Epilepsy: From Physiopathology to Improvements in Diagnosis and Therapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 8372

Special Issue Editor


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Guest Editor
1. George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
2. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
Interests: neurodegeneration; neuroimmunomodulation

Special Issue Information

Dear Colleagues,

Epilepsy describes a heterogenous group of disorders having in common their tendency to produce seizures. Recent advances in the basic neurosciences provided new insights into the physiopathology of epilepsy. In recent years, revisions of the classification schemata have led to improvements in the recognition of seizure types and diagnosis. New therapeutic options for seizure treatment, including the withdrawal of anticonvulsants from patients who should probably not be treated with these drugs. Surgical management is an increasingly employed therapeutic strategy.

We invite investigators to contribute original research as well as review articles addressing recent advances on aspects regarding epilepsy physiopathology and improvements in its diagnosis. At the same time, research aiming to improve our understanding of the molecular mechanisms of epilepsy treatments is welcome. Original, high-quality contributions that are not yet published or that are not currently under review by other journals or peer-reviewed conferences are welcome

Dr. Clarissa Fantin Cavarsan
Guest Editor

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Keywords

  • epilepsy
  • anticonvulsant
  • epileptic syndrome
  • seizure
  • epileptogenic
  • neuroimmunomodulation

Published Papers (4 papers)

