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Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia\/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100\u2009mg\/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-\u03b1. Moreover, using UPLC-MS\/MS we found that maternal supplementation with Ole during pregnancy and\/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. 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