From maternal nutrition to neonatal neuroprotection: Passion fruit stilbenes in hypoxia-ischemia.

Abstract

BACKGROUND: Neonatal hypoxia-ischemia (HI) remains a major cause of perinatal morbidity and mortality, leading to lifelong neurological sequelae. Therapeutic hypothermia is the current standard of care but provides only partial protection and must be applied within a narrow therapeutic window. Complementary or preventive neuroprotective strategies are therefore needed. Maternal supplementation with plant-derived polyphenols has shown promising effects in reducing oxidative stress, neuroinflammation, and neuronal loss in experimental models of neonatal HI. Passion fruit extract, rich in stilbenes such as piceatannol, represents a potential neuroprotective candidate, yet its compatibility with post-HI hypothermia has not been systematically evaluated. METHODS: Pregnant rats received oral supplementation with a passion fruit extract of defined polyphenolic composition during the last week of gestation and the first week of lactation. Neonatal HI was induced at postnatal day 7, followed by therapeutic hypothermia (2 h, 32 °C) in selected groups. All experimental groups were compared versus sham (controls) group. Brain injury was assessed using MRI and histology, while behavioral outcomes were evaluated from the neonatal to juvenile period (50 days old). RESULTS: Maternal supplementation with passion fruit extract significantly reduced lesion volumes, attenuated oxidative and inflammatory markers, and improved sensorimotor and cognitive performance. When combined with hypothermia, structural protection was further enhanced, although passion fruit extract alone sometimes provided superior benefit in specific behavioral tests, suggesting possible overlapping or modulatory mechanisms. CONCLUSION: Maternal supplementation with passion fruit extract offers robust neuroprotection against neonatal HI and is compatible with post-HI therapeutic hypothermia. This combined preventive and therapeutic approach may represent a scalable, low-risk, and cost-effective adjunct strategy to enhance outcomes in neonatal HI.