The striatum is infected later than PFC and hippocampus (Solbrig et al., 1994 and Solbrig et al., 1998), has less neovascularization and tissue remodeling (Solbrig et al., 2010), and similar viral quantification across groups in this study. We see “same virus, more pathology”, for example, increased ED1 staining per microscopic field in

striatum of WIN selleck inhibitor and BD rats compared to HU-treated rats. Thus, in striatum, a structure normalized for virus, degree of inflammatory neuropathology is a reflection of anti-inflammatory efficacy of a drug treatment, not virus. In PFC, where neuropathology appears more advanced and vRNA numbers more divergent, there was no clear association between virus and either pro- or anti-inflammatory effects across the 3 groups. And finally, in hippocampus, HU produced a modest reduction in vRNA, with the mechanism of effect on virus not known. The multiple factors involved selleck kinase inhibitor in Borna Disease expression and progression under cannabinoid treatment cannot be completely reconciled using a single in vivo system, and a systematic approach integrated across several experimental domains will be required. Our current results introduce

the possibility that CB2 R agonist-induced changes at cellular, tissue, or systems level could have a role in reducing productive infections by BDV, may be generalizable to other neurotropic viruses, and provide a mechanism of neuroprotection beyond reduction of inflammation. Our results also improve upon past trials managing BDV encephalitis in rats with aggressive immunosuppressive therapy that resulted in dissemination and unusual distribution of virus beyond the CNS (Stitz et al., 1991). In summary, upregulation of CB2 expression under different pathophysiological conditions has been reported in several experimental paradigms and disease states with inflammatory or degenerative processes, diseases that have in common

glial activation, inflammation, oxidative/nitrative stress, and degeneration. Targeting of CB2 receptors with selective agonists is a new therapeutic avenue in inflammatory degenerative disorders for reduction of neuroinflammation. Our experiments show HU-308 activation of CB2 receptors, receptors known to be renewed Sclareol during microglia proliferation and action, is a nontolerizing mechanism of controlling CNS inflammation during viral encephalitis and uses a nonpsychotropic cannabinoid agonist. Contrast with WIN will help inform decisions in use of newly developed cannabinoid agonists as accessory therapy. Male Lewis rats (Charles River Labs, Wilmington, MA, USA) were group housed on a 12 h light–dark cycle with ad libitum access to food and water. All experimental procedures were performed in compliance with the institutional (University of Manitoba) and Policy for the Humane Care and Use of Laboratory Animals guidelines.