Maternal exposure to lipopolysaccharide leads to transient motor dysfunction in neonatal rats

Epidemiological and experimental data implicate maternal infection and inflammation in the etiology of brain white matter injury, which may lead to cerebral palsy in preterm newborns. Our aim was to investigate motor development of the offspring after maternal administration of lipopolysaccharide (LPS). Wistar rats were intraperitoneally injected with Escherichia coli LPS or saline on gestational days 19 and 20. From birth to 3 weeks, pups were tested for neurobehavioral development, neurological signs and reflexes. From 3 to 6 weeks, motor coordination was investigated. At 4 months, animals were tested for locomotion. Brain myelination was assessed by myelin basic protein immunohistochemistry. Days of appearance of several neurological reflexes were significantly delayed, and neonate LPS pups displayed retarded performance in righting, gait and negative geotaxis. At the juvenile stage, LPS animals showed important impairment in coordination. However, although the LPS group performed worse in most tests, they reached vehicle levels by 5 weeks. At 4 months, LPS animals did not show variations in locomotion performances compared to vehicle. No myelination differences have been observed in the brains at adulthood. Maternal LPS administration results in delayed motor development even though these alterations fade to reach control level by 5 weeks. Motor impairments observed at the early stage in this study could be linked to previously reported hypomyelination of the white matter induced by maternal LPS challenge in the neonates. Finally, the normal myelination shown here at adulthood may explain the functional recovery of the animals and suggest either a potential remyelination of the brain or a delayed myelination in LPS pups.