Lactoferrin during lactation protects the immature hypoxic‐ischemic rat brain

Abstract

ObjectiveLactoferrin (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.MethodsModerate 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.ResultsMRI 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.InterpretationLf 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.

A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid β peptide toxicity in Caenorhabditis elegans

“…These data correlate well with previous studies, suggesting that lactoferrin shows neuroprotective effects against brain injury in rats (Van de Looij et al. ) and improves cognition in postnatal piglets through changes in the expression of some genes involved in neurodevelopment and cognition (Chen et al. ).…”

“…These results would support the potential attenuation of the toxicity produced by Aβ(1-42) peptide accumulation in transgenic nematodes, exerted by the LfCD product, and therefore in the delay of body paralysis. These data correlate well with previous studies, suggesting that lactoferrin shows neuroprotective effects against brain injury in rats (Van de Looij et al 2014) and improves cognition in postnatal piglets through changes in the expression of some genes involved in neurodevelopment and cognition (Chen et al 2014).…”

Lactoferrin during lactation reduces lipopolysaccharide‐induced brain injury

“…We showed that prenatal Lf treatment reduces brain impairments in a rat model of stress and intrauterine growth restriction [28]. We also demonstrated a promising neuroprotective effect of postnatal Lf supplementation during lactation period, in a immature rat model (P3) of hypoxic-ischemic brain damage [25].…”

“…Recently we demonstrated that rat pups can receive Lf through breastfeeding from mothers fed with Lf supplemented food [25]. After oral administration, Lf is easily transported to the rodent brain where Lf receptors are expressed in neurons and brain endothelial cells [26,27].…”

Lactoferrin and prematurity: a promising milk protein?

“…Lactoferrin as a nutritional supplement with anti-inflammatory, anti-oxidant and antiapoptotic activities given to the dam from birth and throughout the lactation period showed neuroprotective effect following HI injury in 3 days old rat (P3) (van de Looij et al 2014). Using Advanced Magnetic Resonance Imaging (MRI) analysis, the percentage of injured cortex after HI at P3 as well as the percentage of cortical loss at day 25 (P25) was significantly reduced in the Lf supplemented group, indicating acute and long-term protection effects.…”