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Published on: November 20, 2015
Prenatal immune challenge in rats increases susceptibility to seizure-induced brain injury in adulthood
1Pediatric Department of Qilu Hospital, Shandong University, #107 Wenhuaxi Road, Jinan, China.
Insights
Prenatal exposure to inflammation, like from maternal infection, increases seizure susceptibility and brain injury risk in adult offspring. This "two-hit" model shows long-lasting neurodevelopmental effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal infection during pregnancy is linked to neurodevelopmental disorders.
- The impact of prenatal immune activation on adult seizure susceptibility is not fully understood.
Purpose of the Study:
- To investigate if prenatal immune challenge alters susceptibility to seizure-induced brain injury in adult offspring.
- To examine the long-term effects of prenatal inflammation on brain function and injury.
Main Methods:
- Pregnant Wistar rats were exposed to lipopolysaccharide (LPS) or saline during gestation.
- Offspring were assessed for seizure susceptibility using lithium-pilocarpine (LiPC) at adulthood.
- Cognitive function was evaluated using the open field test and Morris water maze.
Main Results:
- Prenatal LPS exposure significantly increased LiPC-induced seizure susceptibility and hippocampal injury in adult offspring.
- The "two-hit" group (prenatal LPS and adult LiPC) exhibited worse performance in behavioral tests compared to controls.
- Prenatal immune activation led to lasting increases in seizure susceptibility and brain vulnerability.
Conclusions:
- Prenatal immune activation establishes a long-term vulnerability to seizures.
- Early-life inflammation can predispose the brain to injury from later seizure events.
- This study highlights the critical role of the prenatal environment in neurodevelopmental outcomes.
Abstract:
Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental injury. Our aim was to investigate whether prenatal immune challenge could alter susceptibility to seizure-induced brain injury in adulthood. Pregnant Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) or normal saline (NS) at days 15 and 16 of gestation. At postnatal day 45, seizure susceptibility was assessed in response to lithium-pilocarpine (LiPC) in adult offspring. Four groups were studied, including normal control (NS-NS), prenatal inflammation (LPS-NS), adult seizure (NS-LiPC), and "two-hit" (LPS-LiPC) groups. Our results demonstrated that adult rat offspring of LPS-exposed dams showed significantly greater susceptibility to LiPC-induced seizures, as well as enhanced hippocampal neuronal injury after seizures. Furthermore, animals in the "two-hit" group performed significantly worse than those from the NS-LiPC group in the open field test and Morris water maze. Our findings suggest that prenatal immune activation can cause a long-lasting increase in seizure susceptibility and predispose the brain to the damaging effect of seizures later in life.
