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Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization.
Brain Behav Immun 2018; 68:224-237BB

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.

Authors+Show Affiliations

Department of Neurosurgery, Medical College of Georgia, Augusta University, United States.Department of Neurosurgery, Medical College of Georgia, Augusta University, United States; Center for Nursing Research, Augusta University, United States.Department of Neurology, Medical College of Georgia, Augusta University, United States.European Molecular Biology Laboratory (EMBL), Monterontondo, Italy.Department of Neurosurgery, Medical College of Georgia, Augusta University, United States.Georgia Cancer Center, Augusta University, United States.Georgia Cancer Center, Augusta University, United States.Department of Neurology, Medical College of Georgia, Augusta University, United States.Department of Neurology, Medical College of Georgia, Augusta University, United States; Department of Medical Laboratory, Imaging, and Radiological Sciences, College of Allied Health Sciences, Augusta University, United States.Department of Neurology, Medical College of Georgia, Augusta University, United States; Department of Oral Biology, Dental College of Georgia, Augusta University, United States; Department of Surgery, Medical College of Georgia, Augusta University, United States.Department of Neurosurgery, Medical College of Georgia, Augusta University, United States.Department of Neurosurgery, Medical College of Georgia, Augusta University, United States; Department of Medical Laboratory, Imaging, and Radiological Sciences, College of Allied Health Sciences, Augusta University, United States. Electronic address: kvaibhav@augusta.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29079445

Citation

Braun, Molly, et al. "Selective Activation of Cannabinoid Receptor-2 Reduces Neuroinflammation After Traumatic Brain Injury Via Alternative Macrophage Polarization." Brain, Behavior, and Immunity, vol. 68, 2018, pp. 224-237.
Braun M, Khan ZT, Khan MB, et al. Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization. Brain Behav Immun. 2018;68:224-237.
Braun, M., Khan, Z. T., Khan, M. B., Kumar, M., Ward, A., Achyut, B. R., ... Vaibhav, K. (2018). Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization. Brain, Behavior, and Immunity, 68, pp. 224-237. doi:10.1016/j.bbi.2017.10.021.
Braun M, et al. Selective Activation of Cannabinoid Receptor-2 Reduces Neuroinflammation After Traumatic Brain Injury Via Alternative Macrophage Polarization. Brain Behav Immun. 2018;68:224-237. PubMed PMID: 29079445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization. AU - Braun,Molly, AU - Khan,Zenab T, AU - Khan,Mohammad B, AU - Kumar,Manish, AU - Ward,Ayobami, AU - Achyut,Bhagelu R, AU - Arbab,Ali S, AU - Hess,David C, AU - Hoda,Md Nasrul, AU - Baban,Babak, AU - Dhandapani,Krishnan M, AU - Vaibhav,Kumar, Y1 - 2017/10/24/ PY - 2017/07/08/received PY - 2017/10/14/revised PY - 2017/10/23/accepted PY - 2017/10/29/pubmed PY - 2019/3/13/medline PY - 2017/10/29/entrez KW - Cannabinoid receptor 2 KW - Controlled cortical impact KW - Inflammation KW - Macrophage KW - Marijuana SP - 224 EP - 237 JF - Brain, behavior, and immunity JO - Brain Behav. Immun. VL - 68 N2 - 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. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/29079445/Selective_activation_of_cannabinoid_receptor_2_reduces_neuroinflammation_after_traumatic_brain_injury_via_alternative_macrophage_polarization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(17)30477-4 DB - PRIME DP - Unbound Medicine ER -