A5029883839- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Pharmacological Effects and Toxicity Studies
- Lipid Membrane Structure and Behavior
- Functional Brain Connectivity Studies
- Photoreceptor and optogenetics research
- Neurological disorders and treatments
- Sleep and Wakefulness Research
- Ion channel regulation and function
- Alzheimer's disease research and treatments
- Bipolar Disorder and Treatment
- Mitochondrial Function and Pathology
- Advanced Neuroimaging Techniques and Applications
- Cellular transport and secretion
- Drug Transport and Resistance Mechanisms
- Fetal and Pediatric Neurological Disorders
Yale University
2014-2022
University of New Haven
2021
University of Oslo
2021
Synaptic density in the living human brain was measured with positron emission tomography and a synaptic vesicle glycoprotein 2A tracer.
The objective of the present study is to identify novel, time-indexed imaging biomarkers epileptogenesis in mesial temporal lobe epilepsy (MTLE).We used high-resolution brain diffusion tensor (DTI) translationally relevant methionine sulfoximine (MSO) infusion model MTLE. MSO inhibits astroglial glutamine synthetase, which deficient epileptogenic hippocampal formation patients with MSO-infused (epileptogenic) rats were compared phosphate-buffered saline (PBS)-infused (nonepileptogenic) at...
To test the hypothesis that glutamate and GABA are linked to formation of epilepsy networks triggering spontaneous seizures, we examined seizure initiation/propagation characteristics neurotransmitter levels during epileptogenesis in a translationally relevant rodent model mesial temporal lobe epilepsy.The glutamine synthetase (GS) inhibitor methionine sulfoximine was infused into one hippocampi laboratory rats create focus. Long-term video-intracranial EEG recordings brain microdialysis...
The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis may either suppress or trigger acute seizures. However, effects of on chronic (ie, spontaneous recurrent) seizures epilepsy-associated neuron loss are incompletely understood.Sixteen rats with mesial temporal lobe epilepsy were...
Abstract Objective The astroglial enzyme glutamine synthetase (GS) is deficient in small loci the brain adult patients with different types of focal epilepsy; however, role this deficiency pathogenesis epilepsy has been difficult to assess due a lack sufficiently sensitive and specific animal models. aim study was develop an vivo approach for precise deletions GS gene postnatal brain. Methods We stereotaxically injected various adeno‐associated virus (AAV)–Cre recombinase constructs into...
Seizures often exhibit striking circadian-like (approximately 24-hour) rhythms. While chronotherapy has shown promise in treating epilepsy, it is not widely used, part because the patterns of seizure rhythmicity vary considerably among patients and types epilepsy. A better understanding mechanisms underlying epilepsy could be expected to result more effective approaches which can tailored each individual patient. The excitatory neurotransmitter glutamate an essential modulator circadian...
Abstract The objective of this study was to monitor the extracellular brain chemistry dynamics at baseline and in relation spontaneous seizures human patients with refractory epilepsy. Thirty drug‐resistant focal epilepsy underwent intracranial electroencephalography concurrent microdialysis for up 8 continuous days. Extracellular glutamate, glutamine, branched‐chain amino acids (BCAAs) valine, leucine, isoleucine were quantified dialysis samples by liquid chromatography–tandem mass...
Background: Glutamine synthetase (GS) is the only enzyme known to synthesize significant amounts of glutamine in mammals, and loss GS hippocampus has been implicated pathophysiology medication refractory mesial temporal lobe epilepsy (MTLE). Moreover, loss-of-function mutations gene causes severe epileptic encephalopathy, supplementation with shown normalize EEG possibly improve outcome these patients. Here we examined whether oral an effective treatment for MTLE by assessing frequency...
Temporal lobe epilepsy (TLE) and depression are common comorbid disorders whose underlying shared neural network has yet to be determined. Although animal studies demonstrate a role for the dorsal bed nucleus of stria terminalis (dBNST) in both seizures depression, human clinical therapeutic effect stimulating this region on treatment-resistant dBNST depressed nondepressed TLE patients is still unclear. Here, we tested hypothesis that structure morphologically abnormal these patients, with...
OBJECTIVES/SPECIFIC AIMS: We previously developed a translationally relevant model of temporal lobe epilepsy (TLE) in which glutamine synthetase is irreversibility inhibited by methionine sulfoximine (MSO), resulting spontaneous seizures and dentate hilar neuron loss. The objective this study was to determine the effects chronic BCAA ingestion on neuronal viability hilus MSO TLE. METHODS/STUDY POPULATION: Sixteen rats were randomly divided into 2 groups: 8 drank 4% aqueous solution all 3...
The objective of this study was to determine the effects oral supplementation with branched-chain amino acids (BCAAs) leucine, isoleucine, and valine on seizures neuronal viability in a rodent model mesial temporal lobe epilepsy (MTLE), common form medication-refractory focal epilepsy. Sixteen rats were randomly divided into two groups: eight drank 4% aqueous solution all three BCAAs (BCAA group) ad libitum for 31 days, other regular water (control same period. After 10 days drinking,...
OBJECTIVES/SPECIFIC AIMS: Astroglial glutamine synthetase (GS), which metabolizes glutamate and ammonia to glutamine, is critical for the detoxification of brain ammonia, clearance synaptic glutamate, production glutamine. Perturbations in expression activity GS are thought play a causative role pathogenesis several conditions abnormal neurotransmission. Although long-term consequences inhibition on amino acid homeostasis unknown, it that influx tightly coupled with efflux via L-type...