{
  "abstract": "Background and Purpose: Neonatal hypoxia-ischemia (NHI) is a leading cause of mortality and long-term neurodevelopmental disability. Therapeutic hypothermia (TH) is currently the only established treatment for NHI; however, its efficacy remains limited, underscoring the need for adjunctive neuroprotective strategies. Lactate is now regarded as a major metabolic substrate of the brain and has previously been shown to exert neuroprotective effects following experimental NHI. We investigated whether lactate enhances hypothermia-induced neuroprotection and evaluated the optimal timing of administration and potential underlying mechanisms. Methods: Postnatal day 7 Wistar rats were subjected to NHI using the Rice-Vannucci model and treated with TH alone (2h at 32°C), sodium L-lactate alone, or combined L-lactate–TH. Animals underwent longitudinal magnetic resonance imaging (MRI) and behavioral assessments, complemented by histological, immunohistochemical, and Western blot analyses, including assessment of protein lactylation. The effect of sodium L-lactate administration timing relative to TH was also evaluated. Results: Lactate significantly enhanced the neuroprotective effects of TH, particularly when administered before hypothermia, resulting in greater lesion recovery, reduced neuroinflammation and apoptotic cell death, preserved neuronal integrity, and improved long-term motor and cognitive outcomes. Combined treatment preserved neuronal lactate transporter, prevented NHI-induced astrocytic glutamate transporter upregulation, modulated lactylation markers, supporting coordinated metabolic and epigenetic adaptations following NHI. Conclusions: Early lactate administration enhances the neuroprotective efficacy of TH following NHI. These findings identify lactate as a promising adjunct to TH and support its translational potential as a metabolic strategy to improve outcomes following NHI brain injury.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Ifrah Omar Ibrahim"
    },
    {
      "name": "Sébastien Giraud"
    },
    {
      "name": "Estelle Lemarié"
    },
    {
      "name": "Anne-Karine Bouzier-Sore"
    },
    {
      "name": "Marie-Christine Beauvieux"
    },
    {
      "name": "Stéphane Sanchez"
    },
    {
      "name": "Marc Biran"
    },
    {
      "name": "Aurélien Trottier"
    },
    {
      "name": "Karine Viaud"
    },
    {
      "name": "Jean-François Chateil"
    },
    {
      "name": "Jean Delmas"
    },
    {
      "name": "Luc Pellerin"
    },
    {
      "name": "Hélène Roumes"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/529pk37h86y7q.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754268",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754268v1.full",
  "id": "529pk37h86y7q",
  "issns": [],
  "landing_url": "https://hal.science/hal-05795436v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2735|Neonatal and fetal brain pathology"
    ]
  ],
  "openalex": "W7215130847",
  "pdf_url": "https://hal.science/hal-05795436/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/529pk37h86y7q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:55Z",
      "native_id": "hal-05795436",
      "source": "hal",
      "url": "https://hal.science/hal-05795436v1"
    },
    {
      "first_seen": "2026-10-30T12:25:37Z",
      "native_id": "10.64898/2026.09.24.754268",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754268v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Combined lactate and hypothermia therapy enhances neuroprotection following neonatal hypoxic-ischemic brain injury",
  "title_text": "Combined lactate and hypothermia therapy enhances neuroprotection following neonatal hypoxic-ischemic brain injury",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:37Z",
  "url": "https://research.draconitic.com/paper/529pk37h86y7q",
  "venue": "HAL",
  "versions": []
}