent of stroke acuity.
• Highlights the need for validation in larger cohorts to confirm these pilot findings.