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Research

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22 pages, 5193 KiB  
Article
Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats
by Anastasiya Rebik, Nadezda Broshevitskaya, Syldys Kuzhuget, Pavel Aleksandrov, Kenul Abbasova, Maria Zaichenko and Inna Midzyanovskaya
Biomedicines 2023, 11(9), 2566; https://doi.org/10.3390/biomedicines11092566 - 18 Sep 2023
Cited by 2 | Viewed by 1289
Abstract
Epilepsy or epileptic syndromes affect more than 70 million people, often comorbid with autism spectrum disorders (ASD). Seizures are concerned as a factor for social regression in ASD. A stepwise experimental approach to this problem requires an animal model to provoke seizures and [...] Read more.
Epilepsy or epileptic syndromes affect more than 70 million people, often comorbid with autism spectrum disorders (ASD). Seizures are concerned as a factor for social regression in ASD. A stepwise experimental approach to this problem requires an animal model to provoke seizures and monitor subsequent behavior. We used rats of the Krushinsky–Molodkina (KM) strain as a validated inbred genetic model for human temporal lobe epilepsy, with recently described social deficiency and hypolocomotion. Generalized tonic-clonic seizures in KM rats are sound-triggered, thus being controlled events in drug-naïve animals. We studied whether seizure experience would aggravate contact deficits in these animals. Locomotor and contact parameters were registered in “the elevated plus maze”, “socially enriched open field”, and “social novelty/social preference tests” before and after sound-provoked seizures. The triple seizure provocations minimally affected the contact behavior. The lack of social drive in KM rats was not accompanied by a submissive phenotype, as tested in “the tube dominance test”, but featured with a poor contact repertoire. Here, we confirmed our previous findings on social deficits in KM rats. The contact deficiency was dissociated from hypolocomotion and anxiety and did not correlate with seizure experience. It was established that experience of rare, generalized tonic-clonic convulsions did not lead to an impending regress in contact motivation, as seen in an animal model of genetic epilepsy and comorbid social deficiency. One of the oldest animal models for epilepsy has a translational potential to study mechanisms of social behavioral deficits in future neurophysiological and pharmacological research. Full article
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14 pages, 1223 KiB  
Article
Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus
by Yue Li, S Thameem Dheen, Fengru Tang, Yumin Luo, Ran Meng, Tay Sam Wah Samuel and Lan Zhang
Biomedicines 2022, 10(12), 3012; https://doi.org/10.3390/biomedicines10123012 - 23 Nov 2022
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Abstract
Objective: To investigate microRNA (miRNA) expression profiles before and after pilocarpine-induced status epilepticus (SE) in the cornu ammonis (CA) and dentated gyrus (DG) areas of the mouse hippocampus, and to predict the downstream proteins and related pathways based on bioinformatic analysis. Methods: An [...] Read more.
Objective: To investigate microRNA (miRNA) expression profiles before and after pilocarpine-induced status epilepticus (SE) in the cornu ammonis (CA) and dentated gyrus (DG) areas of the mouse hippocampus, and to predict the downstream proteins and related pathways based on bioinformatic analysis. Methods: An epileptic mouse model was established using a pilocarpine injection. Brain tissues from the CA and DG were collected separately for miRNA analysis. The miRNAs were extracted using a kit, and the expression profiles were generated using the SurePrint G3 Mouse miRNA microarray and validated. The intersecting genes of TargetScan and miRanda were selected to predict the target genes of each miRNA. For gene ontology (GO) studies, the parent-child-intersection (pci) method was used for enrichment analysis, and Benjamini-Hochberg was used for multiple test correction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to detect disease-related pathways among the large list of miRNA-targeted genes. All analyses mentioned above were performed at the time points of control, days 3, 14, and 60 post-SE. Results: Control versus days 3, 14, and 60 post-SE: in the CA area, a total of 131 miRNAs were differentially expressed; 53, 49, and 26 miRNAs were upregulated and 54, 10, and 22 were downregulated, respectively. In the DG area, a total of 171 miRNAs were differentially expressed; furthermore, 36, 32, and 28 miRNAs were upregulated and 78, 58, and 44 were downregulated, respectively. Of these, 92 changed in both the CA and DG, 39 only in the CA, and 79 only in the DG area. The differentially expressed miRNAs target 11–1630 genes. Most of these proteins have multiple functions in epileptogenesis. There were 15 common pathways related to altered miRNAs: nine different pathways in the CA and seven in the DG area. Conclusions: Stage- and subfield-associated hippocampal miRNA expression patterns are closely related to epileptogenesis, although the detailed mechanisms need to be explored in the future. Full article
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21 pages, 4665 KiB  
Article
Acute Hippocampal Damage as a Prognostic Biomarker for Cognitive Decline but Not for Epileptogenesis after Experimental Traumatic Brain Injury
by Eppu Manninen, Karthik Chary, Riccardo De Feo, Elina Hämäläinen, Pedro Andrade, Tomi Paananen, Alejandra Sierra, Jussi Tohka, Olli Gröhn and Asla Pitkänen
Biomedicines 2022, 10(11), 2721; https://doi.org/10.3390/biomedicines10112721 - 27 Oct 2022
Cited by 3 | Viewed by 1390
Abstract
It is necessary to develop reliable biomarkers for epileptogenesis and cognitive impairment after traumatic brain injury when searching for novel antiepileptogenic and cognition-enhancing treatments. We hypothesized that a multiparametric magnetic resonance imaging (MRI) analysis along the septotemporal hippocampal axis could predict the development [...] Read more.
It is necessary to develop reliable biomarkers for epileptogenesis and cognitive impairment after traumatic brain injury when searching for novel antiepileptogenic and cognition-enhancing treatments. We hypothesized that a multiparametric magnetic resonance imaging (MRI) analysis along the septotemporal hippocampal axis could predict the development of post-traumatic epilepsy and cognitive impairment. We performed quantitative T2 and T2* MRIs at 2, 7 and 21 days, and diffusion tensor imaging at 7 and 21 days after lateral fluid-percussion injury in male rats. Morris water maze tests conducted between 35–39 days post-injury were used to diagnose cognitive impairment. One-month-long continuous video-electroencephalography monitoring during the 6th post-injury month was used to diagnose epilepsy. Single-parameter and regularized multiple linear regression models were able to differentiate between sham-operated and brain-injured rats. In the ipsilateral hippocampus, differentiation between the groups was achieved at most septotemporal locations (cross-validated area under the receiver operating characteristic curve (AUC) 1.0, 95% confidence interval 1.0–1.0). In the contralateral hippocampus, the highest differentiation was evident in the septal pole (AUC 0.92, 95% confidence interval 0.82–0.97). Logistic regression analysis of parameters imaged at 3.4 mm from the contralateral hippocampus’s temporal end differentiated between the cognitively impaired rats and normal rats (AUC 0.72, 95% confidence interval 0.55–0.84). Neither single nor multiparametric approaches could identify the rats that would develop post-traumatic epilepsy. Multiparametric MRI analysis of the hippocampus can be used to identify cognitive impairment after an experimental traumatic brain injury. This information can be used to select subjects for preclinical trials of cognition-improving interventions. Full article
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Review

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25 pages, 1188 KiB  
Review
Development of Antiepileptic Drugs throughout History: From Serendipity to Artificial Intelligence
by María Gabriela Corrales-Hernández, Sebastián Kurt Villarroel-Hagemann, Isabella Esther Mendoza-Rodelo, Leonardo Palacios-Sánchez, Mariana Gaviria-Carrillo, Natalia Buitrago-Ricaurte, Santiago Espinosa-Lugo, Carlos-Alberto Calderon-Ospina and Jesús Hernán Rodríguez-Quintana
Biomedicines 2023, 11(6), 1632; https://doi.org/10.3390/biomedicines11061632 - 03 Jun 2023
Cited by 2 | Viewed by 3939
Abstract
This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and [...] Read more.
This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs. Full article
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