Review
Clinical Neurology
Jing You, Haiyan Huang, Clement T. Y. Chan, Lin Li
Summary: This review article summarizes the latest neuropathological discoveries at the molecular, cellular, and tissue levels involving both animal and patient studies, aiming to explore epileptogenesis and highlight new potential targets in the diagnosis and treatment of TLE.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Mani Ratnesh S. Sandhu, Benjamin F. Gruenbaum, Shaun E. Gruenbaum, Roni Dhaher, Ketaki Deshpande, Melissa C. Funaro, Tih-Shih W. Lee, Hitten P. Zaveri, Tore Eid
Summary: Glutamine synthetase (GS) in astrocytes plays a crucial role in epilepsy, with deficiency or dysfunction linked to various types of seizures. Experimental studies have shown that inhibition or deletion of GS in animals can lead to a syndrome resembling mesial temporal lobe epilepsy.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Ceng-Lin Xu, Jia-Zhen Nao, Yu-Jia Shen, Yi-Wei Gong, Bei Tan, Shuo Zhang, Ke-Xin Shen, Cui-Rong Sun, Yi Wang, Zhong Chen
Summary: By applying different regimens of music therapy in various temporal lobe epilepsy models, it was determined that long-term full-length Mozart K.448 could enhance the anti-seizure efficacy of sub-dose drugs. These results suggest that long-term full-length Mozart K.448 may be a promising noninvasive adjuvant therapy for temporal lobe epilepsy.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Review
Clinical Neurology
Dandan Zhang, Siyuan Chen, Shoucheng Xu, Jing Wu, Yuansu Zhuang, Wei Cao, Xiaopeng Chen, Xuezhong Li
Summary: Alzheimer's disease and epilepsy are common neurological disorders in older adults, and there is a bidirectional association between them. Epilepsy is a risk factor for Alzheimer's disease, while Alzheimer's disease is an independent risk factor for epilepsy in old age.
FRONTIERS IN NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kristina D. Yakovleva, Diana V. Dmitrenko, Iulia S. Panina, Anna A. Usoltseva, Kirill A. Gazenkampf, Olga V. Konovalenko, Elena A. Kantimirova, Maxim A. Novitsky, Regina F. Nasyrova, Natalia A. Shnayder
Summary: This article systematically analyzes the role of miRs in the development of mesial TLE (mTLE) and provides an update on the existing knowledge about the biomarkers of this disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
Alessia Longo, Marion Houot, Bastien Herlin, Marie Mere, Marisa Denos, Severine Samson, Sophie Dupont
Summary: The study found that the localization of the epileptic focus within the lateral temporal lobe affects the neuropsychological characteristics of patients with LTLE, resulting in differences in learning, executive performance, and language difficulties. Antiepileptic drugs have a greater impact on patient performance, while age, education level, and gender also influence cognitive performance.
EPILEPSY & BEHAVIOR
(2021)
Review
Pharmacology & Pharmacy
Krzysztof Lukawski, Stanislaw J. Czuczwar
Summary: This article discusses novel drug targets for the management of drug-resistant seizures, including brain multidrug efflux transporters and inflammatory pathways. Strategies for reducing blood brain barrier dysfunction and enhancing anti-oxidative defense are also explored.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Neurosciences
Amanda Larissa Dias Pacheco, Igor Santana de Melo, Maisa de Araujo Costa, Mariah Morais Celestino Amaral, Nivea Karla de Gusmao Taveiros Silva, Yngrid Mickaelli Oliveira Santos, Daniel Leite Goes Gitai, Marcelo Duzzioni, Alexandre Urban Borbely, Robinson Sabino Silva, Ana Luiza Ferreira Donatti, Luisa Mestriner, Carlos Alessandro Fuzo, Richard D. Cummings, Norberto Garcia-Cairasco, Marcelo Dias-Baruffi, Olagide Wagner de Castro
Summary: Administration of GAL-1 reduces the severity of seizures, inflammation, and neurodegeneration, suggesting a neuroprotective effect in the early stage of epileptogenesis.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Sonali Kumar, Diksha Attrish, Arpna Srivastava, Jyotirmoy Banerjee, Manjari Tripathi, P. Sarat Chandra, Aparna Banerjee Dixit
