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This study determined the effects of repeated treatment with a cannabinoid type 2 receptor (CB<jats:sub>2<\/jats:sub>R) agonist on blood\u2013brain barrier integrity, neuronal degeneration, and behavioral outcome in mice with TBI. We also looked for the presence of a prolonged treatment effect on the macrophage\/microglial response to injury. C57BL\/6 mice underwent controlled cortical impact (CCI) and received repeated treatments with a CB<jats:sub>2<\/jats:sub>R agonist, 0\u20101966, or vehicle. After euthanasia at 6 hr or 1, 2, 3, or 7 days postinjury, brains were removed for histochemical analysis. Blood\u2013brain barrier permeability changes were evaluated by using sodium fluorescein (NaF). Perilesional degenerating neurons, injury volumes, and macrophage\/microglia cells were quantified by stereological methods. Rota\u2010rod and open\u2010field testing were performed to evaluate motor function and natural exploratory behavior in mice. 0\u20101966 Treatment resulted in a significant reduction in NaF uptake and number of degenerating neurons compared with the vehicle\u2010treated group. 0\u20101966\u2010Treated mice demonstrated improvement on rota\u2010rod and open\u2010field testing compared with vehicle\u2010treated mice. These changes in CCI mice treated with 0\u20101966 were associated with a prolonged reduction in macrophage\/microglia cell counts. In conclusion, repeated treatments with a CB<jats:sub>2<\/jats:sub>R agonist, 0\u20101966, result in attenuated blood\u2013brain barrier disruption and neuronal degeneration. In addition, repeated treatment with 0\u20101966 shows prolonged treatment effects on behavior and the macrophage\/microglia cell response over several days. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23114","type":"journal-article","created":{"date-parts":[[2012,8,18]],"date-time":"2012-08-18T06:19:14Z","timestamp":1345270754000},"page":"2293-2305","source":"Crossref","is-referenced-by-count":97,"title":["A cannabinoid type 2 receptor agonist attenuates blood\u2013brain barrier damage and neurodegeneration in a murine model of traumatic brain injury"],"prefix":"10.1002","volume":"90","author":[{"given":"Peter S.","family":"Amenta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack I.","family":"Jallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald 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