Maternal immune activation increases seizure susceptibility in juvenile rat offspring
Ping Yin1, Xin-Ting Zhang1, Jun Li1
1Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
Insights
Maternal infection during pregnancy primes juvenile offspring for increased seizure susceptibility and brain damage. Prenatal immune challenge exacerbates epilepsy-related injuries, impacting learning and memory long-term.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Epidemiological studies link maternal infection to childhood epilepsy.
- Experimental evidence connecting maternal infection to offspring seizure susceptibility is limited.
Purpose of the Study:
- To investigate if maternal immune challenge during pregnancy alters seizure susceptibility and brain damage in juvenile offspring.
- To explore the long-term neurological consequences of prenatal immune activation.
Main Methods:
- Pregnant rats received lipopolysaccharide (LPS) or saline on gestational days 15-16.
- Offspring (postnatal day 21) underwent kainic acid (KA) challenge to assess seizure susceptibility.
- Groups included control, prenatal infection, juvenile seizure, and "two-hit" (prenatal infection + juvenile seizure).
Main Results:
- Maternal LPS exposure induced reactive astrogliosis and heightened seizure susceptibility in juvenile offspring.
- The "two-hit" group exhibited exacerbated astrogliosis and impaired spatial learning compared to the juvenile seizure group.
- Prenatal immune challenge alone impaired spatial learning but did not affect anxiety.
Conclusions:
- Prenatal immune challenge primes astroglia, leading to long-term increases in juvenile seizure susceptibility.
- Maternal infection exacerbates seizure-induced brain injury and cognitive deficits in offspring.
- This study provides experimental evidence for the link between maternal infection and epilepsy risk.
Abstract:
Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia.
