Article
Biochemistry & Molecular Biology
Ilia G. Komoltsev, Stepan O. Frankevich, Natalia I. Shirobokova, Aleksandra A. Volkova, Mikhail V. Onufriev, Julia V. Moiseeva, Margarita R. Novikova, Natalia V. Gulyaeva
Summary: This study using a rat TBI model found that immediate post-traumatic seizures and changes in corticosterone levels may be associated with neuroinflammation-mediated distant hippocampal damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Line Skotte, Joao Fadista, Jonas Bybjerg-Grauholm, Vivek Appadurai, Michael S. Hildebrand, Thomas F. Hansen, Karina Banasik, Jakob Grove, Clara Albinana, Frank Geller, Carmen F. Bjurstrom, Bjarni J. Vilhjalmsson, Matthew Coleman, John A. Damiano, Rosemary Burgess, Ingrid E. Scheffer, Ole Birger Vesterager Pedersen, Christian Erikstrup, David Westergaard, Kaspar Rene Nielsen, Erik Sorensen, Mie Topholm Bruun, Xueping Liu, Henrik Hjalgrim, Tune H. Pers, Preben Bo Mortensen, Ole Mors, Merete Nordentoft, Julie W. Dreier, Anders D. Borglum, Jakob Christensen, David M. Hougaard, Alfonso Buil, Anders Hviid, Mads Melbye, Henrik Ullum, Samuel F. Berkovic, Thomas Werge, Bjarke Feenstra
Summary: This study conducted a genome-wide association study of febrile seizures and discovered seven new loci, as well as confirmed four previously reported loci, all related to genes associated with central fever response, neuronal excitability, and epilepsy. The findings also showed positive genetic correlations with epilepsy and a lower polygenic risk in febrile seizure patients with neuropsychiatric disease.
Review
Biochemistry & Molecular Biology
Enrico Pracucci, Vinoshene Pillai, Didi Lamers, Riccardo Parra, Silvia Landi
Summary: Epilepsy can be both a primary pathology and a secondary effect of many neurological conditions. Neuroinflammation is believed to be a product of epilepsy, and conditions characterized by neuroinflammation are more likely to develop epilepsy. However, the bidirectional mechanism of the reciprocal interaction between epilepsy and neuroinflammation still needs further understanding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Krzysztof Lukawski, Stanislaw J. Czuczwar
Summary: Free radicals are generated in the brain and other organs, and their production is related to brain activity. The brain is particularly vulnerable to free radical damage due to its low antioxidant capacity, which can affect lipids, nucleic acids, and proteins. Oxidative stress plays a role in neuronal death and the development of epilepsy, and this review examines free radical generation in animal models of seizures and epilepsy, as well as the consequences of oxidative stress and the potential use of antioxidant drugs in patients with epilepsy.
Article
Multidisciplinary Sciences
Murat Kirtay, Josefine Sell, Christian Marx, Holger Haselmann, Mihai Ceanga, Zhong-Wei Zhou, Vahid Rahmati, Joanna Kirkpatrick, Katrin Buder, Paulius Grigaravicius, Alessandro Ori, Christian Geis, Zhao-Qi Wang
Summary: ATR, a key regulator of DNA damage response and replication stress, also plays a role in regulating neuronal activity beyond its known functions. Deletion of ATR in neurons leads to increased intrinsic activity, aberrant firing, and heightened epileptiform activity, potentially increasing susceptibility to ataxia and epilepsy.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Adriana L. Hotz, Ahmed Jamali, Nicolas N. Rieser, Stephanie Niklaus, Ecem Aydin, Sverre Myren-Svelstad, Laetitia Lalla, Nathalie Jurisch-Yaksi, Emre Yaksi, Stephan C. F. Neuhauss
Summary: The loss of function in the astroglia predominant eaat2a gene in zebrafish leads to altered neuronal and astroglial networks, resulting in epileptic seizures and increased extracellular glutamate levels. Interestingly, while hyperexcitability is observed during seizures, basal neuronal and astroglial activity is reduced, leading to decreased overall locomotion in eaat2a(-/-) mutant animals.
Article
Multidisciplinary Sciences
Silvia Y. Bando, Fernanda B. Bertonha, Pedro H. N. Menezes, Andre K. Takahara, Nathalia A. Khaled, Paula Santos, Mara S. Junqueira, Roberto M. Cesar, Carlos A. Moreira-Filho
Summary: Febrile seizures in early childhood pose a risk for developing epilepsy of the mesial temporal lobe, however, the underlying molecular mechanisms remain poorly understood. Therefore, rat models of hyperthermia-induced seizures have been used to investigate these mechanisms.
