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Articles 31 - 59 of 59
Full-Text Articles in Medicine and Health Sciences
Treatment Of Infantile Spasms: Emerging Insights From Clinical And Basic Science Perspectives, Carl Stafstrom, Barry Arnason, Tallie Baram, Anna Catania, Miguel Cortez, Tracy Glauser, Michael Pranzatelli, Raili Riikonen, Michael Rogawski, Shlomo Shinnar, John Swann
Treatment Of Infantile Spasms: Emerging Insights From Clinical And Basic Science Perspectives, Carl Stafstrom, Barry Arnason, Tallie Baram, Anna Catania, Miguel Cortez, Tracy Glauser, Michael Pranzatelli, Raili Riikonen, Michael Rogawski, Shlomo Shinnar, John Swann
Michael A. Rogawski
Infantile spasms is an epileptic encephalopathy of early infancy with specific clinical and electroencephalographic (EEG) features, limited treatment options, and a poor prognosis. Efforts to develop improved treatment options have been hindered by the lack of experimental models in which to test prospective therapies. The neuropeptide adrenocorticotropic hormone (ACTH) is effective in many cases of infantile spasms, although its mechanism(s) of action is unknown. This review describes the emerging candidate mechanisms that can underlie the therapeutic effects of ACTH in infantile spasms. These mechanisms can ultimately help to improve understanding and treatment of the disease. An overview of current treatments …
Seizure Protection By Intrapulmonary Delivery Of Propofol Hemisuccinate, Ashish Dhir, Dorota Zolkowska, Randall B. Murphy, Michael A. Rogawski
Seizure Protection By Intrapulmonary Delivery Of Propofol Hemisuccinate, Ashish Dhir, Dorota Zolkowska, Randall B. Murphy, Michael A. Rogawski
Michael A. Rogawski
The lung provides a portal of entry for drug delivery that could be used to administer anticonvulsant substances to prevent or abort seizures. Here we demonstrate that intrapulmonary propofol hemisucinate (PHS) rapidly confers seizure protection in various rodent chemoconvulsant models. Propofol is a powerful anticonvulsant substance at subanesthetic doses but it is a viscous, water-immiscible oil that is not suitable for intrapulmonary administration. We found that PHS can be formulated as an aqueous solution that is well tolerated when instilled into the lung. High dose intraperitoneal PHS induced loss-of-righting reflex in rats and mice. The onset of action of PHS …
Ganaxolone Suppression Of Behavioral And Electrographic Seizures In The Mouse Amygdala Kindling Model, Doodipala S. Reddy, Michael A. Rogawski
Ganaxolone Suppression Of Behavioral And Electrographic Seizures In The Mouse Amygdala Kindling Model, Doodipala S. Reddy, Michael A. Rogawski
Michael A. Rogawski
Ganaxolone (3alpha-hydroxy-3alpha-methyl-5alpha-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABA-A receptors, may represent a new treatment approach for epilepsy. Here we demonstrate that pretreatment with ganaxolone (1.25—20 mg/kg, s.c.) causes a dose-dependent suppression of behavioral and electrographic seizures in fully amygdala-kindled female mice, with nearly complete seizure protection at the highest dose tested. The ED50 for suppression of behavioral seizures was 6.6 mg/kg. The seizure suppression produced by ganaxolone was comparable to that of clonazepam (ED50, 0.1 mg/kg, s.c.). To the extent that amygdala kindling represents a model of mesial temporal lobe epilepsy, …
Neurosteroids On The Epilepsy Chessboard — Keeping Seizures In Check, Michael A. Rogawski
Neurosteroids On The Epilepsy Chessboard — Keeping Seizures In Check, Michael A. Rogawski
Michael A. Rogawski
No abstract provided.
