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Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus

OBJECTIVE: C57BL/6J mice infected with Theiler's murine encephalomyelitis virus (TMEV) develop acute behavioral seizures in the first week of infection and later develop chronic epilepsy. The TMEV model provides a useful platform to test novel antiseizure therapeutics. The present study was des...

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Autores principales: Patel, Dipan C., Wallis, Glenna, Fujinami, Robert S., Wilcox, Karen S., Smith, Misty D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698680/
https://www.ncbi.nlm.nih.gov/pubmed/31440724
http://dx.doi.org/10.1002/epi4.12351
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author Patel, Dipan C.
Wallis, Glenna
Fujinami, Robert S.
Wilcox, Karen S.
Smith, Misty D.
author_facet Patel, Dipan C.
Wallis, Glenna
Fujinami, Robert S.
Wilcox, Karen S.
Smith, Misty D.
author_sort Patel, Dipan C.
collection PubMed
description OBJECTIVE: C57BL/6J mice infected with Theiler's murine encephalomyelitis virus (TMEV) develop acute behavioral seizures in the first week of infection and later develop chronic epilepsy. The TMEV model provides a useful platform to test novel antiseizure therapeutics. The present study was designed to test the efficacy of cannabidiol (CBD) in reducing acute seizures induced by viral infection. METHODS: C57BL/6J mice were infected intracortically with 2 × 10(5) plaque‐forming units of TMEV. Mice were divided into two treatment groups—1) CBD‐treated mice and 2) vehicle‐treated mice. Frequency and severity of acute seizures were evaluated by video‐monitoring the mice four times daily by the experimenter blinded to the treatment group. RESULTS: Cannabidiol (180 mg/kg; 360 mg/kg/day) decreased both the frequency and severity of acute behavioral seizures following TMEV infection, but 150 mg/kg of CBD did not improve overall seizure outcome. The time to peak effect (TPE) of CBD in the 6 Hz 32 mA psychomotor seizure test using C57BL/6J mice was observed at 2 hours post‐CBD treatment. Interestingly, CBD (150 mg/kg) significantly reduced frequency and severity of TMEV‐induced acute seizures at 2 hours post‐CBD treatment. These results suggest that CBD could be effective in decreasing TMEV‐induced acute seizures when the seizure test is conducted at the TPE of CBD. SIGNIFICANCE: Cannabinoids are increasingly studied for their potential antiseizure effects. Several preclinical and clinical studies provide evidence that CBD could be an effective therapy for intractable epilepsies. The present study corroborates those previous findings and provides an opportunity to investigate pharmacokinetics, pharmacodynamics, and mechanism(s) of antiseizure effects of CBD in the TMEV model, which may help to design future clinical studies more effectively.
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spelling pubmed-66986802019-08-22 Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus Patel, Dipan C. Wallis, Glenna Fujinami, Robert S. Wilcox, Karen S. Smith, Misty D. Epilepsia Open Full‐length Original Research OBJECTIVE: C57BL/6J mice infected with Theiler's murine encephalomyelitis virus (TMEV) develop acute behavioral seizures in the first week of infection and later develop chronic epilepsy. The TMEV model provides a useful platform to test novel antiseizure therapeutics. The present study was designed to test the efficacy of cannabidiol (CBD) in reducing acute seizures induced by viral infection. METHODS: C57BL/6J mice were infected intracortically with 2 × 10(5) plaque‐forming units of TMEV. Mice were divided into two treatment groups—1) CBD‐treated mice and 2) vehicle‐treated mice. Frequency and severity of acute seizures were evaluated by video‐monitoring the mice four times daily by the experimenter blinded to the treatment group. RESULTS: Cannabidiol (180 mg/kg; 360 mg/kg/day) decreased both the frequency and severity of acute behavioral seizures following TMEV infection, but 150 mg/kg of CBD did not improve overall seizure outcome. The time to peak effect (TPE) of CBD in the 6 Hz 32 mA psychomotor seizure test using C57BL/6J mice was observed at 2 hours post‐CBD treatment. Interestingly, CBD (150 mg/kg) significantly reduced frequency and severity of TMEV‐induced acute seizures at 2 hours post‐CBD treatment. These results suggest that CBD could be effective in decreasing TMEV‐induced acute seizures when the seizure test is conducted at the TPE of CBD. SIGNIFICANCE: Cannabinoids are increasingly studied for their potential antiseizure effects. Several preclinical and clinical studies provide evidence that CBD could be an effective therapy for intractable epilepsies. The present study corroborates those previous findings and provides an opportunity to investigate pharmacokinetics, pharmacodynamics, and mechanism(s) of antiseizure effects of CBD in the TMEV model, which may help to design future clinical studies more effectively. John Wiley and Sons Inc. 2019-07-19 /pmc/articles/PMC6698680/ /pubmed/31440724 http://dx.doi.org/10.1002/epi4.12351 Text en © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full‐length Original Research
Patel, Dipan C.
Wallis, Glenna
Fujinami, Robert S.
Wilcox, Karen S.
Smith, Misty D.
Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus
title Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus
title_full Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus
title_fullStr Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus
title_full_unstemmed Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus
title_short Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus
title_sort cannabidiol reduces seizures following cns infection with theiler's murine encephalomyelitis virus
topic Full‐length Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698680/
https://www.ncbi.nlm.nih.gov/pubmed/31440724
http://dx.doi.org/10.1002/epi4.12351
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