Blood glucose and β-hydroxybutyrate predict significant brain injury after hypoxia-ischemia in neonatal mice.

Journal

Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714

Informations de publication

Date de publication:
24 Aug 2024
Historique:
received: 28 03 2024
accepted: 30 07 2024
revised: 13 07 2024
medline: 26 8 2024
pubmed: 26 8 2024
entrez: 24 8 2024
Statut: aheadofprint

Résumé

The Vannucci procedure is widely used to model cerebral hypoxic-ischemic (HI) injury in neonatal rodents. Identifying minimally invasive biomarkers linked to brain injury would improve stratification of pups to experimental treatments. We hypothesized that extreme blood glucose (BG) and β-hydroxybutyrate (bHB) levels immediately after HI will correlate with severity of brain injury in this model. C57BL6 mice of both sexes underwent the Vannucci procedure with BG and bHB measured immediately after hypoxia. GFAP and α-fodrin were measured to assess injury severity at 4h, P11, P18 and P40. Open field (OF), Y-maze (YM), and Object-location task (OLT) were tested at P40. Clinical seizures-like stereotypies during hypoxia were associated with lower post-hypoxia BG in HI-injured mice. Low BG after HI was related to higher GFAP expression, higher α-fodrin breakdown, lower residual regional volume, and worse working memory. BG was superior to bHB in ROC analysis with BG threshold of <111 mg/dL providing 100% specificity with 72% sensitivity for hippocampal HI-injury. Post-hypoxic BG is a minimally invasive screening tool to identify pups with significant HI brain injury in the Vannucci model modified for mice improving our ability to stratify pups to experimental treatments to assess effectiveness. End hypoxic-ischemic blood glucose levels are a reliable and inexpensive biomarker to detect hypoxic-ischemic brain injury in mice. Screening with blood glucose levels post-hypoxia allows appropriate stratification of those mouse pups most likely to be injured to experimental treatments improving validity and translatability of the results. These findings provide biological plausibility to the clinical observation that extreme blood glucose levels relate to worse outcomes after hypoxia-ischemia.

Sections du résumé

BACKGROUND BACKGROUND
The Vannucci procedure is widely used to model cerebral hypoxic-ischemic (HI) injury in neonatal rodents. Identifying minimally invasive biomarkers linked to brain injury would improve stratification of pups to experimental treatments. We hypothesized that extreme blood glucose (BG) and β-hydroxybutyrate (bHB) levels immediately after HI will correlate with severity of brain injury in this model.
METHODS METHODS
C57BL6 mice of both sexes underwent the Vannucci procedure with BG and bHB measured immediately after hypoxia. GFAP and α-fodrin were measured to assess injury severity at 4h, P11, P18 and P40. Open field (OF), Y-maze (YM), and Object-location task (OLT) were tested at P40.
RESULTS RESULTS
Clinical seizures-like stereotypies during hypoxia were associated with lower post-hypoxia BG in HI-injured mice. Low BG after HI was related to higher GFAP expression, higher α-fodrin breakdown, lower residual regional volume, and worse working memory. BG was superior to bHB in ROC analysis with BG threshold of <111 mg/dL providing 100% specificity with 72% sensitivity for hippocampal HI-injury.
CONCLUSIONS CONCLUSIONS
Post-hypoxic BG is a minimally invasive screening tool to identify pups with significant HI brain injury in the Vannucci model modified for mice improving our ability to stratify pups to experimental treatments to assess effectiveness.
IMPACT CONCLUSIONS
End hypoxic-ischemic blood glucose levels are a reliable and inexpensive biomarker to detect hypoxic-ischemic brain injury in mice. Screening with blood glucose levels post-hypoxia allows appropriate stratification of those mouse pups most likely to be injured to experimental treatments improving validity and translatability of the results. These findings provide biological plausibility to the clinical observation that extreme blood glucose levels relate to worse outcomes after hypoxia-ischemia.

Identifiants

DOI: 10.1038/s41390-024-03461-4 PMID: 39181984
pubmed: 39181984
doi: 10.1038/s41390-024-03461-4
pii: 10.1038/s41390-024-03461-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

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Auteurs

Sarah Ann Duck (SA)

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University - School of Medicine, Baltimore, MD, USA.

Michelle Nazareth (M)

Department of Neuroscience, Johns Hopkins University Krieger School of Arts and Sciences, Baltimore, MD, USA.

Abigail Fassinger (A)

Department of Neuroscience, Johns Hopkins University Krieger School of Arts and Sciences, Baltimore, MD, USA.

Charles Pinto (C)

Department of Human Biology, University of Toronto, Toronto, ON, Canada.

Genesis Elmore (G)

Department of Neuroscience, Johns Hopkins University Krieger School of Arts and Sciences, Baltimore, MD, USA.

Michael Nugent (M)

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University - School of Medicine, Baltimore, MD, USA.

Mark St Pierre (M)

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University - School of Medicine, Baltimore, MD, USA.

Susan J Vannucci (SJ)

Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA.

Raul Chavez-Valdez (R)

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University - School of Medicine, Baltimore, MD, USA. rchavez2@jhmi.edu.
ORCID: 0000-0002-0788-8028

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