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.