A5005402221- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Alzheimer's disease research and treatments
- Pharmacological Effects and Toxicity Studies
- Ion channel regulation and function
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Memory and Neural Mechanisms
- Molecular Sensors and Ion Detection
- Gut microbiota and health
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Drug Transport and Resistance Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Cannabis and Cannabinoid Research
- Pharmacogenetics and Drug Metabolism
- Sulfur Compounds in Biology
- Amino Acid Enzymes and Metabolism
- Clostridium difficile and Clostridium perfringens research
- Genetics and Neurodevelopmental Disorders
- Ethics in Clinical Research
- Biomedical Research and Pathophysiology
- Cholesterol and Lipid Metabolism
- Cytomegalovirus and herpesvirus research
University of Washington
2016-2025
Seattle University
2021
Melior Discovery (United States)
2018
Marinus Pharmaceuticals (United States)
2018
University of Utah
2009-2016
Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in battery acute seizure models. Additionally, we defined disease-modifying potential chronic oral administration CBD on associated comorbidities reduced intensity status epilepticus-spontaneous (RISE-SRS) model temporal lobe epilepsy (TLE).
Summary Animal models have provided a wealth of information on mechanisms epileptogenesis and comorbidogenesis, significantly advanced our ability to investigate the potential new therapies. Processes implicating brain inflammation been increasingly observed in epilepsy research. Herein we discuss progress animal comorbidities that inform us role comorbidity pathogenesis rodent West syndrome Theiler's murine encephalomyelitis virus ( TMEV ) mouse model viral encephalitis–induced epilepsy....
It is estimated that 30%-40% of epilepsy patients are refractory to therapy and animal models useful for the identification more efficacious therapeutic agents. Various well-characterized syndrome-specific needed assess their relevance human seizure disorders validity testing potential therapies. The corneal kindled mouse model temporal lobe (TLE) allows rapid screening investigational compounds, but there a lack information as specific inflammatory pathology in this model. Similarly,...
Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice induces acute seizures and development of spontaneous recurrent behavioral comorbidities weeks later. The present studies sought to determine whether therapeutic intervention an anti-inflammatory-based approach could prevent or modify TMEV-induced long-term comorbidities. Valproic acid (VPA), addition its prototypical anticonvulsant properties, inhibits histone deacetylase (HDAC) activity, which may alter...
Ganaxolone (GNX) is the 3<i>β</i>-methylated synthetic analog of naturally occurring neurosteroid, allopregnanolone (ALLO). GNX effective in a broad range epilepsy and behavioral animal models currently clinical trials designed to assess its anticonvulsant antidepressant activities. The current studies were broaden profile by evaluating potential activities following i.v. administration treatment-resistant status epilepticus (SE), establish pharmacokinetic (PK)/pharmacodynamic (PD)...
Seizures in people with Alzheimer's disease are increasingly recognized to worsen burden and accelerate functional decline. Harnessing established antiseizure medicine discovery strategies rodents associated risk genes represents a novel way uncover modifying treatments that may benefit these patients. This commentary discusses the recent evaluation by Dejakaisaya colleagues assess disease-modifying potential of repurposed cephalosporin antibiotic, ceftriaxone, Tg2576 mouse model. The use...
Antiseizure medicines (ASMs) cause both acute and chronic behavioral side effects in individuals with epilepsy. While clinical preclinical studies often focus on effects, the dose-related impact of ASMs behavior is underreported, especially rodent models temporal lobe epilepsy (TLE). Investigating therapeutic behaviorally impairing doses may help predict clinically-relevant adverse such as sedation, hyperactivity, impaired coordination, which are essential for evaluating drug safety...
Abstract Objective γ‐Aminobutyric acid type A (GABA ) receptor positive allosteric modulators (PAMs) that lack α‐subunit selectivity, including benzodiazepines such as diazepam, exhibit antiseizure actions in animal models and humans. ENX‐101 is a deuterated analog of the ⍺2,3,5‐selective GABA PAM L‐838,417. The purpose this study was to characterize selectivity evaluate its potential preclinical seizure epilepsy models. Methods potentiation chloride current responses cells expressing...
Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from CAG repeat expansion in the atrophin-1 (ATN1) gene. Because DRPLA, like many disorders (REDs), arises predominantly toxic gain-of-function mechanisms, we hypothesized that ATN1 knockdown would have therapeutic potential. To test this, established first fully-humanized mouse model of RED, which one allele Atn1 completely replaced by human ATN1, including 112 pure repeats. This novel approach to...
Abstract Objective Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice produces an etiologically relevant model of acquired seizures. Dietary changes can modify seizure presentation following TMEV brain and influence intestinal microbiome diversity composition. Intestinal dysbiosis may thus similarly affect burden antiseizure medicine (ASM) activity this model, independent pharmacokinetic effects. We sought to define the antibiotic (ABX)‐induced gut on acute...
Objective: Central to the development of novel antiseizure medications (ASMs) is testing anticonvulsant activity in preclinical models. While various well-established models exist, their predictive validity across spectrum clinical epilepsies has been less clear. We sought establish translational concordance commonly used define with highest for focal onset seizures (FOS). Methods: The Praxis Analysis Concordance (PAC) framework was implemented assess between and ASM response 32 FDA-approved...
Central nervous system infections can underlie the development of epilepsy, and Theiler’s murine encephalomyelitis virus (TMEV) infection in C57BL/6J mice provides a novel model infection-induced epilepsy. Approximately 50–65% infected develop acute, handling-induced seizures during infection. Brains display acute neuropathology, high number spontaneous, recurrent behavioral comorbidities weeks later. This study characterized utility this for drug testing by assessing whether antiseizure...
Summary Objective Some antiseizure drugs ( ASD s) are associated with cognitive liability in patients epilepsy, thus s without this risk would be preferred. Little comparative pharmacology exists preclinical models of cognition. Few pharmacologic studies exist on the acute effects rodents chronic seizures. Predicting for impact may supply valuable differentiation data. Methods (phenytoin [ PHT ]; carbamazepine CBZ valproic acid VPA lamotrigine LTG phenobarbital PB tiagabine TGB retigabine...
Summary Objective Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs ( ASD s). Thus, there is a strong need more effective s these individuals. Early discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy. Etiologically relevant rodent pharmacoresistant epilepsy exist (eg, phenytoin PHT )‐ and...
Abstract Objective Epileptic spikes and seizures seem present early in the disease process of Alzheimer's (AD). However, it is unclear how soluble insoluble amyloid beta (Aβ) tau proteins affect seizure development vivo. We aim to contribute this field by assessing vulnerability 6 Hz corneal kindling young female mice from two well‐characterized transgenic AD models testing their responsiveness selected antiseizure drugs (ASDs). Methods used 7‐week‐old triple (3xTg) that have both mutations,...