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Published on: August 2, 2017
Continuous spike-waves during slow-wave sleep in a mouse model of focal cortical dysplasia
Qian-Quan Sun1, Chen Zhou2, Weiguo Yang2
1Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming, U.S.A. neuron@uwyo.edu.
Objective:
To examine if mice with focal cortical dysplasia (FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography (EEG) features.
Methods:
Unilateral single freeze lesions to the S1 region (SFLS1R) were made in postnatal day 0-1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24-h recordings with intracranial EEG electrodes and behavioral tests were performed in adult SFLS1R and sham-control mice to assess neurologic status.
Results:
A high percentage of adult SFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high-amplitude spike-wave activities and primarily occurring during periods of slow-wave sleep. In comparison, none of the control, age-matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike-waves during slow-wave sleep (CSWS) of the human syndrome described as an electrical status epilepticus during slow-wave sleep (ESES). Key findings in the SFLS1R model indicated that the observed CSWS (1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ-aminobutyric acid (GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike-wave activities.
Significance:
This is the first report of an in vivo animal FCD model that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms of CSWS/ESES.
Insights
Mice with focal cortical dysplasia (FCD) developed spontaneous epileptic seizures, mimicking human continuous spike-waves during slow-wave sleep (CSWS). This new animal model offers insights into CSWS/electrical status epilepticus during slow-wave sleep (ESES) mechanisms.
Area of Science:
- Neuroscience
- Epileptology
- Animal Models
Background:
- Focal cortical dysplasia (FCD) is a developmental brain malformation associated with epilepsy.
- Developing reliable animal models is crucial for understanding FCD-related seizures and developing treatments.
- Spontaneous seizures in FCD models are not well-characterized.
Purpose of the Study:
- To investigate if mice with induced focal cortical dysplasia (FCD) exhibit spontaneous epileptic seizures.
- To identify key electroencephalography (EEG) features of seizures in this FCD model.
- To compare the observed seizure patterns with human epilepsy syndromes.
Main Methods:
- Induction of a neocortical microgyrus in mice via unilateral single freeze lesions at P0-1.
- Continuous 24-hour intracranial EEG recordings and behavioral testing in adult lesioned and sham-control mice.
- Analysis of EEG data for seizure events and comparison with human epilepsy classifications.
Main Results:
- 89% of FCD mice developed spontaneous nonconvulsive seizures, with 60% showing a chronic seizure state.
- Seizure patterns resembled human continuous spike-waves during slow-wave sleep (CSWS)/electrical status epilepticus during slow-wave sleep (ESES).
- Seizures were more prevalent in females, localized to the S1 region but generalized, associated with cognitive deficits, and partially responsive to treatment.
Conclusions:
- This study presents the first in vivo animal model of FCD that generates chronic spontaneous electrographic seizures.
- The model closely mimics human CSWS/ESES, providing a valuable tool for studying these epilepsy types.
- Further research on this model can elucidate the mechanisms underlying abnormal brain oscillations in FCD and related epilepsies.
