Introduction Lactoferrin (Lf) is an iron-binding glycoprotein secreted in milk with anti-oxydant, anti-inflammatory and anti-microbial properties. The aim of this work was to assess the neuroprotective effect of Lf in P3 rat pup brain exposed to Lypopolysaccharide (LPS) using high-field (9.4 T) ¹H-MR Spectroscopy.

Materials and methods At birth, dams received either a Lf-enriched food (1 g/kg/day) or a diet isocaloric (iso) to the Lf during lactation. Rat pups received Lf through breastfeeding. P3 pups were then divided in 4 groups: sham-iso, LPS-iso, sham-Lf and LPS-Lf (n = 10/group). P3 pups from LPS groups were injected in the subcortical white matter with 0.5 µL saline containing LPS (10 µg) and the sham groups with vehicle. Metabolic profile was measured by ¹H-MRS in the Hippocampus (Hp) and Striatum (St), 24 h (P4) and 21 days (P24) after LPS. A Mann-Whitney test was used to compare values between the different groups (significance: p < 0.05).

Results At 24h, no evidence for ventriculomegaly was observed. At P24 LPS-Iso and LPS-Lf presented significant ventriculomegaly, but ventricle volumes of the LPS-Lf rats (25 ± 2 mm³) tended to be lower than the one of the LPS-Iso group (34 ± 3 mm³) (mean ± SEM) At 24 h, LPS groups (i.e. -Lf and -Iso) exhibited altered metabolism compared to sham groups involving modification of [Glc]-energy source, [Glu+Gln]-neurotransmission and [GPC+PCho]-components of cell membranes. In addition, LPS-Iso group presented also changes in [Mac]-tissue integrity marker, [GABA]-neurotransmitter, [NAA+NAAG]-neuronal marker and [PCr]/[Cr]-energy metabolism compared to sham groups. Interestingly LPS-Iso group presented also differences with the LPS-Lf group: [Mac], [PE]-cell membranes and [Cr+PCr]-energetic metabolism. At P24 the brain metabolism of LPS-exposed rats continued to be disturbed but in a lesser extent for LPS-Lf rats. Further MRI derived data (volumetry and diffusion MRI) are under investigation.

Discussion and conclusion Supplemented in the food during the lactation, Lf appears to have a neuroprotective effect: this result could be of high interest for preterm’s brain neuroprotection.