171 research outputs found

    Elevated extracellular potassium ion concentrations suppress hippocampal oscillations in a mouse model of Dravet syndrome in-vitro

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    Background: Hippocampal hyperexcitability and seizure-like events have been consistently demonstrated in hippocampal slice preparations perfused with ≥ 5 mM high [K+] artificial cerebrospinal fluid (ACSF). Accordingly, high [K+] ACSF has been effectively employed as ionic model of seizure for in vitro experiments, but then, how reliable is this model when employed for in-vitro studies of brain tissues with dysregulated K+ homeostasis? To address this question, we examined how elevations of [K+]o affect hippocampal oscillations in Scn1a mutant mouse, a mouse model of Dravet syndrome, a devastating genetic-epilepsy associated with gliosis, a major cause of dysregulated K+ homeostasis in epileptic brain.Methods: To this end, performing local field potential (LFP) recordings from hippocampi of P30 to P38 Scn1a mutant mice (Scn1a +/-) and wild-type littermates (Scn1a +/+), maintained on a C57BL/6 genetic background, in brain slice preparations in normal and high K+ conditions, we studied the effect of 4 mM and 5 mM high [K+] ACSF(s) on hippocampal oscillations.Results: Hippocampal hyperexcitability was observed only in Scn1a +/+ but not in Scn1a +/- mice. In Scn1a +/- mice, spontaneous hippocampal hyperexcitability was observed in normal ACSF but was significantly suppressed by 4 mM and 5 mM high [K+] ACSF(s).Conclusion: In conclusion, these findings, for the first time, provide evidence of spontaneous hippocampal activity in Scn1a+/- mice older than P30 which may be potentially used as a target for screening anti-epileptic approaches, beneficial for the treatment of DS. Elevated [K+]o-induced depolarization block of neuronal action potentials is involved in epileptic brain tissues modulated in elevated [K+]o. This mechanism underlies the suppressing effect of high [K+] ACSF on hippocampal oscillations in Scn1a+/- mice in vitro. Future studies employing the high K+ ionic model for studies of epileptic brain tissues are required to determine how K+ homeostasis is handled by neurons and glial cells in epileptic brain tissues.Keywords: Dravet syndrome, artificial cerebrospinal fluid (ACSF), Scn1a mutant mouse, depolarization bloc

    Spectroscopic And Computational Studies Of The Laser Photolysis Of Matrix Isolated 1,2-dibromoethanes: Formation And Fate Of The Bromoethyl Radicals

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    We report experimental and computational studies of the photolysis of atmospherically important 1,2-dibromoethanes (1,2-C(2)X(4)Br(2); X = H, F) in Ar matrixes at 5 K. Using the pulsed deposition method, we find that significant conformational relaxation occurs for 1,2-C(2)H(4)Br(2) (EDB; observed anti/gauche ratio =30:1) but not for 1,2-C(2)F(4)Br(2) (TFEDB; anti/gauche = 3:1), which is traced to a larger barrier to rotation about the C-C bond in the latter. Laser photolysis of matrix-isolated EDB at 220 nm reveals the growth of infrared bands assigned to the gauche conformer and C(2)H(4)-Br(2) charge transfer complex (both as major products), and the C(2)H(4)Br radical and C(2)H(3)Br-HBr complex as minor (trace) products. The presence of the C(2)H(4)-Br(2) complex is confirmed in the UV/visible spectrum, which shows an intense charge transfer band at 237 nm that grows in intensity upon annealing. In contrast to previous reports, our experimental and computational results do not support a bridged structure for the C(2)H(4)Br radical in either the gas phase or matrix environments. We also report on the laser photolysis of matrix-isolated TFEDB at 220 nm. Here, the dominant photoproducts are the anti and gauche conformers of the C(2)F(4)Br radical, the vibrational and electronic spectra of which are characterized here for the first time. The increase in yield of radical for TFEDB vs EDB is consistent with the stronger C-Br bond in the fluoro-substituted radical species. The photochemistry of the C(2)F(4)Br radical following excitation at 266 nm was investigated and found to lead C-Br bond cleavage and formation of C(2)F(4). The implications of this work for the atmospheric and condensed phase photochemistry of the alkyl halides is emphasized

    Sonography of Morelâ Lavallée Lesions

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135423/1/jum20082771077.pd

    Matrix Isolation and Computational Study of Isodifluorodibromomethane (F2 Cbr-Br): A Route to Br2 Formation in Cf2 Br2 Photolysis

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    The photolysis products of dibromodifluoromethane (CF2 Br 2) were characterized by matrix isolation infrared and UV/Visible spectroscopy, supported by ab initio calculations. Photolysis at wavelengths of 240 and 266 nm of CF2 Br2:Ar samples (∼1:5000) held at ∼5 K yielded iso- CF2 Br2 (F2 CBrBr), a weakly bound isomer of CF2 Br2, which is characterized here for the first time. The observed infrared and UV/Visible absorptions of iso- CF2 Br2 are in excellent agreement with computational predictions at the B3LYP/aug-cc-pVTZ level. Single point energy calculations at the CCSD(T)/aug-cc-pVDZ level on the B3LYP optimized geometries suggest that the isoform is a minimum on the CF2 Br2 potential energy surface, lying some 55 kcal/mol above the CF2 Br2 ground state. The energies of various stationary points on the CF2 Br 2 potential energy surface were characterized computationally; taken with our experimental results, these show that iso- CF2 Br 2 is an intermediate in the Br+ CF2 Br→ CF 2 + Br2 reaction. The photochemistry of the isoform was also investigated; excitation into the intense 359 nm absorption band resulted in isomerization to CF2 Br2. Our results are discussed in view of the rich literature on the gas-phase photochemistry of CF2 Br2, particularly with respect to the existence of a roaming atom pathway leading to molecular products. © 2010 American Institute of Physics

    Ultrasound Features of Palmar Fibromatosis or Dupuytren Contracture

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147818/1/jum14699_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147818/2/jum14699.pd
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