318 Maternal LPS Enhances Excitotoxic Brain Lesions in Newborn Rats

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Introduction: Epidemiological and experimental data implicate maternal infection in the aetiology of brain white matter injury, which may lead to cerebral palsy in preterm newborns. In newborn rats, intracerebral injection of the glutamatergic analogue iboténate, induces lesions mimicking cystic periventricular leucomalaciaObjective: Our aim was to study the effect of a prenatal maternal treatment with LPS on excitotoxic brain lesions caused by intracerebral injection of ibotenate in rat pups.Methods: Inflammation was caused by Escherichia coli lipopolysaccharide administration to four pregnant rats at days 19 and 20 of gestation (300μg/kg n=2 and 400μg/kg n=2). Two pregnant rats serving as control received a saline injection. Five neonates from each dam were injected intracerebrally with ibotenate at P4 and sacrified at P9 (LPS 300 n=10, LPS 400 n=10 and control n=10). Lesion size was estimated using Cresyl Violet staining. Brain injury was examined on 16μm coronal brain sections.Results: In cortex, we observed a 38% significant increase in lesion size in LPS 300 group compared to controls (p<0.01) and a 61% significant increase in LPS 400 group compared to controls (p<0.01) (LPS 300 group: 832 ± 49.6 μm, LPS 400 group: 966.4 ± 70.4 and Controls: 601.6 ± 38.4). In white matter, we observed a 72% significant increase in lesion size in LPS 300 group compared to controls (p<0.05) and a 137% significant increase in LPS 400 group compared to controls (p<0.001) (LPS 300 group: 505.6 ± 70.4 μm, LPS 400 group: 697.6 ± 70.4 and Controls: 294.4 ± 47.9). We did not find significative difference between LPS 300 and LPS 400 in both cortex and white matter.Conclusions: These results demonstrate that maternal LPS treatment combined with postnatal intracerebral injection of ibotenate enhances excitotoxic brain lesion in pups. Prenatal inflammation seems to play a predisposing role to excitotoxicity induced white matter lesions.