Feasibility of multimodal metabolic analysis for detecting early changes in acute neuroinflammation.

Overview

1. Oxford Centre for Clinical Magnetic Resonance Research, Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital,Headley Way, Headington, Oxford, OX3 9DU UK
2. Department of Radiology, Oxford University Hospitals,Oxford, UK
3. Department of Physiology, Anatomy, and Genetics, University of Oxford,Oxford, UK
4. Turku Bioscience Centre, University of Turku and Åbo Akademi,Tykistökatu 6, Turku, FI- 20520 Finland
5. School of Medical Sciences, Faculty of Medicine and Health, Örebro University,Örebro, Sweden
6. Department of Chemistry, University of Turku,Tykistökatu 6, Turku, FI-20520 Finland
7. Nuffield Department of Clinical Neurosciences,Dorothy Hodgkin Crowfoot Building, Sherrington Road, Oxford, OX1 3QU UK

Abstract

Given the prevalence of metabolic perturbations in a variety of neurological and neurodegenerative diseases, understanding and monitoring brain metabolism is a key step in our advancement of therapies. The details of the citric acid cycle were established at the beginning of the last century but only recently have its metabolic intermediates been observed in vivo in the brain. In this study, we employed orthogonal analyses to investigate metabolic alterations in response to acute neuroinflammation in vivo, demonstrating a multi-technique approach that could be used for future studies.

Hyperpolarized [1-13C] pyruvate spectroscopy revealed an early decline in pyruvate metabolism via pyruvate dehydrogenase (PDH), leading to reduced 13C-bicarbonate formation. This metabolic disruption occurred despite the absence of structural or perfusion changes on conventional MRI. Further analysis of polar metabolites in the ipsilateral hemisphere confirmed ongoing inflammatory processes. These findings highlight the potential of this dual technique approach to inform upon metabolic changes due to neuroinflammation.

Combining methods to probe metabolism in invasive (metabolomics) and non-invasive (hyperpolarized MRI) manners, this represents a promising translational approach for real-time metabolic assessments in an area of the body, the brain, where studying processes such as metabolism has traditionally been challenging. This study has demonstrated the approach to monitor changes in metabolism in response to inflammation in the brain.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12974-026-03839-7.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• figshare:32918233, at figshare; found in DataCite
• figshare:32918236, at figshare; found in DataCite
• figshare:32918239, at figshare; found in DataCite
• figshare:32918245, at figshare; found in DataCite
• figshare:32918248, at figshare; found in DataCite

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 11 MeSH terms, 5 funders, 44 references.

Cite

This paper

Grist, J. T., Evstafev, I., Olesova, D., Nynäs, S. E., Orešič, M., Dickens, A. M., Tyler, D. J., & Couch, Y. (2026). Feasibility of multimodal metabolic analysis for detecting early changes in acute neuroinflammation. Journal of neuroinflammation, 23(1), 228. https://doi.org/10.1186/s12974-026-03839-7

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