期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 41, 期 2, 页码 342-358出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X20908355
关键词
Neonatal hypoxia-ischemia; lactate; neuroprotection; astrocyte to neuron lactate shuttle; MRI
资金
- TRAIL (Translational Research and Advanced Imaging Laboratory) cluster of excellence of Bordeaux University
- program IdEx
- LabEx TRAIL [ANR-10-IDEX, ANR-10-LABX-57]
- international French (ANR)/Swiss (FNS) [ANR-15-CE37-0012]
- FNS [310030E164271]
- program IdEx Bordeaux [ANR-10-IDEX-03-02]
Lactate has shown neuroprotective effects in a neonatal hypoxia-ischemia model, reducing brain lesion volume rapidly and efficiently. Lactate metabolism plays a key role in this protection, and lactate administration holds promise as an effective therapy for neonatal HI insult.
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 mu mol). 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.
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