SCIENTIFIC REPORTS
(2023)
Review
Behavioral Sciences
Esther Pototskiy, Joshua Ryan Dellinger, Stuart Bumgarner, Jay Patel, William Sherrerd-Smith, Alberto E. Musto
Summary: Effective prophylactic therapies to prevent the onset of epilepsy are currently lacking due to a lack of understanding in fundamental neurobiological mechanisms and reliable biomarkers. Dysfunctions in neural networks may lead to epileptogenesis and seizure occurrence and progression.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Karol Wisniewski, Tomasz Antonowski, Judyta Juranek, Piotr Podlasz, Joanna Wojtkiewicz
Summary: Epilepsy, affecting about 70 million people worldwide, poses a significant challenge to medicine. In this study, the potential antiepileptic properties of scyllo-inositol (SCI) were tested in zebrafish larvae with seizures induced by pentylenetetrazol. Short-term exposure to SCI reduced larva motility, while long-term exposure did not produce similar results, possibly due to insufficient concentration of SCI. These findings highlight the potential of SCI in epilepsy treatment and call for further clinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Rohit Pal, Bhupinder Kumar, Md. Jawaid Akhtar, Pooja A. Chawla
Summary: Voltage-gated sodium channel blockers are important targets for managing central nervous system diseases such as epilepsy, chronic pain, psychiatric disorders, and spasticity. These drugs work by reducing excitotoxicity and improving symptoms, with several new drugs in development to target abnormal neuronal excitability. Despite extensive research, there has been no groundbreaking discovery yet in controlling seizures through sodium channel blockers, and ongoing efforts are focused on developing more potent anticonvulsant drugs with minimized toxicity.
BIOORGANIC CHEMISTRY
(2021)
Article
Neurosciences
Arena Manning, Victor Han, Alexa Stephens, Rose Wang, Nicholas Bush, Michelle Bard, Jan M. Ramirez, Franck Kalume
Summary: Mutations in the NDUFS4 gene can lead to Leigh syndrome (LS), the most common form of mitochondrial disease in children. Epileptic seizures, which are difficult to treat and indicate poor prognosis, are a significant clinical feature of LS. By studying the effects of Ndufs4 gene mutations in GABAergic interneurons of mice, we gain insights into the epilepsy phenotype of LS and the cellular mechanisms underlying epilepsy in LS and other mitochondrial diseases.
NEUROBIOLOGY OF DISEASE
(2023)
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.
Review
Clinical Neurology
Naoum P. P. Issa, Katherine C. C. Nunn, Shasha Wu, Hiba A. A. Haider, James X. X. Tao
Summary: Homeostatic plasticity allows neural circuits to maintain activity levels and learn new associations, but can also contribute to seizures in certain conditions. Understanding the active homeostatic mechanisms in different stages of development and circuits can help target therapies and disrupt the cycle of recurring seizure clusters.
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
Henry Darch, Cian P. McCafferty
Summary: The gut microbiome has been found to have an influence on the excitability and activity of neurons, which is particularly significant in the context of epilepsy. Further research is needed to understand the mechanisms of this influence.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Cell Biology
Meagan Siehr, Cory Massey, Jeffrey L. Noebels
DISEASE MODELS & MECHANISMS
(2020)
Article
Toxicology
Eduardo A. Gonzalez, Alexa C. Rindy, Michelle A. Guignet, Jonas J. Calsbeek, Donald A. Bruun, Ashish Dhir, Peter Andrew, Naomi Saito, Douglas J. Rowland, Danielle J. Harvey, Michael A. Rogawski, Pamela J. Lein
ARCHIVES OF TOXICOLOGY
(2020)
Review
Neurosciences
Graeme J. Sills, Michael A. Rogawski
Article
Clinical Neurology
Alice D. Lam, Jeffrey Noebels
Article
Clinical Neurology
Dorota Zolkowska, Chun-Yi Wu, Michael A. Rogawski
Summary: Allopregnanolone administered intranasally rapidly elevates seizure threshold with minimal adverse effects, showing direct nose-to-brain delivery and preferential distribution in brain regions relevant to seizures compared to benzodiazepines. Intranasal delivery of allopregnanolone provides a rapid and effective treatment option for seizures, overcoming potential refractoriness to benzodiazepines.
