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Prospects for cannabinoid therapies in viral encephalitis.

Abstract

Cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. Whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the CNS is not known. Using a rodent model of chronic viral encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective (Solbrig et al., 2010), we examine longer term (2 week treatment) effects of a general (CB1 and CB2) cannabinoid receptor agonist WIN55,212-2 (1mg/kg ip twice per day) or a specific (CB2) cannabinoid receptor agonist HU-308 (5mg/kg ip once daily) on histopathology, measures of frontostriatal neurogenesis and gliogenesis, and viral load. We find that WIN and HU-308 differ in their ability to protect new BrdU(+) cells. The selective CB2 agonist HU increases BrdU(+) cells in prefrontal cortex (PFC), significantly increases BrdU(+) cells in striatum, differentially regulates polydendrocytes vs. microglia/macrophages, and reduces immune activation at a time WIN-treated rats appear tolerant to the anti-inflammatory effect of their cannabinoid treatment. WIN and HU had little direct viral effect in PFC and striatum, yet reduced viral signal in hippocampus. Thus, HU-308 action on CB2 receptors, receptors known to be renewed during microglia proliferation and action, is a nontolerizing mechanism of controlling CNS inflammation during viral encephalitis by reducing microglia activation, as well as partially limiting viral infection, and uses a nonpsychotropic cannabinoid agonist.

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  • Authors+Show Affiliations

    ,

    Department of Medicine (Neurology), University of Manitoba, Winnipeg, MB, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. Electronic address: msolbrig2@hsc.mb.ca.

    ,

    Source

    Brain research 1537: 2013 Nov 06 pg 273-82

    MeSH

    Animals
    Benzoxazines
    Cannabinoid Receptor Agonists
    Cannabinoids
    Encephalitis, Viral
    Male
    Microglia
    Morpholines
    Naphthalenes
    Rats
    Rats, Inbred Lew
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Receptors, Cannabinoid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24021420

    Citation

    Solbrig, Marylou V., et al. "Prospects for Cannabinoid Therapies in Viral Encephalitis." Brain Research, vol. 1537, 2013, pp. 273-82.
    Solbrig MV, Fan Y, Hazelton P. Prospects for cannabinoid therapies in viral encephalitis. Brain Res. 2013;1537:273-82.
    Solbrig, M. V., Fan, Y., & Hazelton, P. (2013). Prospects for cannabinoid therapies in viral encephalitis. Brain Research, 1537, pp. 273-82. doi:10.1016/j.brainres.2013.08.032.
    Solbrig MV, Fan Y, Hazelton P. Prospects for Cannabinoid Therapies in Viral Encephalitis. Brain Res. 2013 Nov 6;1537:273-82. PubMed PMID: 24021420.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Prospects for cannabinoid therapies in viral encephalitis. AU - Solbrig,Marylou V, AU - Fan,Yijun, AU - Hazelton,Paul, Y1 - 2013/09/07/ PY - 2013/05/20/received PY - 2013/07/25/revised PY - 2013/08/17/accepted PY - 2013/9/12/entrez PY - 2013/9/12/pubmed PY - 2014/6/26/medline KW - Borna Disease virus KW - Cannabinoid type-2 receptor KW - Rat SP - 273 EP - 82 JF - Brain research JO - Brain Res. VL - 1537 N2 - Cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. Whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the CNS is not known. Using a rodent model of chronic viral encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective (Solbrig et al., 2010), we examine longer term (2 week treatment) effects of a general (CB1 and CB2) cannabinoid receptor agonist WIN55,212-2 (1mg/kg ip twice per day) or a specific (CB2) cannabinoid receptor agonist HU-308 (5mg/kg ip once daily) on histopathology, measures of frontostriatal neurogenesis and gliogenesis, and viral load. We find that WIN and HU-308 differ in their ability to protect new BrdU(+) cells. The selective CB2 agonist HU increases BrdU(+) cells in prefrontal cortex (PFC), significantly increases BrdU(+) cells in striatum, differentially regulates polydendrocytes vs. microglia/macrophages, and reduces immune activation at a time WIN-treated rats appear tolerant to the anti-inflammatory effect of their cannabinoid treatment. WIN and HU had little direct viral effect in PFC and striatum, yet reduced viral signal in hippocampus. Thus, HU-308 action on CB2 receptors, receptors known to be renewed during microglia proliferation and action, is a nontolerizing mechanism of controlling CNS inflammation during viral encephalitis by reducing microglia activation, as well as partially limiting viral infection, and uses a nonpsychotropic cannabinoid agonist. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/24021420/Prospects_for_cannabinoid_therapies_in_viral_encephalitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(13)01169-4 DB - PRIME DP - Unbound Medicine ER -