Maternal Exposure to Lipopolysaccharide Leads to Transient Motor Dysfunction in Neonatal Rats

Abstract

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.

Effects of Maternal Stress during Different Periods of Pregnancy on the Early Neurobehavioral Response of Rats

“…However, maternal deprivation or excitotoxic injury caused by monosodium glutamate treatment led to only transient delay in the development of physical signs, neurological reflexes and motor coordination. Recently, similar results have been found in neonatal inflammation: maternal exposure to lipopolysaccharide leads to transient motor dysfunction in rats [39]. Our present results reveal that rats exposed to prenatal stress showed only subtle positive or negative differences compared to their unstressed mates.…”

A Critical Review of Models of Perinatal Infection

“…Repeated maternal intraperitoneal injection of LPS (0.1 mg/kg) in E15 and E16 pregnant rats was associated with reduced neuronal complexity and spine formation in hippocampal pyramidal neurons [36]. Further, repeated intraperitoneal LPS (0.3 mg/kg) in E19 and E20 pregnant rats resulted in acute neural immune responses with moderate white matter injury and delayed neonatal and adolescent motor performances [37]. …”

Lipopolysaccharide-Induced Preconditioning Attenuates Apoptosis and Differentially Regulates TLR4 and TLR7 Gene Expression after Ischemia in the Preterm Ovine Fetal Brain

“…It is now recognized that the etiology of preterm brain injury is likely multifactorial. While HI is likely to be important, there is now compelling evidence that exposure to infection and secondary inflammation, both before and after birth, is highly associated with preterm brain injury and deficits in neuronal architecture and function in later life [2,3,4,5,6,7,8,9]. …”