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Updated: Dec 25, 2025
Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy
Published on: October 28, 2022
Neuroprotective role of lactate in rat neonatal hypoxia-ischemia
Hélène Roumes1, Ursule Dumont1, Stéphane Sanchez1
1Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536, CNRS/Université de Bordeaux, Bordeaux Cedex, France.
Insights
Lactate shows neuroprotective effects against brain injury in newborn rats with hypoxic-ischemic encephalopathy. This promising therapy significantly reduces brain lesions and improves neurological function.
Area of Science:
- Neuroscience
- Biochemistry
- Neonatal Medicine
Background:
- Hypoxic-ischemic (HI) encephalopathy is a leading cause of newborn mortality and disability.
- Current hypothermia treatment is effective in less than 60% of cases.
- Lactate is recognized as a neuronal fuel and signaling molecule.
Purpose of the Study:
- To investigate the neuroprotective potential of lactate in a neonatal rat model of HI.
- To assess the impact of lactate administration on brain lesion volume and neurological recovery.
Main Methods:
- Neonatal rats (seven days old) were subjected to a hypoxia-ischemia model.
- Lactate was administered via intra-peritoneal injection.
- Magnetic resonance diffusion-weighted imaging, oxiblot analyses, and behavioral studies were performed.
Main Results:
- A single lactate injection reduced brain lesion volume by 30%.
- Co-injection with oxamate (lactate dehydrogenase inhibitor) abolished neuroprotection, indicating lactate metabolism is crucial.
- Multiple lactate injections led to minimal brain lesions and full recovery of neurological functions.
Conclusions:
- Lactate exhibits rapid and efficient neuroprotective effects in neonatal HI encephalopathy.
- Lactate metabolism plays a key role in its neuroprotective mechanism.
- Lactate administration represents a promising therapeutic strategy for neonatal HI insult.
Abstract:
Hypoxic-ischemic (HI) encephalopathy remains a major cause of perinatal mortality and chronic disability in newborns worldwide (1-6 for 1000 births). The only current clinical treatment is hypothermia, which is efficient for less than 60% of babies. Mainly considered as a waste product in the past, lactate, in addition to glucose, is increasingly admitted as a supplementary fuel for neurons and, more recently, as a signaling molecule in the brain. Our aim was to investigate the neuroprotective effect of lactate in a neonatal (seven day old) rat model of hypoxia-ischemia. Pups received intra-peritoneal injection(s) of lactate (40 μmol). Size and apparent diffusion coefficients of brain lesions were assessed by magnetic resonance diffusion-weighted imaging. Oxiblot analyses and long-term behavioral studies were also conducted. A single lactate injection induced a 30% reduction in brain lesion volume, indicating a rapid and efficient neuroprotective effect. When oxamate, a lactate dehydrogenase inhibitor, was co-injected with lactate, the neuroprotection was completely abolished, highlighting the role of lactate metabolism in this protection. After three lactate injections (one per day), pups presented the smallest brain lesion volume and a complete recovery of neurological reflexes, sensorimotor capacities and long-term memory, demonstrating that lactate administration is a promising therapy for neonatal HI insult.