Treatment Of Early And Late Kainic-Acid Induced Status Epilepticus With The Non-Competitive Ampa Receptor Antagonist Gyki 52466, Brita Fritsch, Jeffrey J. Stott, J. Joelle Donofrio, Michael A. Rogawski
Treatment Of Early And Late Kainic-Acid Induced Status Epilepticus With The Non-Competitive Ampa Receptor Antagonist Gyki 52466, Brita Fritsch, Jeffrey J. Stott, J. Joelle Donofrio, Michael A. Rogawski
Michael A. Rogawski
Purpose: Benzodiazepines such as diazepam may fail to effectively treat status epilepticus because benzodiazepine-sensitive GABA-A receptors are internalized progressively with continued seizure activity. Ionotropic glutamate receptors, including AMPA receptors, are externalized, so that AMPA receptor antagonists, which are broad-spectrum anticonvulsants, could be more effective treatments for satus epilepticus. We assessed the ability of the non-competitive AMPA receptor antagonist GYKI 52466 to protect against kainic acid-induced status epilepticus in mice. Methods: Groups of animals treated with kainic acid received GYKI 52466 (50 mg/kg followed in 15 min by 50 mg/kg) or diazepam (25 mg/kg followed in 20 min by 12.5 mg/kg) …
Anticonvulsant And Proconvulsant Actions Of 2-Deoxy-D-Glucose, Maciej Gasior, Jessica Yankura, Adam L. Hartman, Amy French, Michael A. Rogawski
Anticonvulsant And Proconvulsant Actions Of 2-Deoxy-D-Glucose, Maciej Gasior, Jessica Yankura, Adam L. Hartman, Amy French, Michael A. Rogawski
Michael A. Rogawski
Purpose: 2-Deoxy-D-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. …
Nontraditional Epilepsy Treatment Approaches, Michael A. Rogawski, Gregory L. Holmes
Nontraditional Epilepsy Treatment Approaches, Michael A. Rogawski, Gregory L. Holmes
Michael A. Rogawski
Overview of articles published in a special issue of Neurotherapeutics (April 2009) on nontraditional (non-drug) epilepsy treatment approaches. From the Fourth Workshop on New Horizons in the Development of Antiepileptic Drugs: Nontraditional Approaches to Treat Epilepsy, which was held at the Clontarf Castle, Dublin, March 5-7, 2008.
Convection-Enhanced Delivery In The Treatment Of Epilepsy, Michael A. Rogawski
Convection-Enhanced Delivery In The Treatment Of Epilepsy, Michael A. Rogawski
Michael A. Rogawski
Convection-enhanced delivery (CED) is a novel drug-delivery technique that uses positive hydrostatic pressure to deliver a fluid containing a therapeutic substance by bulk flow directly into the interstitial space within a localized region of the brain parenchyma. CED circumvents the blood-brain barrier and provides a wider, more homogenous distribution than bolus deposition (focal injection) or other diffusion-based delivery approaches. A potential use of CED is for the local delivery of antiseizure agents, which would provide an epilepsy treatment approach that avoids the systemic toxicities of orally administered anti-epileptic drugs and bystander effects on nonepileptic brain regions. Recent studies have demonstrated …
Topiramate Reduces Excitability In The Basolateral Amygdala By Selectively Inhibiting Gluk1 (Glur5) Kainate Receptors On Interneurons And Positively Modulating Gaba-A Receptors On Principal Neurons, Maria Braga, Vassiliki Aroniadou-Anderjaska, He Li, Michael Rogawski
Topiramate Reduces Excitability In The Basolateral Amygdala By Selectively Inhibiting Gluk1 (Glur5) Kainate Receptors On Interneurons And Positively Modulating Gaba-A Receptors On Principal Neurons, Maria Braga, Vassiliki Aroniadou-Anderjaska, He Li, Michael Rogawski
Michael A. Rogawski
Topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] is a structurally novel antiepileptic drug that has broad efficacy in epilepsy, but the mechanisms underlying its therapeutic activity are not fully understood. We have found that topiramate selectively inhibits GluK1 (GluR5) kainate receptor-mediated excitatory postsynaptic responses in rat basolateral amygdala (BLA) principal neurons and protects against seizures induced by the GluK1 kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA). Here, we demonstrate that topiramate also modulates inhibitory function in the BLA. Using whole-cell recordings in rat amygdala slices, we found that 0.3 to 10 microM topiramate 1) inhibited ATPA-evoked postsynaptic currents recorded from BLA interneurons; 2) suppressed ATPA-induced …
Pathological Alterations In Gabaergic Interneurons And Reduced Tonic Inhibition In The Basolateral Amygdala During Epileptogenesis, Michael A. Rogawski, Brita Fritsch, Felicia Qashu, T. H. Figueiredo, Vicki Aroniadou-Anderjaska, Maria F.M. Braga
Pathological Alterations In Gabaergic Interneurons And Reduced Tonic Inhibition In The Basolateral Amygdala During Epileptogenesis, Michael A. Rogawski, Brita Fritsch, Felicia Qashu, T. H. Figueiredo, Vicki Aroniadou-Anderjaska, Maria F.M. Braga
Michael A. Rogawski
An acute brain insult such as traumatic head/brain injury, stroke, or an episode of status epilepticus can trigger epileptogenesis, which, after a latent, seizure-free period, leads to epilepsy. The discovery of effective pharmacological interventions that can prevent the development of epilepsy requires knowledge of the alterations that occur during epileptogenesis in brain regions that play a central role in the induction and expression of epilepsy. In the present study, we investigated pathological alterations in GABAergic interneurons in the rat basolateral amygdala (BLA), and the functional impact of these alterations on inhibitory synaptic transmission, on days 7 to 10 after status …
Antiepileptic Drugs And Migraine, Michael Rogawski
Antiepileptic Drugs And Migraine, Michael Rogawski
Michael A. Rogawski
Prepared for the 16th International Headache Research Seminar, “Innovative Drug Development For Headache Disorders,” March 23–25, 2007, Copenhagen, Denmark.
