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Articles 1 - 7 of 7
Full-Text Articles in Neurosciences
Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff
Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff
Michael A. Rogawski
The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropanamide], a chiral functionalized amino acid, was originally identified by virtue of activity in the mouse and rat maximal electroshock (MES) test. Attention was drawn to lacosamide because of its high oral potency and stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but inactive against clonic seizures in rodents induced by subcutaneous pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic models of absence epilepsy. At doses greater than those required to confer protection in the MES test, lacosamide inhibits behavioral and electrographic seizures in hippocampal kindled rats. It also effectively terminates …
Pediatric Super-Refractory Status Epilepticus Treated With Allopregnanolone, Eileen Broomall, Joanne Natale, Michele Grimason, Joshua Goldstein, Craig Smith, Celia Chang, Stephen Kanes, Michael Rogawski, Mark Wainwright
Pediatric Super-Refractory Status Epilepticus Treated With Allopregnanolone, Eileen Broomall, Joanne Natale, Michele Grimason, Joshua Goldstein, Craig Smith, Celia Chang, Stephen Kanes, Michael Rogawski, Mark Wainwright
Michael A. Rogawski
Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic GABA-A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABA-A receptors. Here we describe the use of allopregnanolone in two pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children.
The Potential Of Antiseizure Drugs And Agents That Act On Novel Molecular Targets As Antiepileptogenic Treatments, Rafal M. Kaminski, Michael A. Rogawski, Henrik Klitgaard
The Potential Of Antiseizure Drugs And Agents That Act On Novel Molecular Targets As Antiepileptogenic Treatments, Rafal M. Kaminski, Michael A. Rogawski, Henrik Klitgaard
Michael A. Rogawski
A major goal of contemporary epilepsy research is the identification of therapies to prevent the development of recurrent seizures in individuals at risk, including those with brain injuries, infections, or neoplasms; status epilepticus; cortical dysplasias; or genetic epilepsy susceptibility. In this review we consider the evidence largely from preclinical models for the antiepileptogenic activity of a diverse range of potential therapies, including some marketed antiseizure drugs, as well as agents that act by immune and inflammatory mechanisms; reduction of oxidative stress; activation of the mammalian target of rapamycin or peroxisome proliferator-activated receptors γ pathways; effects on factors related to thrombolysis, …
Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski
Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski
Michael A. Rogawski
Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target synaptosomal-associated protein 25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 Unit) …
Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski
Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski
Michael A. Rogawski
Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. Here we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully-kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-min period by convection enhanced delivery (CED). Electrographic (EEG) and behavioral …
Epilepsy Therapy Development: Technical And Methodologic Issues In Studies With Animal Models, Aristea S. Galanopoulou, Merab Kokaia, Jeffrey A. Loeb, Astrid Nehlig, Asla Pitkanen, Michael A. Rogawski, Kevin J. Staley, Vicky H. Whittemore, F. Edward Dudek
Epilepsy Therapy Development: Technical And Methodologic Issues In Studies With Animal Models, Aristea S. Galanopoulou, Merab Kokaia, Jeffrey A. Loeb, Astrid Nehlig, Asla Pitkanen, Michael A. Rogawski, Kevin J. Staley, Vicky H. Whittemore, F. Edward Dudek
Michael A. Rogawski
The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting …
Epilepsy, Michael Rogawski