Browsing by Author "Yang, L."

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    Magnetic-field-synchronized wireless modulation of neural activity by magnetoelectric nanoparticles
    (Elsevier, 2022) Zhang, E.; Abdel-Mottaleb, M.; Liang, P.; Navarrete, B.; Akin Yildirim, Y.; Alberteris Campos, M.; Smith, I. T.; Wang, P.; Yildirim, B.; Yang, L.; Chen, S.; Smith, I.; Lur, G.; Nguyen, T.; Jin, X.; Noga, B. R.; Ganzer, P.; Khizroev, S.; Anesthesia, School of Medicine
    The in vitro study demonstrates wirelessly controlled modulation of neural activity using magnetoelectric nanoparticles (MENPs), synchronized to magnetic field application with a sub-25-msec temporal response. Herein, MENPs are sub-30-nm CoFe2O4@BaTiO3 core-shell nanostructures. MENPs were added to E18 rat hippocampal cell cultures (0.5 μg of MENPs per 100,000 neurons) tagged with fluorescent Ca2+ sensitive indicator cal520. MENPs were shown to wirelessly induce calcium transients which were synchronized with application of 1200-Oe bipolar 25-msec magnetic pulses at a rate of 20 pulses/sec. The observed calcium transients were similar, in shape and magnitude, to those generated through the control electric field stimulation with a 50-μA current, and they were inhibited by the sodium channel blocker tetrodotoxin. The observed MENP-based magnetic excitation of neural activity is in agreement with the non-linear M - H hysteresis loop of the MENPs, wherein the MENPs' coercivity value sets the threshold for the externally applied magnetic field.
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    The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats
    (Elsevier, 2019) Witkin, Jeffrey M.; Cerne, R.; Davis, P. G.; Freeman, K. B.; do Carmo, J. M.; Rowlett, J. K.; Methuku, K. R.; Okun, A.; Gleason, S. D.; Krambis, M. J.; Poe, M.; Li, G.; Schkeryantz, J. M.; Jahan, R.; Yang, L.; Guo, W.; Golani, L. K.; Anderson, W. H.; Catlow, J. T.; Jones, T. M.; Porreca, F.; Smith, Jodi L.; Knopp, K. L.; Cook, J. M.; Neurological Surgery, School of Medicine
    Clinical evidence indicates that positive allosteric modulators (PAMs) of GABAA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABAA receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABAA receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvulsant, and antinociceptive effects in rodents with reduced motoric side effects. The present study evaluated the potential of KRM-II-81 as a novel analgesic. Oral administration of KRM-II-81 attenuated formalin-induced flinching; in contrast, diazepam was not active. KRM-II-81 attenuated nociceptive-associated behaviors engendered by chronic spinal nerve ligation (L5/L6). Diazepam decreased locomotion of rats at the dose tested in the formalin assay (10 mg/kg) whereas KRM-II-81 produced small decreases that were not dose-dependent (10–100 mg/kg). Plasma and brain levels of KRM-II-81 were used to demonstrate selectivity for α2/3- over α1-associated GABAA receptors and to define the degree of engagement of these receptors. Plasma and brain concentrations of KRM-II-81 were positively-associated with analgesic efficacy. GABA currents from isolated rat dorsal-root ganglion cultures were potentiated by KRM-II-81 with an ED50 of 32 nM. Measures of respiratory depression were reduced by alprazolam whereas KRM-II-81 was either inactive or produced effects with lower potency and efficacy. These findings add to the growing body of data supporting the idea that α2/3-selective GABAA receptor PAMs will have efficacy and tolerability as pain medications including those for neuropathic pain. Given their predicted anxiolytic effects, α2/3-selective GABAA receptor PAMs offer an additional inroad into the management of pain.