{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:06:19Z","timestamp":1789218379353,"version":"build-2803163510"},"reference-count":29,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"abstract":"<jats:p>\n                    Cerebral microdialysis (CMD) after traumatic brain injury (TBI) has focused on lactate\/pyruvate ratio (LPR), overlooking lactate\u2013pyruvate gradient (LPG, the linear regression slope within a time segment of CMD datapoints) as a proxy for anaerobic activity. We retrospectively applied changepoint detection to the linear lactate\u2013pyruvate relationship (L =\n                    <jats:italic toggle=\"yes\">m<\/jats:italic>\n                    P +\n                    <jats:italic toggle=\"yes\">b<\/jats:italic>\n                    ) over time within patients from two independent CMD-monitored TBI cohorts (Cambridge,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 510; Uppsala,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 81), estimating per-segment LPG (\n                    <jats:italic toggle=\"yes\">m<\/jats:italic>\n                    ) and intercept (\n                    <jats:italic toggle=\"yes\">b<\/jats:italic>\n                    , capturing metabolic variance). In vitro, we tested whether rotenone-induced mitochondrial dysfunction increases LPG in hiPSC-derived neurons, as expected if LPG tracks anaerobic activity. In the Cambridge cohort, a median of two linear segments were identified per patient (median LPG = 19.83; median\n                    <jats:italic toggle=\"yes\">b<\/jats:italic>\n                    = 0.54 mM). Between segments, LPR tracked LPG with heavy attenuation (\u03b2 = 0.255). LPG was negatively associated with cerebral microdialysate glucose (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001) and 6-month GOSE (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.039). Uppsala data confirmed pipeline robustness and replicated the LPG\u2013glucose association (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.022). LPG was higher in rotenone-treated neurons than controls (32.9 vs 14.2,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001). LPG calculated per time segment provides a more accurate, outcome-associated proxy for anaerobic activity than datapoint-level LPR.\n                  <\/jats:p>","DOI":"10.1177\/0271678x261485404","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:44:23Z","timestamp":1787741063000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The microdialysis-derived lactate\u2013pyruvate gradient indicates anaerobic activity after brain injury"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3078-3001","authenticated-orcid":false,"given":"Michael S","family":"Baker","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6151-6410","authenticated-orcid":false,"given":"Joshua M","family":"Heihre","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-8861","authenticated-orcid":false,"given":"Tomasz","family":"Kuli\u0144ski","sequence":"additional","affiliation":[{"name":"Section of Neurosurgery, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3643-6191","authenticated-orcid":false,"given":"Claudia A","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berfin","family":"Barlas","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"},{"name":"Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisomo","family":"Zimphango","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-0393","authenticated-orcid":false,"given":"Ivan","family":"Timofeev","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6887-3241","authenticated-orcid":false,"given":"Koby","family":"Baranes","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"},{"name":"Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri L H","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kotter","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"},{"name":"Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew R","family":"Guilfoyle","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Rostami","sequence":"additional","affiliation":[{"name":"Section of Neurosurgery, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden"},{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0531-0556","authenticated-orcid":false,"given":"Adel","family":"Helmy","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/ACO.0000000000001183"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-0027-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq353"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-4-540"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-012-9708-y"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0260291"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318186a4a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2022.0161"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09541-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-004-2461-8"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-026-05993-z"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2021.0502"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0331310"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X211042112"},{"key":"e_1_3_3_16_2","volume-title":"Contusion progression in traumatic brain injury","author":"Guilfoyle MR","year":"2019","unstructured":"Guilfoyle MR. Contusion progression in traumatic brain injury. PhD Thesis, University of Cambridge, UK, 2019."},{"key":"e_1_3_3_17_2","volume-title":"Lehninger principles of biochemistry","author":"Nelson DL","year":"2021","unstructured":"Nelson DL, Cox MM, Hoskins AA. Lehninger principles of biochemistry. 8th ed. New York: Macmillan Learning, 2021.","edition":"8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03168.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2012.737745"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sigpro.2019.107299"},{"key":"e_1_3_3_21_2","first-page":"166","volume-title":"31st international conference on distributed computing systems workshops","author":"Satopaa V","unstructured":"Satopaa V, Albrecht J, Irwin D, et al. Finding a \u201cKneedle\u201d in a haystack: detecting knee points in system behavior. In: 31st international conference on distributed computing systems workshops, Minneapolis, MN, USA, 20\u201324 June 2011, pp.166\u2013171. New York: IEEE."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.8127224"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2013.00513"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101885"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2007"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16661202"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.02.016"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220937"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24372"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-08194-6"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261485404","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X261485404","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261485404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:24:52Z","timestamp":1789215892000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X261485404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":29,"alternative-id":["10.1177\/0271678X261485404"],"URL":"https:\/\/doi.org\/10.1177\/0271678x261485404","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"article-number":"0271678X261485404"}}