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      Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems

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          Abstract

          Neurochemical recording techniques have expanded our understanding of the pathophysiology of neurological disorders, as well as the mechanisms of action of treatment modalities like deep brain stimulation (DBS). DBS is used to treat diseases such as Parkinson’s disease, Tourette syndrome, and obsessive-compulsive disorder, among others. Although DBS is effective at alleviating symptoms related to these diseases and improving the quality of life of these patients, the mechanism of action of DBS is currently not fully understood. A leading hypothesis is that DBS modulates the electrical field potential by modifying neuronal firing frequencies to non-pathological rates thus providing therapeutic relief. To address this gap in knowledge, recent advances in electrochemical sensing techniques have given insight into the importance of neurotransmitters, such as dopamine, serotonin, glutamate, and adenosine, in disease pathophysiology. These studies have also highlighted their potential use in tandem with electrophysiology to serve as biomarkers in disease diagnosis and progression monitoring, as well as characterize response to treatment. Here, we provide an overview of disease-relevant neurotransmitters and their roles and implications as biomarkers, as well as innovations to the biosensors used to record these biomarkers. Furthermore, we discuss currently available neurochemical and electrophysiological recording devices, and discuss their viability to be implemented into the development of a closed-loop DBS system.

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          Electrode systems for continuous monitoring in cardiovascular surgery.

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            Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms.

            Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these effects. Dissociative, psychotomimetic, cognitive, and peripheral side effects associated with short-term or prolonged exposure, as well as recreational ketamine use, are also discussed. We further describe ketamine's pharmacokinetics, including its rapid and extensive metabolism to norketamine, dehydronorketamine, hydroxyketamine, and hydroxynorketamine (HNK) metabolites. Whereas the anesthetic and analgesic properties of ketamine are generally attributed to direct ketamine-induced inhibition of N-methyl-D-aspartate receptors, other putative lower-affinity pharmacological targets of ketamine include, but are not limited to, γ-amynobutyric acid (GABA), dopamine, serotonin, sigma, opioid, and cholinergic receptors, as well as voltage-gated sodium and hyperpolarization-activated cyclic nucleotide-gated channels. We examine the evidence supporting the relevance of these targets of ketamine and its metabolites to the clinical effects of the drug. Ketamine metabolites may have broader clinical relevance than was previously considered, given that HNK metabolites have antidepressant efficacy in preclinical studies. Overall, pharmacological target deconvolution of ketamine and its metabolites will provide insight critical to the development of new pharmacotherapies that possess the desirable clinical effects of ketamine, but limit undesirable side effects.
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              Deep brain stimulation: current challenges and future directions

              The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders. Despite the success and rapid adoption of DBS, crucial questions remain, including which brain areas should be targeted and in which patients. This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet challenges and future directions in the DBS field. Determining the next steps in DBS science will help to define the future role of this technology in the development of novel therapeutics for the most challenging disorders affecting the human brain.
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                Author and article information

                Journal
                101665910
                44233
                Rev Anal Chem
                Rev Anal Chem
                Reviews in analytical chemistry
                0793-0135
                2191-0189
                31 January 2021
                31 December 2020
                2020
                20 April 2021
                : 39
                : 1
                : 188-199
                Affiliations
                [1 ]Department of Neurosurgery Research, Mayo Clinic, Rochester, MN 55902, United States
                [2 ]Medical Scientist Training Program, Mayo Clinic, Rochester, MN 55902, United States
                [3 ]Division of Engineering, Mayo Clinic, Rochester, MN 55902, United States
                [4 ]Department of Biomedical Engineering, Mayo Clinic, Rochester, MN, 55902, United States
                Author notes
                [#]

                These authors contributed equally to this work

                [* ] Corresponding author: Oh.Yoonbae@ 123456mayo.edu
                Article
                NIHMS1667022
                10.1515/revac-2020-0117
                8057673
                33883813
                ac88b3f0-a51c-4d32-a1c6-6b9c63e100a6

                This work is licensed under the Creative Commons Attribution 4.0 International License.

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                deep brain stimulation,neuromodulation,electrochemistry,electrophysiology,closed-loop,voltammetry

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