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Objective  Lactoferrin (Lf) is an iron‐binding glycoprotein secreted in maternal milk presenting anti‐inflammatory and antioxidant properties. It shows efficient absorption into the brain from nutritional source. Brain injury frequently resulting from cerebral hypoxia‐ischemia ( HI ) has a high incidence in premature infants with ensuing neurodevelopmental disabilities. We investigated the neuroprotective effect of maternal nutritional supplementation with Lf during lactation in a rat model of preterm  HI  brain injury using magnetic resonance imaging ( MRI ), brain gene, and protein expression.    Methods  Moderate brain  HI  was induced using unilateral common carotid artery occlusion combined with hypoxia (6%, 30 min) in the postnatal day 3 (P3) rat brain (24–28 weeks human equivalent). High‐field multimodal  MRI  techniques were used to investigate the effect of maternal Lf supplementation through lactation. Expression of cytokine coding genes ( TNF ‐ α  and  IL ‐6), the prosurvival/antiapoptotic  AKT  protein and caspase‐3 activation were also analyzed in the acute phase after  HI .    Results   MRI  analysis demonstrated reduced cortical injury in Lf rats few hours post‐ HI  and in long‐term outcome (P25). Lf reduced  HI ‐induced modifications of the cortical metabolism and altered white matter microstructure was recovered in Lf‐supplemented rats at P25. Lf supplementation significantly decreased brain  TNF ‐ α  and  IL ‐6 gene transcription, increased phosphorylated  AKT  levels and reduced activation of caspase‐3 at 24 h post‐injury.    Interpretation  Lf given through lactation to rat pups with cerebral  HI  injury shows neuroprotective effects on brain metabolism, and cerebral gray and white matter recovery. This nutritional intervention may be of high interest for the clinical field of preterm brain neuroprotection.

Lactoferrin during lactation protects the immature hypoxic‐ischemic rat brain