Motor, Visual and Emotional Deficits in Mice after Closed-Head Mild Traumatic Brain Injury Are Alleviated by the Novel CB2 Inverse Agonist SMM-189

International Journal of Molecular Sciences

Anton Reiner¹  Scott A. Heldt¹  Chaela S. Presley²  Natalie H. Guley¹  Andrea J. Elberger¹  Yunping Deng¹  Lauren D’Surney¹  Joshua T. Rogers¹  Jessica Ferrell¹  Wei Bu¹  Nobel Del Mar¹  Marcia G. Honig¹  Steven N. Gurley²  Bob M. Moore² 

[1] Department of Anatomy and Neurobiology, the University of Tennessee Health Science Center, Memphis, TN 38163, USA; E-Mails:;Department of Pharmaceutical Sciences, the University of Tennessee Health Science Center, Memphis, TN 38163, USA; E-Mails:

关键词: TBI;    deficits;    microglia;    CB2 receptors;    therapy;   

DOI  :  10.3390/ijms16010758

来源: mdpi

【 摘 要 】

We have developed a focal blast model of closed-head mild traumatic brain injury (TBI) in mice. As true for individuals that have experienced mild TBI, mice subjected to 50–60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2), we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50–60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.