Summary: The review explores the role of HDACs in epilepsy, focusing on their action on non-histone substrates and the potential of HDACi as anti-epileptic drugs. It also discusses the importance of identifying novel targets of HDACs for more effective anti-epileptogenic therapy.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Review
Biochemistry & Molecular Biology
Marek J. Pawlik, Barbara Miziak, Aleksandra Walczak, Agnieszka Konarzewska, Magdalena Chroscinska-Krawczyk, Jan Albrecht, Stanislaw J. Czuczwar
Summary: Epileptogenesis is the process of converting a normal brain into an epileptic one, with only a few antiepileptic drugs showing potential in preventing this transformation. Limited clinical data suggest certain non-antiepileptic drugs may have antiepileptogenic potential, and further research on reliable markers of early epileptogenesis is needed for designing adequate antiepileptogenic therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Andreia Gomes-Duarte, Sebastian Bauer, Morten T. Veno, Braxton A. Norwood, David C. Henshall, Jorgen Kjems, Felix Rosenow, Vamshidhar R. Vangoor, R. Jeroen Pasterkamp
Summary: The study investigated the regulation of circRNAs during the development of epilepsy and revealed an intriguing link between circRNA deregulation and the transition of brain networks into the state of spontaneous seizure activity. These findings provide a molecular framework for further understanding the role and mechanism-of-action of circRNAs in TLE.
FRONTIERS IN GENETICS
(2021)
Article
Neurosciences
Doodipala Samba Reddy, Robert H. Mbilinyi, Sreevidhya Ramakrishnan
Summary: At present, there is no drug therapy available for curing epilepsy. However, recent research has shown the potential of cannabidiol (CBD) in controlling epileptogenesis and reducing seizure burden. CBD can also be used in combination with other antiseizure medications, indicating strong potential as an adjunct therapy.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Anna Maria Costa, Mohammad Gol, Chiara Lucchi, Giuseppe Biagini
Summary: This study found that increasing the levels of the anticonvulsant neurosteroid allopregnanolone may delay the development of epileptic seizures. By using the inhibitor trilostane to increase allopregnanolone levels, researchers observed a delay in seizure onset in rats. These findings have important implications for the development of new treatment methods.
Article
Medicine, General & Internal
Rod W. Hunt, Helen G. Liley, Deepika Wagh, Rachel Schembri, Katherine J. Lee, Andrew D. Shearman, Samantha Francis-Pester, Koert DeWaal, Jeanie Y. L. Cheong, Monika Olischar, Nadia Badawi, Flora Y. Wong, David A. Osborn, Victor Samuel Rajadurai, Peter A. Dargaville, Bevan Headley, Ian Wright, Paul B. Colditz
Summary: This randomized clinical trial aimed to determine whether active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improved survival free of severe disability at 2 years compared with only treating clinically detected seizures. The study found that treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures. Additionally, there was evidence that cognitive outcomes were worse in the group where both types of seizures were actively managed.
Article
Neurosciences
Maxime Levesque, Siyan Wang, Anezka D. B. Macey-Dare, Pariya Salami, Massimo Avoli
Summary: Interictal activity, recorded with cortical and intracerebral EEG recordings, is heterogeneous in its patterns and can indicate the epileptogenic processes occurring in focal epileptic disorders in animal models and, perhaps, in epileptic patients. However, its relationship with seizures is still debated. Moreover, it is unclear whether specific EEG changes in interictal activity occur during the latent period preceding the appearance of spontaneous seizures.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Massimo Pierucci, Francis Delicata, Roberto Colangeli, Antonella Marino Gammazza, Alessandro Pitruzzella, Maurizio Casarrubea, Philippe De Deurwaerdere, Giuseppe Di Giovanni
Summary: This study found that nicotine-induced neuronal activity in the VTA is regulated by the LHb region, with acute and chronic nicotine having different effects on VTA DA neurons.
