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Prospects for cannabinoid therapies in viral encephalitis.
Brain Res 2013; 1537:273-82BR

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.

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.No affiliation info availableNo affiliation info available

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 -