Cellular Effects Of Antiepileptic Drugs, Robert L. Macdonald, Michael A. Rogawski
Cellular Effects Of Antiepileptic Drugs, Robert L. Macdonald, Michael A. Rogawski
Michael A. Rogawski
Antiepileptic drugs (AEDs) protect against seizures through interactions with a variety of cellular targets, which include various ion channels, a neurotransmitter transporter, a neurotransmitter metabolic enzyme, and a synaptic vesicle protein. AED actions on these targets can be categorized into four broad groups: 1. Modulation of voltage-dependent ion channels (mainly sodium [Na] but also calcium [Ca] channels) 2. Effects on γ-aminobutyric acid (GABA) systems, including alterations in the cellular disposition of GABA and enhancement of synaptic inhibition mediated by GABA-A receptors 3. Inhibition of synaptic excitation mediated by ionotropic glutamate receptors 4. Modulation of neurotransmitter release, particularly of glutamate, through …
Common Pathophysiologic Mechanisms In Migraine And Epilepsy, Michael A. Rogawski
Common Pathophysiologic Mechanisms In Migraine And Epilepsy, Michael A. Rogawski
Michael A. Rogawski
Migraine and epilepsy are comorbid episodic disorders that have common pathophysiologic mechanisms. Migraine attacks, like epileptic seizures, may be triggered by excessive neocortical cellular excitability; in migraine, however, the hyperexcitability is believed to transition to cortical spreading depression rather than to the hypersynchronous activity that characterizes seizures. Some forms of epilepsy and migraine are known to be channelopathies. Mutations in the same genes can cause either migraine or epilepsy or, in some cases, both. Given the likely commonalities in the underlying cellular and molecular mechanisms, it is not surprising that some antiepileptic drugs, including valproate, topiramate, and gabapentin, are effective …
The Neuropharmacology Of The Ketogenic Diet, Adam Hartman, Maciej Gasior, Elaine Vining, Michael Rogawski
The Neuropharmacology Of The Ketogenic Diet, Adam Hartman, Maciej Gasior, Elaine Vining, Michael Rogawski
Michael A. Rogawski
The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone …
Epilepsy: Mechanisms Of Drug Action And Clinical Treatment, William Theodore, Michael Rogawski
Epilepsy: Mechanisms Of Drug Action And Clinical Treatment, William Theodore, Michael Rogawski
Michael A. Rogawski
No abstract provided.
The Anticonvulsant Activity Of Acetone, The Major Ketone Body In The Ketogenic Diet, Is Not Dependent On Its Metabolites Acetol, 1,2-Propanediol, Methylglyoxal, Or Pyruvic Acid, Maciej Gasior, Amy French, Michelle Joy, Rebecca Tang, Adam Hartman, Michael Rogawski
The Anticonvulsant Activity Of Acetone, The Major Ketone Body In The Ketogenic Diet, Is Not Dependent On Its Metabolites Acetol, 1,2-Propanediol, Methylglyoxal, Or Pyruvic Acid, Maciej Gasior, Amy French, Michelle Joy, Rebecca Tang, Adam Hartman, Michael Rogawski
Michael A. Rogawski
BACKGROUND: Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown, but it is metabolized to several bioactive substances that could play a role. METHODS: Acetone and its major metabolites-acetol, 1,2-propanediol, methylglyoxal, and pyruvic acid-were assessed for anticonvulsant activity in two mouse seizure models. Various doses of the substances administered intraperitoneally were characterized for their ability to elevate the threshold for clonic seizures induced by intravenous infusion of pentylenetetrazol (PTZ) and for protection against tonic …
Molecular Targets For Antiepileptic Drug Development, Brian S. Meldrum, Michael A. Rogawski
Molecular Targets For Antiepileptic Drug Development, Brian S. Meldrum, Michael A. Rogawski
Michael A. Rogawski
This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the alpha subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, alpha2-delta voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ …
Neuroprotective And Disease-Modifying Effects Of The Ketogenic Diet, Maciej Gasior, Michael A. Rogawski, Adam L. Hartman
Neuroprotective And Disease-Modifying Effects Of The Ketogenic Diet, Maciej Gasior, Michael A. Rogawski, Adam L. Hartman
Michael A. Rogawski
The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated …
Alcohol Withdrawal Seizures, Michael A. Rogawski, Prosper N'Gouemo
Alcohol Withdrawal Seizures, Michael A. Rogawski, Prosper N'Gouemo
Michael A. Rogawski
No abstract provided.