Review
Biochemistry & Molecular Biology
Abdeslam Chagraoui, Giuseppe Di Giovanni, Philippe De Deurwaerdere
Summary: The discovery of the D3 receptor has sparked interest in the field of neurological diseases, particularly Parkinson's disease. This article discusses the role of D3 receptors in Parkinson's disease and their relationship with current treatments, highlighting the potential interactions between D1 and D3 receptors that may contribute to motor side effects.
Article
Biochemistry & Molecular Biology
An Buckinx, Dimitri De Bundel, Ron Kooijman, Ilse Smolders
Summary: Epilepsy is a neurological disease that affects over 50 million individuals worldwide. Despite the availability of various drugs for treatment, 30% of patients still suffer from pharmacoresistant epilepsy. Ghrelin receptor (ghrelin-R) has emerged as a promising new therapeutic target with anticonvulsant effects.
Article
Biochemistry & Molecular Biology
Najat Aourz, Fred Van Leuven, Wissal Allaoui, Ann Van Eeckhaut, Dimitri De Bundel, Ilse Smolders
Summary: Two isoforms of glycogen synthase kinase-3 (GSK-3), GSK-3 alpha and GSK-3 beta, have been identified in mammals. This study investigates the role of GSK-3 beta in seizures and its potential as a drug target for pharmacoresistant seizures. The results suggest that GSK-3 beta inhibition has anticonvulsant effects, but sustained disruption of GSK-3 beta activity may contribute to kindling in the long term.
ACS CHEMICAL NEUROSCIENCE
(2022)
Letter
Neurosciences
Daniel Cassar, Manuela Radic, Maurizio Casarrubea, Vincenzo Crunelli, Giuseppe Di Giovanni
Summary: In this study, GAERS and NEC rats were treated with the CB1/2 receptor agonist WIN 55,212-2 (2 mg/kg) and tested on the Elevated Plus-Maze.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Marie-Laure Custers, Liam Nestor, Dimitri De Bundel, Ann Van Eeckhaut, Ilse Smolders
Summary: This review discusses the applicability of microdialysis and other techniques for monitoring macromolecules in the brain, which is challenging due to the limited techniques available for direct sampling from the cerebral interstitial space. The review also addresses innovations, pitfalls, and research gaps in these techniques. Implementing these techniques can help improve drug development for brain-targeted drugs.
Article
Oncology
Hatice Satilmis, Emma Verheye, Philip Vlummens, Inge Oudaert, Niels Vandewalle, Rong Fan, Jennifer M. Knight, Nathan De Beule, Gamze Ates, Ann Massie, Jerome Moreaux, Anke Maes, Elke De Bruyne, Karin Vanderkerken, Eline Menu, Erica K. Sloan, Kim De Veirman
Summary: This study investigates the potential therapeutic effects of beta-blockers, specifically targeting the beta(2)-adrenergic receptor, in multiple myeloma treatment. The blockade of beta(2)-adrenergic receptors reduces cell viability, induces apoptosis and autophagy, and modulates cancer cell metabolism. Combining beta(2)AR blockade with other drugs enhances apoptosis in multiple myeloma cells.
JOURNAL OF PATHOLOGY
(2023)
Article
Clinical Neurology
Marie-Laure Custers, Maxime Vande Vyver, Lea Kaltenbock, Kurt Barbe, Maria Bjerke, Ann Van Eeckhaut, Ilse Smolders
Summary: In the management of epilepsy, the discovery of new biomarkers is important for improving diagnosis, monitoring disease progression, and evaluating treatment responsiveness. This study investigates the potential of neurofilament light chain (NfL) as a diagnostic and response fluid biomarker for epilepsy.
Review
Neurosciences
Jo Bossuyt, Yana Van Den Herrewegen, Liam Nestor, An Buckinx, Dimitri De Bundel, Ilse Smolders
Summary: Insights into the roles of astrocytes and microglia in normal and diseased brain functioning have been greatly expanded in recent years, thanks to the emergence of chemogenetic tools. These cutting-edge techniques enable precise manipulation of specific glial cell types, leading to significant advances in our understanding of how glial cells contribute to various central nervous system functions and diseases. This article discusses the latest findings in glial cell functions using chemogenetics, focusing on the manipulation of intracellular signaling pathways in astrocytes and microglia induced by designer receptors exclusively activated by designer drugs (DREADDs). The potential limitations and translational prospects of this technology are also explored.
