---
title: "Spatiotemporal Immunometabolic Remodeling After Acute Traumatic Brain Injury Revealed by Labeled P"
id: "biorxiv-4-distinct-spatiotemporal-immunometabolic-remodeling-following-acute-traumatic"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-distinct-spatiotemporal-immunometabolic-remodeling-following-acute-traumatic"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1?rss=1"
published_at: "2026-07-29T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Spatiotemporal Immunometabolic Remodeling After Acute Traumatic Brain Injury Revealed by Labeled P
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-distinct-spatiotemporal-immunometabolic-remodeling-following-acute-traumatic
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1?rss=1)
- **Published At:** 2026-07-29T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study used matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging combined with in vivo administration of isotopically labeled **pyruvate** and immunohistochemistry in a controlled cortical impact rat model to evaluate metabolic changes after acute traumatic brain injury (TBI). - Investigators characterized cell type–specific and regionally distinct metabolic remodeling across neurons, **astrocytes**, and **microglia** during acute and subacute phases of injury. - Regions enriched for **microglia** and macrophages showed selective accumulation of **citrate**, **succinate**, and **itaconate**, consistent with an inflammatory immunometabolic phenotype. - **Astrocyte**-enriched areas displayed increased **glutamine** and **malate**, suggesting altered neuron–astrocyte coupling, remodeling of the glutamate–glutamine cycle, and enhanced anaplerotic metabolism. - Labeled isotopologues of metabolites such as **glutamate** and **citrate** derived from administered pyruvate changed before total metabolite pool sizes, indicating early flux alterations precede steady-state concentration shifts. - The metabolic signatures showed distinct spatial and temporal distributions, indicating compartmentalized responses within the injured brain. - Authors propose these compartmentalized immunometabolic responses identify candidate metabolic pathways for therapeutic targeting and for metabolic imaging, though detailed therapeutic proposals and validation beyond these observations were not reported in the source.
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Zohreh Erfani 1 The University of Texas Southwestern Medical Center; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Zohreh%2BErfani%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Erfani%20Z&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AZohreh%2BErfani%2B) * [ORCID record for Zohreh Erfani](http://orcid.org/0000-0002-6754-5684 "Open in new tab") Erin H Seeley 2 The University of Texas MD Anderson Cancer Center; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Erin%2BH%2BSeeley%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Seeley%20EH&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AErin%2BH%2BSeeley%2B) * [ORCID record for Erin H Seeley](http://orcid.org/0000-0002-8000-5754 "Open in new tab") Erik J Plautz 1 The University of Texas Southwestern Medical Center; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Erik%2BJ%2BPlautz%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Plautz%20EJ&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AErik%2BJ%2BPlautz%2B) * [ORCID record for Erik J Plautz](http://orcid.org/0000-0001-8949-3064 "Open in new tab") Brenda L Bartnik-Olson 3 Loma Linda University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Brenda%2BL%2BBartnik-Olson%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bartnik-Olson%20BL&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ABrenda%2BL%2BBartnik-Olson%2B) * [ORCID record for Brenda L Bartnik-Olson](http://orcid.org/0000-0002-1137-9437 "Open in new tab") Jae Mo Park 4 University of Texas Southwestern Medical Center * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jae%2BMo%2BPark%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Park%20JM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJae%2BMo%2BPark%2B) * [ORCID record for Jae Mo Park](http://orcid.org/0000-0002-7404-6971 "Open in new tab") * For correspondence: jaemo.park@utsouthwestern.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5663597/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5663597/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5663597/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5663597/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5663597/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Traumatic brain injury induces profound metabolic reprogramming across neurons, astrocytes, and microglia, yet the spatiotemporal organization of these metabolic responses remains poorly understood. Because pyruvate is uniquely positioned in cerebral metabolism by connecting glycolysis, lactate metabolism, and the tricarboxylic acid cycle, we combined matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging with in vivo administration of isotopically labeled pyruvate and immunohistochemistry to characterize cell-type-wise metabolic remodeling in a controlled cortical impact rat model during the acute and subacute phases of injury. TBI induced distinct spatiotemporal immunometabolic remodeling across neuroglial compartments. Microglia- and macrophage-enriched regions exhibited selective accumulation of citrate, succinate, and itaconate, consistent with inflammatory metabolic rewiring. In contrast, astrocyte enriched regions showed increased glutamine and malate abundance, indicative of altered neuron-astrocyte metabolic coupling such as remodeling of the glutamate-glutamine cycle and enhanced anaplerotic metabolism. These metabolic signatures evolved with distinct regional and temporal distributions, identifying compartmentalized metabolic responses. Notably, labeled isotopologues of selected metabolites, including glutamate and citrate derived from administered pyruvate, changed before the corresponding metabolite pools. Together, these findings describe the spatiotemporal landscape of immunometabolic remodeling following acute TBI, uncover metabolically distinct microglial/macrophage and astrocytic responses during secondary brain injury, and identify candidate metabolic pathways for therapeutic intervention and metabolic imaging. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared National Institute of Neurological Disorders and Stroke, https://ror.org/01s5ya894, R01NS107409 National Institute of Diabetes and Digestive and Kidney Diseases, https://ror.org/00adh9b73, P30DK127984 National Heart, Lung, and Blood Institute Division of Intramural Research, https://ror.org/023ny1p48, R01HL170039 Office of the Director, https://ror.org/00fj8a872, S10OD028490 Cancer Prevention and Research Institute of Texas, RP190617, RP240559, RP210099, RP260736 United States Army Medical Research and Development Command, https://ror.org/03cd02q50, W81XWH2210485, HT94252510616 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/07/29/2026.07.28.740519.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.07.28.740519v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Distinct spatiotemporal immunometabolic remodeling following acute traumatic brain injury Zohreh Erfani, Erin H Seeley, Erik J Plautz, Brenda L Bartnik-Olson, Jae Mo Park bioRxiv 2026.07.28.740519; doi: https://doi.org/10.64898/2026.07.28.740519 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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