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Updated: Mar 13, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in
Yi Pang1, Xuemei Dai1, Anna Roller2
1Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
Insights
Early-life inflammation from lipopolysaccharide (LPS) alters microglia phenotypes, impacting neural development and causing cognitive deficits. M2-like microglia activation may contribute to autism spectrum disorder (ASD)-like behaviors.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Perinatal infections are linked to neurodevelopmental disorders like white matter injury (WMI) and autism spectrum disorders (ASD).
- Mechanisms connecting early inflammation to aberrant neural development are not fully understood.
Purpose of the Study:
- To investigate the effects of lipopolysaccharide (LPS)-induced neuroinflammation on microglia phenotypes and early neural development in rats.
- To explore the relationship between microglial activation, neural development, and behavioral outcomes.
Main Methods:
- Rats were exposed to LPS on postnatal day 3 to induce systemic neuroinflammation.
- Microglia phenotypes (M1/M2), apoptosis, cell proliferation, and oligodendrocyte lineage populations were assessed.
- Communicative and cognitive functions were evaluated in LPS-exposed rats.
Main Results:
- LPS exposure induced mixed M1 and M2 microglial activation, with M2 markers strongly upregulated in specific brain regions.
- A decrease in apoptosis and an increase in cell proliferation were observed in the subventricular zone and dentate gyrus.
- LPS-exposed rats showed increased oligodendrocyte lineage cells and significant impairments in communicative and cognitive functions.
Conclusions:
- M2-like microglial activation may play a role in abnormal neural development following early-life inflammation.
- These neurodevelopmental alterations could underlie autism spectrum disorder (ASD)-like behavioral impairments.
Abstract:
Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI) and Autism Spectrum Disorders (ASD). The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS)-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats. We show here that LPS exposure at early postnatal day 3 leads to a robust microglia activation which is characterized with mixed microglial proinflammatory (M1) and anti-inflammatory (M2) phenotypes. More specifically, we found that microglial M1 markers iNOS and MHC-II were induced at relatively low levels in a regionally restricted manner, whereas M2 markers CD206 and TGFβ were strongly upregulated in a sub-set of activated microglia in multiple white and gray matter structures. This unique microglial response was associated with a marked decrease in naturally occurring apoptosis, but an increase in cell proliferation in the subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus. LPS exposure also leads to a significant increase in oligodendrocyte lineage population without causing discernible hypermyelination. Moreover, LPS-exposed rats exhibited significant impairments in communicative and cognitive functions. These findings suggest a possible role of M2-like microglial activation in abnormal neural development that may underlie ASD-like behavioral impairments.
