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Int. J. Mol. Sci. 2015, 16(1), 758-787; doi:10.3390/ijms16010758

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

1
Department of Anatomy and Neurobiology, the University of Tennessee Health Science Center, Memphis, TN 38163, USA
2
Department of Ophthalmology, the University of Tennessee Health Science Center, Memphis, TN 38163, USA
3
Department of Pharmaceutical Sciences, the University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Katalin Prokai-Tatrai
Received: 29 October 2014 / Accepted: 22 December 2014 / Published: 31 December 2014
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
View Full-Text   |   Download PDF [6385 KB, uploaded 31 December 2014]   |  

Abstract

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. View Full-Text
Keywords: TBI; deficits; microglia; CB2 receptors; therapy TBI; deficits; microglia; CB2 receptors; therapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Reiner, A.; Heldt, S.A.; Presley, C.S.; Guley, N.H.; Elberger, A.J.; Deng, Y.; D'Surney, L.; Rogers, J.T.; Ferrell, J.; Bu, W.; Del Mar, N.; Honig, M.G.; Gurley, S.N.; II, B.M.M. Motor, Visual and Emotional Deficits in Mice after Closed-Head Mild Traumatic Brain Injury Are Alleviated by the Novel CB2 Inverse Agonist SMM-189. Int. J. Mol. