Optimizing therapeutic hypothermia conditions in a translational preclinical model of neonatal hypoxia-ischemia in rats
Abstract
Background: Therapeutic hypothermia is the only clinically approved treatment for neonatal hypoxia–ischemia (NHI), although its efficacy remains partial. In preclinical research, hypothermia is widely used as a reference therapy; however, its protocol is highly variable across studies, limiting robust comparisons with emerging neuroprotective strategies. This study aimed to define an optimal and standardized hypothermia protocol in the Vannucci model, not to challenge clinical practice, but to establish a reliable benchmark for preclinical therapeutic development. Methods: NHI was induced in postnatal day 7 (P7) rat pups, followed by normothermia or hypothermia for 2, 3, or 5 hours. Short- and long-term outcomes were assessed using lesion volume measurements by MRI, neurological scoring, behavioral tests, and histological analyses. The impact of immediate hypothermia initiation was also examined. Results: Across analyses, both 2- and 3-hour hypothermia durations provided greater neuroprotection than 5 hours—including brain lesion volume, motor and cognitive performances, and markers of neuronal preservation and neuroinflammation. However, for several parameters, 2 hours of hypothermia showed superior efficacy compared with 3 hours. Immediate initiation further modestly improved outcomes. Conclusion: A 2-hour hypothermia protocol represents the most robust and reproducible preclinical reference, enabling meaningful comparison with novel therapies in the Vannucci model.
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BibTeX
@article{ibrahim2026optimizing,
title = {{Optimizing therapeutic hypothermia conditions in a translational preclinical model of neonatal hypoxia-ischemia in rats}},
author = {Ifrah Omar Ibrahim and Pierre Goudeneche and Léonie Dayraut and Stéphane Sanchez and Jean Delmas and Jean-François Chateil and Luc Pellerin and Hélène Roumes and Anne-Karine Bouzier-Sore},
journal = {Pediatric Research},
year = {2026},
month = jun,
doi = {10.1038/s41390-026-05173-3},
url = {https://hal.science/hal-05760043v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Optimizing therapeutic hypothermia conditions in a translational preclinical model of neonatal hypoxia-ischemia in rats
AU - Ifrah Omar Ibrahim
AU - Pierre Goudeneche
AU - Léonie Dayraut
AU - Stéphane Sanchez
AU - Jean Delmas
AU - Jean-François Chateil
AU - Luc Pellerin
AU - Hélène Roumes
AU - Anne-Karine Bouzier-Sore
PY - 2026
DA - 2026/06/30
JO - Pediatric Research
DO - 10.1038/s41390-026-05173-3
UR - https://hal.science/hal-05760043v1
AB - Background: Therapeutic hypothermia is the only clinically approved treatment for neonatal hypoxia–ischemia (NHI), although its efficacy remains partial. In preclinical research, hypothermia is widely used as a reference therapy; however, its protocol is highly variable across studies, limiting robust comparisons with emerging neuroprotective strategies. This study aimed to define an optimal and standardized hypothermia protocol in the Vannucci model, not to challenge clinical practice, but to establish a reliable benchmark for preclinical therapeutic development. Methods: NHI was induced in postnatal day 7 (P7) rat pups, followed by normothermia or hypothermia for 2, 3, or 5 hours. Short- and long-term outcomes were assessed using lesion volume measurements by MRI, neurological scoring, behavioral tests, and histological analyses. The impact of immediate hypothermia initiation was also examined. Results: Across analyses, both 2- and 3-hour hypothermia durations provided greater neuroprotection than 5 hours—including brain lesion volume, motor and cognitive performances, and markers of neuronal preservation and neuroinflammation. However, for several parameters, 2 hours of hypothermia showed superior efficacy compared with 3 hours. Immediate initiation further modestly improved outcomes. Conclusion: A 2-hour hypothermia protocol represents the most robust and reproducible preclinical reference, enabling meaningful comparison with novel therapies in the Vannucci model.
SN - 0031-3998
SN - 1530-0447
ER -