Article
Oncology
Arne Van der Vreken, Inge Oudaert, Gamze Ates, Sylvia Faict, Philip Vlummens, Hatice Satilmis, Rong Fan, Anke Maes, Ann Massie, Kim De Veirman, Elke De Bruyne, Karin Vanderkerken, Eline Menu
Summary: This study suggests an alternative combination treatment for multiple myeloma by targeting metabolic pathways. The combination of syrosingopine and metformin shows strong cytotoxic effects on multiple myeloma cell lines and patient samples, suppressing both glycolysis and oxidative phosphorylation. Furthermore, the combination treatment leads to a significant reduction in tumor burden in vivo.
JOURNAL OF PATHOLOGY
(2023)
Article
Chemistry, Analytical
Jana Bongaerts, Dimitri De Bundel, Ilse Smolders, Debby Mangelings, Yvan Vander Heyden, Ann Van Eeckhaut
Summary: Neuromedin U (NmU) and neuromedin S (NmS) are neuropeptides belonging to the neuro-medin family. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the preferred analytical technique for peptide quantification, but quantification limits for these peptides in biological samples remain challenging due to nonspecific binding. This study focuses on solving the adsorption problem and improving the sensitivity of the LC-MS/MS method for NmU and NmS.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Mireia Medrano, Wissal Allaoui, Mathias Van Bulck, Sofie Thys, Leila Makrini-Maleville, Eve Seuntjens, Winnok H. De Vos, Emmanuel Valjent, Balazs Gaszner, Ann Van Eeckhaut, Ilse Smolders, Dimitri De Bundel
Summary: Neuromedin U (NMU) is an evolutionarily conserved neuropeptide that plays a role in various processes. A knock-in mouse model expressing Cre recombinase under the Nmu promoter has been generated, allowing a comprehensive characterization of NMU-expressing neurons in the brain. The model has been validated using multiple approaches, and the results suggest that it is a powerful and sensitive tool for studying the role of NMU neurons in mice.
Article
Neurosciences
Maurizio Casarrubea, Manuela Radic, Tatiana Pinto Morais, Erika Mifsud, Eleonora Cuboni, Stefania Aiello, Giuseppe Crescimanno, Vincenzo Crunelli, Giuseppe Di Giovanni
Summary: The study compared Genetic Absence Epilepsy Rats from Strasbourg (GAERS), non-epileptic control (NEC), and Wistar rats bred under the same conditions, along with commercially available Wistar rats (Cm Wistar) as a control. The results showed that male GAERS rats lacked comorbid anxiety, and the study emphasized the importance of using Wistar rats from the same breeding conditions.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Geriatrics & Gerontology
Maxime Vande Vyver, Louise Daeninck, Gino De Smet, Najat Aourz, Surajit Sahu, Sebastiaan Engelborghs, Kris Pauwels, Dimitri De Bundel, Ilse Smolders
Summary: We investigated the impact of A beta(1-42) oligomers on seizure susceptibility in mice and found no effect after intracerebral injection. Despite confirming the presence of A beta(1-42) oligomers, it remains unclear whether our findings or previous studies best represent the role of these oligomers in seizures in AD.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Oncology
Rong Fan, Hatice Satilmis, Niels Vandewalle, Emma Verheye, Elke De Bruyne, Eline Menu, Nathan De Beule, Ann De Becker, Gamze Ates, Ann Massie, Tessa Kerre, Marie Torngren, Helena Eriksson, Karin Vanderkerken, Karine Breckpot, Ken Maes, Kim De Veirman
Summary: This study identifies S100A9 as a novel molecular target for treating AML. Targeting S100A9 can reduce the viability and proliferation of AML cells by inhibiting mTOR and endoplasmic reticulum stress signaling, and increase the sensitivity of AML cells to venetoclax. The clinically available S100A9 inhibitor tasquinimod also has similar therapeutic effects. These findings are of great importance for the treatment of AML.
BLOOD CANCER JOURNAL
(2023)