Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, Against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury

Journal of Neurotrauma
Xi-Chun May LuFrank C Tortella

Abstract

Post-traumatic seizures can exacerbate injurious outcomes of severe brain trauma, yet effective treatments are limited owing to the complexity of the pathology underlying the concomitant occurrence of both events. In this study, we tested C-10068, a novel deuterium-containing analog of (+)-N-methyl-3-ethoxymorphinan, in a rat model of penetrating ballistic-like brain injury (PBBI) and evaluated the effects of C-10068 on PBBI-induced nonconvulsive seizures (NCS), acute neuroinflammation, and neurofunctional outcomes. NCS were detected by electroencephalographic monitoring. Neuroinflammation was evaluated by immunohistochemical markers, for example, glial fibrillary acidic protein and major histocompatibility complex class I, for activation of astrocytes and microglia, respectively. Neurofunction was tested using rotarod and Morris water maze tasks. Three infusion doses of C-10068 (1.0, 2.5, and 5.0 mg/kg/h × 72 h) were tested in the antiseizure study. Neuroinflammation and neurofunction were evaluated in animals treated with 5.0 mg/kg/h × 72 h C-10068. Compared to vehicle treatment, C-10068 dose dependently reduced PBBI-induced NCS incidence (40-50%), frequency (20-70%), and duration (30-82%). The most effective antiseizure dose...Continue Reading

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Citations

Nov 7, 2015·Journal of Neurotrauma·Andrea MountneyDeborah Ann Shear
Aug 24, 2018·The Annals of Pharmacotherapy·Edward M Russak, Edward M Bednarczyk
Apr 30, 2017·The Journal of Trauma and Acute Care Surgery·Xi-Chun M LuFrank C Tortella
Dec 26, 2018·Translational Vision Science & Technology·David J ValentCatherine A Cukras
May 7, 2015·The Journal of Pharmacology and Experimental Therapeutics·Vinita UttamsinghRoger Tung

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BETA
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ImageJ
Inquiry Digital Analysis System
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Noldus EthoVision XT

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