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Cells
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Cellular and Molecular Basis of Epilepsy
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Cellular and Molecular Basis of Epilepsy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 6856

Special Issue Editors

Dr. Katarzyna Socała

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Guest Editor
Department of Animal Physiology and Pharmacology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
Interests: seizure; epilepsy; depression; anxiety; behavioral neuroscience; neuropharmacology
Prof. Dr. Piotr Wlaź

E-Mail Website
Guest Editor
Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
Interests: neurobiology, epilepsy; depression; anxiety; behavioral neuroscience; animal models of seizure and epilepsy; antiseizure drugs; pharmacokinetics; drug–drug interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Epilepsy is a heterogeneous group of neurological disorders characterized by recurrent unprovoked seizures, caused by abnormal electrical activity of the whole brain or one of its structures. The etiology of epilepsy is complex and includes structural and metabolic abnormalities, genetic factors, and unknown causes. The mechanism of epileptogenesis, i.e., the process of structural and functional changes transforming the normal brain to one that can generate abnormal neuronal activity, is also multifactorial and unclear. Treatment of epilepsy is still a challenging issue. Pharmacotherapy continues to be the mainstay of epilepsy treatment but about 1/3 of patients remain resistant to the treatment. Moreover, the currently available antiseizure drugs possess only symptomatic activity and they do not suppress epileptogenesis.

This Special Issue will collect original research articles and reviews on the cellular and molecular mechanisms underlying the pathophysiology of seizure, epilepsy and epileptogenesis. Papers on the development of new antiseizure drugs and treatment strategies will be also considered.

Dr. Katarzyna Socała
Prof. Dr. Piotr Wlaź
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • seizure
  • epilepsy
  • epileptogenesis
  • epilepsy models
  • inhibitory/excitatory neurotransmission
  • antiseizure drugs
  • drug discovery

Published Papers (2 papers)

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Research

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35 pages, 3397 KiB  
Article
New Phenylglycinamide Derivatives with Hybrid Structure as Candidates for New Broad-Spectrum Anticonvulsants
by Marcin Jakubiec, Michał Abram, Mirosław Zagaja, Marta Andres-Mach, Aleksandra Szewczyk, Gniewomir Latacz, Bartłomiej Szulczyk, Katarzyna Socała, Dorota Nieoczym, Piotr Wlaź, Cameron S. Metcalf, Karen Wilcox, Rafał M. Kamiński and Krzysztof Kamiński
Cells 2022, 11(12), 1862; https://doi.org/10.3390/cells11121862 - 7 Jun 2022
Cited by 3 | Viewed by 2405
Abstract
In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104, that was previously discovered by our group. Consequently, a series of 22 original compounds has been [...] Read more.
In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104, that was previously discovered by our group. Consequently, a series of 22 original compounds has been designed, synthesized, and characterized in the in vivo and in vitro assays. The obtained compounds showed robust in vivo antiseizure activity in the maximal electroshock (MES) test and in the 6 Hz seizure model (using both 32 and 44 mA current intensities). The most potent compounds 53 and 60 displayed the following pharmacological profile: ED50 = 89.7 mg/kg (MES), ED50 = 29.9 mg/kg (6 Hz, 32 mA), ED50 = 68.0 mg/kg (6 Hz, 44 mA), and ED50 = 73.6 mg/kg (MES), ED50 = 24.6 mg/kg (6 Hz, 32 mA), and ED50 = 56.3 mg/kg (6 Hz, 44 mA), respectively. Additionally, 53 and 60 were effective in the ivPTZ seizure threshold and had no influence on the grip strength and body temperature in mice. The in vitro binding and functional assays indicated a multimodal mechanism of action for 53 and 60. These molecules, beyond TRPV1 antagonism, inhibited calcium currents and fast sodium currents in patch-clamp assays. Further studies proved beneficial in vitro ADME-Tox properties for 53 and 60 (i.e., high metabolic stability, weak influence on CYPs, no neurotoxicity, etc.). Overall, 53 and 60 seem to be interesting candidates for future preclinical development in epilepsy and pain indications due to their interaction with the TRPV1 channel. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis of Epilepsy)
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Review

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50 pages, 4455 KiB  
Review
Animal Models of Drug-Resistant Epilepsy as Tools for Deciphering the Cellular and Molecular Mechanisms of Pharmacoresistance and Discovering More Effective Treatments
by Wolfgang Löscher and H. Steve White
Cells 2023, 12(9), 1233; https://doi.org/10.3390/cells12091233 - 24 Apr 2023
Cited by 18 | Viewed by 3783
Abstract
In the last 30 years, over 20 new anti-seizure medicines (ASMs) have been introduced into the market for the treatment of epilepsy using well-established preclinical seizure and epilepsy models. Despite this success, approximately 20–30% of patients with epilepsy have drug-resistant epilepsy (DRE). The [...] Read more.
In the last 30 years, over 20 new anti-seizure medicines (ASMs) have been introduced into the market for the treatment of epilepsy using well-established preclinical seizure and epilepsy models. Despite this success, approximately 20–30% of patients with epilepsy have drug-resistant epilepsy (DRE). The current approach to ASM discovery for DRE relies largely on drug testing in various preclinical model systems that display varying degrees of ASM drug resistance. In recent years, attempts have been made to include more etiologically relevant models in the preclinical evaluation of a new investigational drug. Such models have played an important role in advancing a greater understanding of DRE at a mechanistic level and for hypothesis testing as new experimental evidence becomes available. This review provides a critical discussion of the pharmacology of models of adult focal epilepsy that allow for the selection of ASM responders and nonresponders and those models that display a pharmacoresistance per se to two or more ASMs. In addition, the pharmacology of animal models of major genetic epilepsies is discussed. Importantly, in addition to testing chemical compounds, several of the models discussed here can be used to evaluate other potential therapies for epilepsy such as neurostimulation, dietary treatments, gene therapy, or cell transplantation. This review also discusses the challenges associated with identifying novel therapies in the absence of a greater understanding of the mechanisms that contribute to DRE. Finally, this review discusses the lessons learned from the profile of the recently approved highly efficacious and broad-spectrum ASM cenobamate. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis of Epilepsy)
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