Article
Toxicology
Dorota Zolkowska, Ashish Dhir, Michael A. Rogawski
Summary: The study found that perampanel and diazepam can effectively protect against TETS-induced tonic seizures and lethality, but have less impact on clonic seizures.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Clinical Neurology
Bjorn Oskarsson, Elizabeth A. Mauricio, Jaimin S. Shah, Zhuo Li, Michael A. Rogawski
Summary: This study aimed to evaluate transcranial magnetic stimulation (TMS) as a functional assessment tool for studying the effects of perampanel in ALS patients. Results demonstrated that perampanel affects the physiology of upper motor neurons, and motor threshold may serve as a marker of biological target engagement.
Article
Clinical Neurology
Gordon F. Buchanan, Bruce J. Gluckman, Franck K. Kalume, Samden Lhatoo, Rama K. Maganti, Jeffrey L. Noebels, Kristina A. Simeone, Mark S. Quigg, Milena K. Pavlova
Summary: SUDEP is the leading cause of death in patients with refractory epilepsy, with likely pathophysiological mechanisms including cardiac and respiratory dysregulation. SUDEP cases frequently occur at night, raising the question of a role for sleep in its regulation. Studies have identified an association with sleep in SUDEP and animal models, emphasizing the importance of understanding the role of sleep and time of day in its pathophysiology.
Article
Pharmacology & Pharmacy
Irene Vuu, Edward E. Patterson, Chun-Yi Wu, Dorota Zolkowska, Ilo E. Leppik, Michael A. Rogawski, Gregory A. Worrell, Vaclav Kremen, James C. Cloyd, Lisa D. Coles
Summary: This study characterizes the pharmacokinetics and pharmacodynamics of allopregnanolone, providing a basis for designing clinical studies evaluating its effectiveness as an early treatment for status epilepticus in dogs and people.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Neurosciences
Jonas J. Calsbeek, Eduardo A. Gonzalez, Casey A. Boosalis, Dorota Zolkowska, Donald A. Bruun, Douglas J. Rowland, Naomi H. Saito, Danielle J. Harvey, Abhijit J. Chaudhari, Michael A. Rogawski, Joel R. Garbow, Pamela J. Lein
Summary: Acute intoxication with tetramethylenedisulfotetramine (TETS) can trigger status epilepticus (SE) in humans. Survivors often exhibit long-term neurological effects, but the pathogenic mechanisms are not known. In this study, advanced in vivo imaging techniques were used to monitor the neuropathological consequences of TETS-induced SE in different mouse strains, revealing strain-specific differences in brain injury and neuroinflammation.
Article
Cell Biology
Justine H. Liang, Jonathan Alevy, Viktor Akhanov, Ryan Seo, Cory A. Massey, Danye Jiang, Joy Zhou, Roy V. Sillitoe, Jeffrey L. Noebels, Melanie A. Samuel
Summary: Mutations in the KCTD7 gene are associated with a severe neurodegenerative phenotype characterized by childhood onset of progressive and intractable myoclonic seizures accompanied by developmental regression. Kctd7-deficient mice develop similar symptoms, indicating that Kctd7 is involved in the pathogenesis of KCTD7-related diseases. Furthermore, Kctd7 is required for Purkinje cell survival in the cerebellum and is linked to microvascular alterations in vulnerable regions.
DISEASE MODELS & MECHANISMS
(2022)
Article
Clinical Neurology
Michael A. A. Rogawski, Gary Slatko
Summary: The pharmacokinetics of diazepam nasal spray can be affected by food, resulting in decreased and delayed absorption compared to fasting conditions. This study found that under fed conditions, the maximum plasma diazepam concentration and overall exposure were significantly reduced compared to fasted conditions. The time to reach maximum plasma concentration was also longer in the fed state. This has important implications for patients using diazepam nasal spray, as they may not achieve therapeutic concentrations if used after eating.
Article
Clinical Neurology
Donald A. Bruun, Betty Ma, Yi-Je Chen, Chun-Yi Wu, Monica Aleman, Dorota Zolkowska, Suzette M. Smiley-Jewell, Michael A. Rogawski, Pamela J. Lein
Summary: The study assessed the cardiopulmonary safety of intravenous ALLO for treating benzodiazepine-refractory SE. The results showed that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.
Meeting Abstract
Clinical Neurology
Christopher Kenney, Jacqueline French, Roger Porter, Emilio Perucca, Martin Brodie, Michael A. Rogawski, Cynthia Harden, Jenny Qian, Greg Beatch
Meeting Abstract
Clinical Neurology
Jacqueline French, Roger Porter, Emilio Perucca, Martin Brodie, Michael A. Rogawski, Simon Pimstone, Ernesto Aycardi, Cynthia Harden, Yi Xu, Constanza Luzon Rosenblut, Christopher Kenney, Greg Beatch