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Updated: May 6, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Inflammatory response and oxidative stress in developing rat brain and its consequences on motor behavior following
Felipe Stigger1, Gisele Lovatel, Marília Marques
1Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, RS, Brazil; Laboratório de Histofisiologia Comparada, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, RS, Brazil.
Insights
Maternal infection and perinatal anoxia synergistically worsen cerebral palsy outcomes by increasing brain inflammation and oxidative stress in developing pups. This combined insult severely impacts motor development and coordination.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Cerebral palsy (CP) is a motor disorder linked to brain development insults.
- Perinatal asphyxia and maternal infections are associated with increased CP incidence.
Purpose of the Study:
- To investigate the combined effects of maternal lipopolysaccharide (LPS) exposure and perinatal anoxia (PA) on neonatal brain oxidative and inflammatory markers.
- To assess the impact of these insults on neonatal development and motor behavior in offspring.
Main Methods:
- Newborn rats exposed to LPS, PA, or both.
- Measured TNF-α, IL-1, IL-4, SOD, CAT, and DCF in cerebral cortices via ELISA.
- Assessed neonatal developmental milestones and P29 motor behavior (open-field, Rotarod).
Main Results:
- PA alone increased IL-1 but not oxidative stress; LPS alone increased IL-1, TNF-α, free radicals, and SOD activity.
- Combined LPS and PA exposure resulted in greater inflammatory and oxidative stress markers.
- Combined insult led to more significant impairments in development and motor coordination.
Conclusions:
- Prenatal LPS exposure sensitizes the brain to PA, exacerbating neuroinflammation and oxidative damage.
- Synergistic effects of maternal infection and perinatal anoxia contribute to CP-related motor deficits.
- Oxidative and inflammatory pathways in the cerebral cortex are critical in CP development.
Abstract:
Cerebral palsy (CP) is a disorder of locomotion, posture and movement that can be caused by prenatal, perinatal or postnatal insults during brain development. An increased incidence of CP has been correlated to perinatal asphyxia and maternal infections during gestation. The effects of maternal exposure to low doses of bacterial endotoxin (lipopolysaccharide, LPS) associated or not with perinatal anoxia (PA) in oxidative and inflammatory parameters were examined in cerebral cortices of newborns pups. Concentrations of TNF-α, IL-1, IL-4, SOD, CAT and DCF were measured by the ELISA method. Other newborn rats were assessed for neonatal developmental milestones from day 1 to 21. Motor behavior was also tested at P29 using open-field and Rotarod. PA alone only increased IL-1 expression in cerebral cortex with no changes in oxidative measures. PA also induced a slight impact on development and motor performance. LPS alone was not able to delay motor development but resulted in changes in motor activity and coordination with increased levels of IL-1 and TNF-α expression associated with a high production of free radicals and elevated SOD activity. When LPS and PA were combined, changes on inflammatory and oxidative stress parameters were greater. In addition, greater motor development and coordination impairments were observed. Prenatal exposure of pups to LPS appeared to sensitize the developing brain to effects of a subsequent anoxia insult resulting in an increased expression of pro-inflammatory cytokines and increased free radical levels in the cerebral cortex. These outcomes suggest that oxidative and inflammatory parameters in the cerebral cortex are implicated in motor deficits following maternal infection and perinatal anoxia by acting in a synergistic manner during a critical period of development of the nervous system.