The Neurobiology Of Antiepileptic Drugs, Michael Rogawski, Wolfgang Löscher
The Neurobiology Of Antiepileptic Drugs, Michael Rogawski, Wolfgang Löscher
Michael A. Rogawski
Antiepileptic drugs (AEDs) provide satisfactory control of seizures for most patients with epilepsy. The drugs have the remarkable ability to protect against seizures while permitting normal functioning of the nervous system. AEDs act on diverse molecular targets to selectively modify the excitability of neurons so that seizure-related firing is blocked without disturbing non-epileptic activity. This occurs largely through effects on voltage-gated sodium and calcium channels, or by promoting inhibition mediated by GABA-A (γ-aminobutyric acid, type A) receptors. The subtle biophysical modifications inchannel behaviour that are induced by AEDs are often functionally opposite to defects in channel properties that are caused …
Neurosteroids: Endogenous Modulators Of Seizure Susceptibility, Michael A. Rogawski, Doodipala S. Reddy
Neurosteroids: Endogenous Modulators Of Seizure Susceptibility, Michael A. Rogawski, Doodipala S. Reddy
Michael A. Rogawski
No abstract provided.
Principles Of Antiepileptic Drug Action, Michael Rogawski
Principles Of Antiepileptic Drug Action, Michael Rogawski
Michael A. Rogawski
No abstract provided.
Epilepsy (Ionotropic Glutamate Receptors As Therapeutic Targets), Wolfgang Löscher, Michael A. Rogawski
Epilepsy (Ionotropic Glutamate Receptors As Therapeutic Targets), Wolfgang Löscher, Michael A. Rogawski
Michael A. Rogawski
No abstract provided.
Role Of Ampa And Glur5 Kainate Receptors In The Development And Expression Of Amygdala Kindling In The Mouse, Michael A. Rogawski, Philip S. Kurzman, Shun-Ichi Yamaguchi, He Li
Role Of Ampa And Glur5 Kainate Receptors In The Development And Expression Of Amygdala Kindling In The Mouse, Michael A. Rogawski, Philip S. Kurzman, Shun-Ichi Yamaguchi, He Li
Michael A. Rogawski
The role of AMPA and GluR5-containing kainate receptors in the development and expression of amygdala kindling was examined using the selective 2,3-benzodiazepine AMPA receptor antagonist GYKI 52466 [(1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2, 3-benzodiazepine] and the decahydroisoquinoline mixed AMPA receptor and GluR5 kainate receptor antagonist LY293558 {(3S,4aR,6R, 8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline- 3-carboxy lic acid)}. Administration of GYKI 52466 (5-40 mg/kg, intraperitoneally) and LY293558 (10-40 mg/kg, intraperitoneally) prior to daily kindling stimulation in mice produced a dose-dependent suppression of the rate of development of behavioral kindled seizure activity and reduced the duration of the stimulation-induced electrographic afterdischarge. In drug-free stimulation sessions after the initial drug-treatment sessions, there was an …
Of Blind Men And Brain Steroids, Michael A. Rogawski
Of Blind Men And Brain Steroids, Michael A. Rogawski
Michael A. Rogawski
Review of "Neurosteroids: A New Regulatory Function in the Nervous System" (edited by Etiene-Emile Baulieu, Paul Robel and Michael Schumacher), Humana Press, 1999. ISBN 0896 03545X The first recognized example of the profound influence of steroid hormones on the nervous system was perhaps the observation in prehistoric times that animal behaviour changes dramatically during oestrus (the period of female sexual receptivity). In recent years, much specific evidence has accumulated confirming that steroids affect the structure and function of the nervous system through effects on neurogenesis, cell death, cell migration, synapse formation and neuronal excitability.
Ampa Receptors In Epilepsy And As Targets For Antiepileptic Drugs, Michael A. Rogawski, Sean D. Donevan
Ampa Receptors In Epilepsy And As Targets For Antiepileptic Drugs, Michael A. Rogawski, Sean D. Donevan
Michael A. Rogawski
No abstract provided.
Epilepsy, Michael Rogawski
Excitatory Amino Acids And Seizures, Michael A. Rogawski
Excitatory Amino Acids And Seizures, Michael A. Rogawski
Michael A. Rogawski
No abstract provided.
Antiepileptic Drugs: Pharmacological Mechanisms And Clinical Efficacy With Consideration Of Promising Developmental Stage Compounds, Michael A. Rogawski, Roger J. Porter
Antiepileptic Drugs: Pharmacological Mechanisms And Clinical Efficacy With Consideration Of Promising Developmental Stage Compounds, Michael A. Rogawski, Roger J. Porter
Michael A. Rogawski
No abstract provided.