Related Experiment Video
Updated: Sep 19, 2025
A Behavioral Screen for Heat-Induced Seizures in Mouse Models of Epilepsy
Published on: July 12, 2021
Gestational hypertension increases risk of seizures in children and mice
Baojian Xue1, Serena B Gumusoglu2,3,4, Grant Tiarks1
1Stead Family Department of Pediatrics.
Insights
Maternal gestational hypertension (GH) increases seizure risk in children. Neuroinflammation may drive this sex-dependent effect, observed in human and mouse studies, highlighting potential in-utero programming.
Area of Science:
- Obstetrics and Gynecology
- Neuroscience
- Developmental Biology
Background:
- Gestational hypertension (GH) affects mothers and in utero-exposed children, posing lifelong health risks.
- Previous research indicates potential links between maternal health conditions and offspring neurological outcomes.
Purpose of the Study:
- To investigate the association between maternal gestational hypertension and seizure risk in offspring.
- To explore the underlying neuroinflammatory mechanisms and sex-specific effects in a mouse model.
Main Methods:
- Analysis of nationwide Epic Cosmos dataset and nested cohorts (Iowa, Stanford, Taiwan) for human data.
- Utilized an angiotensin II-induced mouse model of GH to study offspring seizure susceptibility.
- Examined gene expression, microglial involvement, and effects of anti-inflammatory treatments in offspring.
Main Results:
- Children of mothers with GH exhibited significantly higher seizure rates across multiple human cohorts.
- Maternal Angiotensin II infusion in mice led to increased seizure susceptibility and mortality in male offspring, with broader effects under electrical stimulation.
- Neuroinflammation and microglial activation were elevated in male offspring; anti-inflammatory interventions mitigated seizure risk.
Conclusions:
- Gestational hypertension is associated with an increased risk of seizures in offspring, suggesting in utero programming.
- Neuroinflammatory pathways, potentially sex-dependent, may mediate the heightened seizure susceptibility observed in offspring exposed to GH in utero.
- These findings underscore the importance of managing GH for long-term offspring neurological health.
Abstract:
Gestational hypertension (GH) is prevalent, with life-long health burdens for mothers and their children exposed in utero. We analyzed the nation-wide Epic Cosmos dataset and found significantly higher rates of seizures in children of mothers with GH than in children of normotensive mothers. Complementary studies of nested Iowa and Stanford cohorts and a large Taiwanese cohort also revealed significantly increased seizure risk after covariate adjustments. We modeled this association in an angiotensin (ANG) II mouse model of GH. Maternal ANG II significantly increased seizure grade and deaths elicited by pilocarpine among male but not female offspring. Electrical stimulation increased seizure grade and death across sexes in offspring from ANG II-treated dams. Proinflammatory and microglial gene expression in the brain were upregulated only in male offspring from ANG II-treated dams. Chronic phenylephrine, a GH model lacking the maternal proinflammatory aspects of ANG II, induced similar offspring seizure phenotypes. PLX5622-induced depletion of microglia or antiinflammatory pentoxifylline abolished this sensitized seizure response and lowered mortality in the ANG II model. These results suggest that GH programs offspring risk for seizures in a sex-dependent manner in humans and mice. Neuroinflammatory mechanisms may contribute to the elevated sensitivity and mortality from seizures elicited by GH exposure in utero.
More Related Videos
Related Concept Videos
01:24Epilepsy and Seizures: Overview
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
01:07Teratogenicity