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.

• Authors: Marylou V Solbrig, Yijun Fan, Paul Hazelton
• Journal: Brain research (Brain Res) Vol. 1537 Pg. 273-82 (Nov 06 2013) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 24021420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Benzoxazines
• Cannabinoid Receptor Agonists
• Cannabinoids
• Morpholines
• Naphthalenes
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• Receptors, Cannabinoid
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
• HU 308

Topics

• Animals
• Benzoxazines (pharmacology)
• Cannabinoid Receptor Agonists (pharmacology)
• Cannabinoids (pharmacology, therapeutic use)
• Encephalitis, Viral (drug therapy, metabolism)
• Male
• Microglia (drug effects, metabolism)
• Morpholines (pharmacology)
• Naphthalenes (pharmacology)
• Rats
• Rats, Inbred Lew
• Receptor, Cannabinoid, CB1 (agonists)
• Receptor, Cannabinoid, CB2 (agonists)
• Receptors, Cannabinoid (metabolism)