Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization

Molly Braun, Zenab T. Khan, Mohammad B. Khan, Manish Kumar, Ayobami Ward, Bhagelu R. Achyut, Ali S. Arbab, David C. Hess, Md Nasrul Hoda, Babak Baban, Krishnan M. Dhandapani, Kumar Vaibhav

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Inflammation is an important mediator of secondary neurological injury after traumatic brain injury (TBI). Endocannabinoids, endogenously produced arachidonate based lipids, have recently emerged as powerful anti-inflammatory compounds, yet the molecular and cellular mechanisms underlying these effects are poorly defined. Endocannabinoids are physiological ligands for two known cannabinoid receptors, CB1R and CB2R. In the present study, we hypothesized that selective activation of CB2R attenuates neuroinflammation and reduces neurovascular injury after TBI. Using a murine controlled cortical impact (CCI) model of TBI, we observed a dramatic upregulation of CB2R within infiltrating myeloid cells beginning at 72 h. Administration of the selective CB2R agonist, GP1a (1–5 mg/kg), attenuated pro-inflammatory M1 macrophage polarization, increased anti-inflammatory M2 polarization, reduced edema development, enhanced cerebral blood flow, and improved neurobehavioral outcomes after TBI. In contrast, the CB2R antagonist, AM630, worsened outcomes. Taken together, our findings support the development of selective CB2R agonists as a therapeutic strategy to improve TBI outcomes while avoiding the psychoactive effects of CB1R activation.

Original languageEnglish (US)
Pages (from-to)224-237
Number of pages14
JournalBrain, Behavior, and Immunity
Volume68
DOIs
StatePublished - Feb 2018

Keywords

  • Cannabinoid receptor 2
  • Controlled cortical impact
  • Inflammation
  • Macrophage
  • Marijuana

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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