Lactoferrin for neuroprotection in term neonatal HypoxicIichemic Encephalopathy


Neonatalhypoxia-ischemia (HI) is a leading cause of mortality and chronic disability. Lactoferrin (Lf) isthe major whey protein in milk presenting iron-binding, anti-inflammatory and antiapoptotic properties able to reverse HI brain damage.


Hypothermiais the gold standard for the treatment of TERM babies suffering from HI, however its neuroprotective effects are limited. We hypothesize that the neuroprotection afforded by the oral administration of bovine Lf  can boost therapeutic effects of hypothermia in a rodent model of neonatal HI.

Materials & Methods

Pregnant Wistar rats were fed with bovine Lf supplemented diet (1mg/kg) or control diet from postnatal day 6 (P6). At P7, male and female pup’s had the right common carotid artery occluded followed by hypoxia (8% O2 for 60’) (HI). Immediately after hypoxia, hypothermia (32.5-33.5C for 5h) was performed using Criticool®. Right hippocampus was collected at P8 for mRNA expression assessment. Project approval VD3676.


HI caused major energetic failure and decreases in neurotransmitters not fully reversed by HT nor Lf. Lactate levels and tissue injury were decreased when therapies were combined. Increased mRNA expression of genes related to oxidative stress and neuroinflammation increased by HI were reversed in a greater extent by the combination of Hypothermia and Lactoferrin in the right hippocampus early after brain injury. The additive effects observed in this study point out the need of adjuvant therapies in order to increase the effectiveness of therapeutic hypothermia.

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