319 Maternal LPS Treatment Induces Apoptosis and White Matter Lesions in Newborn Rat Brain

Abstract

Introduction: Periventricular leucomalacia is a white matter lesion characterized by hypomyelination that occurs in preterm human newborn. Maternal inflammation seems to be a major cause of this lesion.Objective: Our aim was to study brain damage after maternal inflammation in newborn rats on P1 and P7.Methods: Inflammation was caused by Escherichia coli lipopolysaccharide administration to pregnant rats at days 19 and 20 of gestation (LPS group, N=8). Control rats got a saline injection (N=8). Neonats were studied at P1 (7 from LPS group, 8 from control) and P7 (8 from LPS group, 7 from control). Myelination was estimated using MBP immunohistochemistry and apoptosis using Terminal transferase assay (TUNNEL) and Caspase-3 immunohistochemistry. Brain injury was examined on 16μm thickness coronal brain sections.Results: At P1, a 114% increase was observed in the number of caspase-3 positive cells in the subventricular striatal zone (40 ± 5 cells per field in the LPS group vs 21 ± 6 in controls, p<0.05). At P7, significant increase of apoptotic cells was found in specific brain areas, i.e. (1) the periventricular striatum (TUNEL: 24 ± 3 cells per field in the LPS group vs 14 ± 2 in controls, p<0.05; Caspase-3: 18 ± 2 vs 8 ± 1, p=0.001), (2) the periventricular white matter (Caspase-3: 12 ± 3 vs 4 ± 1, p<0.05), (3) the germinative ventricular zone: (Caspase-3: 22 ± 4 vs 9 ± 2, p<0.05). At P7, we also observed a strong hypomyelination in 6 out of 8 animals from the LPS group in the external and internal capsules.Conclusions: These results indicate that maternal LPS treatment induces apoptosis associated with strong white matter injury at P7. This model could be relevant for the study of the pathophysiological mechanisms involved in cerebral white matter damage in preterm human newborn.