The present study tested a hypothesis that early identification of injury severity with quantitative magnetic resonance imaging (MRI) provides biomarkers for predicting increased seizure susceptibility and epileptogenesis after traumatic brain injury (TBI). TBI was induced by lateral fluid percussion injury (FPI) in adult rats. Quantitative T2, T1ρ, and diffusion were assessed with MRI at 9 days, 23 days, or 2 months post-TBI in the perilesional cortex, thalamus, and hippocampus. Seizure susceptibility was assessed at 12 months after TBI using the pentylenetetrazol seizure-susceptibility test. At 9 and 23 days post-TBI, a change in T1ρ of the perilesional cortex showed the greatest predictive value for increased seizure susceptibility at 12 months post-TBI [area under the curve (AUC), 0.929 and 0.952, respectively; p<0.01]. At 2 months post-TBI, Dav in the thalamus was the best of the biomarkers analyzed (AUC, 0.988; p<0.05). The highest predictive value of all biomarkers was achieved by combining the measurement of Dav in the perilesional cortex and the thalamus at 2 months post-TBI (AUC, 1.000; p<0.01). Our results provide proof-of-concept evidence that clinically relevant MRI biomarkers predict increased seizure susceptibility after experimental TBI.
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http://dx.doi.org/10.1089/neu.2012.2815 | DOI Listing |
Int J Mol Sci
December 2024
Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, 88100 Catanzaro, Italy.
Pathogenic variants are associated with neonatal epilepsies, ranging from self-limited neonatal epilepsy to -developmental and epileptic encephalopathy (DEE). In this study, next-generation sequencing was performed, applying a panel of 142 epilepsy genes on three unrelated individuals and affected family members, showing a wide variability in the epileptic spectrum. The genetic analysis revealed two likely pathogenic missense variants (c.
View Article and Find Full Text PDFJ Physiol
January 2025
Department of Biological Sciences, Southern Methodist University, Dallas, TX, USA.
Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy with possible sex-specific risk factors, although the exact relationship between sex and SUDEP remains unclear. To investigate this, we studied Kcna1 knockout (Kcna1) mice, which lack voltage-gated Kv1.1 channel subunits and are widely used as a SUDEP model that mirrors key features in humans.
View Article and Find Full Text PDFElife
January 2025
Cardiovascular Research Institute, Weill Cornell Medicine, New York City, United States.
Developmental and epileptic encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because is expressed in both excitatory and inhibitory neurons, undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell-type-specific conditional knockout mice.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Background: (absent, small, or homeotic-like 1), a histone methyltransferase, has been identified as a high-risk gene for autism spectrum disorder (ASD). We previously showed that postnatal severe deficiency in the prefrontal cortex (PFC) of male and female mice caused seizures. However, the synaptic mechanisms underlying autism-like social deficits and seizures need to be elucidated.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is a leading cause of mortality and disability worldwide and can lead to secondary sequelae such as increased seizure susceptibility. Emerging work suggests that the thalamus, the relay center of the brain that undergoes secondary damage after cortical TBI, is involved with heightened seizure risks after TBI. TBI also induces the recruitment of peripheral immune cells, including T cells, to the site(s) of injury, but it is unclear how these cells impact neurological sequelae post-TBI.
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