ArticlePloS one2011
Early life stress enhancement of limbic epileptogenesis in adult rats: mechanistic insights.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 80 citations in OpenAlex.
- Stress and HPA axis dysfunction impact diverse epilepsy outcomes including psychiatric comorbidities and SUDEP.Epilepsy research · 2026Review
- Phytocannabinoids restore seizure-induced alterations in emotional behaviour in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Early life stress influences epilepsy outcomes in mice.Epilepsy & behavior : E&B · 2025Article
- Stress and Epilepsy: Towards Understanding of Neurobiological Mechanisms for Better Management.eNeuro · 2023Review
- Antidepressant Drugs for Seizures and Epilepsy: Where do we Stand?Current neuropharmacology · 2023Review
- The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.IBRO neuroscience reports · 2022Review
- Mechanisms of Psychiatric Comorbidities in Epilepsy.Current topics in behavioral neurosciences · 2022Article
- Bidirectional Relations Among Depression, Migraine, and Epilepsy: Do They Have an Impact on Their Response to Treatment?Current topics in behavioral neurosciences · 2022Review
- In Up to My Ears and Temporal Lobes: Effects of Early Life Stress on Epilepsy Development.Current topics in behavioral neurosciences · 2022Article
- The glucocorticoid receptor specific modulator CORT108297 reduces brain pathology following status epilepticus.Experimental neurology · 2021Article
- Article
- Immune Challenges and Seizures: How Do Early Life Insults Influence Epileptogenesis?Frontiers in pharmacology · 2020Review
- The Relationship Between Epilepsy and Anxiety Disorders.Current psychiatry reports · 2019Review
- Affective, neurocognitive and psychosocial disorders associated with traumatic brain injury and post-traumatic epilepsy.Neurobiology of disease · 2019Review
- Size of Subcortical Band Heterotopia Influences the Susceptibility to Hyperthermia-Induced Seizures in a Rat Model.Frontiers in cellular neuroscience · 2019Article
- Bidirectional relations among common psychiatric and neurologic comorbidities and epilepsy: Do they have an impact on the course of the seizure disorder?Epilepsia open · 2018Article
- Common data elements (CDEs) for preclinical epilepsy research: Introduction to CDEs and description of core CDEs. A TASK3 report of the ILAE/AES joint translational task force.Epilepsia open · 2018Article
- Stress and Corticosteroids Aggravate Morphological Changes in the Dentate Gyrus after Early-Life Experimental Febrile Seizures in Mice.Frontiers in endocrinology · 2018Article
- Epilepsy as a Network Disorder (1): What can we learn from other network disorders such as autistic spectrum disorder and mood disorders?Epilepsy & behavior : E&B · 2017Article
- Can Neurochemical Changes of Mood Disorders Explain the Increase Risk of Epilepsy or its Worse Seizure Control?Neurochemical research · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExposure to early postnatal stress is known to hasten the progression of kindling epileptogenesis in adult rats. Despite the significance of this for understanding mesial temporal lobe epilepsy (MTLE) and its associated psychopathology, research findings regarding underlying mechanisms are sparse. Of several possibilities, one important candidate mechanism is early life 'programming' of the hypothalamic-pituitary-adrenal (HPA) axis by postnatal stress. Elevated corticosterone (CORT) in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS would augment seizure-related corticosterone (CORT) release and enhance neuroplastic changes in the hippocampus. METHODOLOGY/PRINCIPAL
findingsEight-week old Wistar rats, previously exposed on postnatal days 2-14 to either maternal separation stress (MS) or control brief early handling (EH), underwent rapid amygdala kindling. We measured seizure-induced serum CORT levels and post-kindling neurogenesis (using BrdU). Three weeks post-kindling, rats were euthanized for histology of the hippocampal CA3c region (pyramidal cell counts) and dentate gyrus (DG) (to count BrdU-labelled cells and measure mossy fibre sprouting). As in our previous studies, rats exposed to MS had accelerated kindling rates in adulthood. Female MS rats had heightened CORT responses during and after kindling (p<0.05), with a similar trend in males. In both sexes total CA3c pyramidal cell numbers were reduced in MS vs. EH rats post-kindling (p = 0.002). Dentate granule cell neurogenesis in female rats was significantly increased post-kindling in MS vs. EH rats. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that early life stress results in enduring enhancement of HPA axis responses to limbic seizures, with increased hippocampal CA3c cell loss and augmented neurogenesis, in a sex-dependent pattern. This implicates important candidate mechanisms through which early life stress may promote vulnerability to limbic epileptogenesis in rats as well as to human MTLE and its associated psychiatric disorders.
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