A5063811512- Neuroscience and Neuropharmacology Research
- Anesthesia and Sedative Agents
- Pain Mechanisms and Treatments
- Anesthesia and Neurotoxicity Research
- Treatment of Major Depression
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Public Health Policies and Education
- Renin-Angiotensin System Studies
- Tryptophan and brain disorders
- Sleep and Wakefulness Research
- Neuropeptides and Animal Physiology
- Neural dynamics and brain function
- Pharmacological Receptor Mechanisms and Effects
- Stress Responses and Cortisol
- Neurotransmitter Receptor Influence on Behavior
- Memory and Neural Mechanisms
- Pain Management and Placebo Effect
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Renal function and acid-base balance
- Global Public Health Policies and Epidemiology
- EEG and Brain-Computer Interfaces
- Sodium Intake and Health
- Intensive Care Unit Cognitive Disorders
- Photoreceptor and optogenetics research
University of Utah
2019-2024
Harvard University
2012-2019
Massachusetts General Hospital
2012-2018
Massachusetts Institute of Technology
1957-2017
American Society of Anesthesiologists
2014
Novem (Netherlands)
2014
Society for Neuroscience
2014
Shanghai Medical College of Fudan University
2010
New York Medical College
2010
Medical College of Wisconsin
2003-2010
Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine methylphenidate are effective for increasing arousal inducing reanimation, or active emergence from general anesthesia. neurons in the ventral tegmental area (VTA) involved reward processing, motivation, emotion, reinforcement, cognition, but their role regulating wakefulness is less clear. The current study was performed to test hypothesis that selective optogenetic activation of VTA sufficient...
Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests role for neuroinflammation, no study has directly provided of brain glial activation in FM. In this study, we conducted Positron Emission Tomography (PET) using [11C]PBR28, which binds to the translocator protein (TSPO), upregulated activated microglia astrocytes. To enhance statistical power generalizability,...
In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white (WM) and normal-appearing WM (NAWM) to investigate vivo pathological clinical relevance neuroinflammation.Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting (RRMS) 14 matched...
MicroRNAs are endogenous repressors of gene expression. We examined microRNAs in the renal medulla Dahl salt-sensitive rats and consomic SS-13(BN) rats. Salt-induced hypertension injury rats, particularly medullary interstitial fibrosis, have been shown previously to be substantially attenuated Of 377 examined, 5 were found differentially expressed between receiving a high-salt diet. Real-time PCR analysis demonstrated that diets induced substantial upregulation miR-29b but not SS was...
Dahl salt-sensitive (SS) rats exhibit increased renal medullary oxidative stress and blood pressure salt-sensitivity compared with consomic, salt-resistant SS-13BN rats, despite highly similar genetic backgrounds. The present study examined potential sources of superoxide in prehypertensive SS fed a 0.4% NaCl diet by assessing activity protein levels producing scavenging enzymes. Superoxide production was nearly doubled as determined urinary 8-isoprostane excretion oxy-ethidium...
Abstract Background: Methylphenidate or a D1 dopamine receptor agonist induces reanimation (active emergence) from general anesthesia. The authors tested whether electrical stimulation of dopaminergic nuclei also Methods: In adult rats, bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5) substantia nigra (n 5). After minimum 7-day recovery period, isoflurane dose sufficient to maintain loss righting established. Electrical initiated and increased...
Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine depressed current suicidal ideation remains unknown.Between April 2012 and October 2013, 14 outpatients DSM-IV-diagnosed major depressive disorder were recruited presence current, stable (≥ 3 months) thoughts. They received open-label infusions over weeks (0.5 mg/kg 45 minutes first infusions; 0.75 last 3). In this secondary...
Background: A recent study showed that methylphenidate induces emergence from isoflurane anesthesia.Methylphenidate inhibits dopamine and norepinephrine reuptake transporters.The objective of this was to test the hypothesis selective receptor activation anesthesia.Methods: In adult rats, we tested effects chloro-APB (D1 agonist) quinpirole (D2 on time general anesthesia.We then performed a dose-response for chloro-APBinduced restoration righting during continuous anesthesia.SCH-23390...
Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies lacking that have examined escalating doses augmentation in outpatients with treatment-resistant depression. Therefore, aims this study were twofold: (1) to assess antidepressant two-step, repeated-dose (2) duration ketamine’s ongoing pharmacotherapy for 3 months after final infusion. Methods:...
Abstract The periaqueductal gray (PAG) is a significant modulator of both analgesic and fear behaviors in humans rodents, but the underlying circuitry responsible for these two phenotypes incompletely understood. Importantly, it not known if there way to produce analgesia without anxiety by targeting PAG, as modulation glutamate or GABA neurons this area initiates antinociceptive anxiogenic behavior. While dopamine (DA) ventrolateral PAG (vlPAG)/dorsal raphe display supraspinal effect, their...
Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important producing this effect. Dextroamphetamine causes the direct release of dopamine norepinephrine, whereas atomoxetine a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In study, we tested efficacy dextroamphetamine inducing rats....
This report describes double-blind placebo-controlled trials of a new synthetic antirhinovirus drug, R61837, which showed it to be effective in suppressing colds human volunteers challenged with rhinovirus type 9. In one trial, R61837 was given by intranasal spray six times day, commencing 28 h before virus challenge; treatment continued for 4 days and dose (total dose, 25 mg). regimen suppressed symptoms until 48 after medication ceased, at time developed. another commenced challenge total...
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Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13(BN) rats possess substantial differences in blood pressure salt-sensitivity even with highly similar genetic backgrounds. The present study examined whether increased oxidative stress, particularly H2O2, the renal medulla of SS contributes to these differences. Blood was measured using femoral arterial catheters three groups rats: 1) 12-wk-old consomic fed a 0.4% NaCl diet, 2) 4% diet chronically infused saline or catalase (6.9...
BACKGROUND: Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery may be useful for treating delayed emergence, delirium, and postoperative cognitive dysfunction. Activation central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) anesthesia. Cholinergic neurons in brainstem basal forebrain are also known promote arousal....
Although general anesthetics are routinely administered to surgical patients induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness not fully understood. In rats, we characterized changes in extradural EEG and intracranial local field potentials (LFPs) within prefrontal cortex (PFC), parietal (PC), central thalamus (CT) response progressively higher doses inhaled anesthetic sevoflurane. During induction with a low dose sevoflurane, beta/low gamma (12-40...
NO synthase (NOS) can paradoxically contribute to the production of reactive oxygen species when l -arginine or cofactor R-tetrahydrobiopterin (BH 4 ) becomes limited. The present study examined whether NOS contributes superoxide in kidneys hypertensive Dahl salt-sensitive (SS) rats compared with an inbred consomic control strain (SS-13 BN and tested hypothesis that elevated dihydrobiopterin 2 levels are importantly involved this process. This was assessed by determining effects...
Many general anesthetics potentiate gamma-aminobutyric acid (GABA) A receptors but their neuroanatomic sites of action are less clear. GABAergic neurons in the rostromedial tegmental nucleus (RMTg) send inhibitory projections to multiple arousal-promoting nuclei, role these modulating consciousness is unknown. In this study, designer exclusively activated by drugs (DREADDs) were targeted RMTg Vgat-ires-Cre mice. DREADDs expression was found and other brainstem regions. Activation decreased...
Abstract A recently defined structure, the rostromedial tegmental nucleus (RMTg; aka tail of ventral area [VTA]), has been proposed as an inhibitory control center for dopaminergic activity VTA. This region is composed GABAergic cells that send afferent projections to midbrain and synapse onto in VTA substantia nigra. These exhibit µ-opioid receptor immunoreactivity, vivo, ex optogenetic/electrophysiological approaches demonstrate morphine excites dopamine neurons by targeting receptors on...
The achievement of reliability is a goal that must be pursued from the very beginning system design project. first step to consider each individual component used in and critically analyze its capabilities limitations. second project determine applications these components tend take advantage best avoid their worst This report lists brief analyses resulting have been made by staff Lincoln Laboratory over period several years. third final phase actual electronic circuit design, based on notes...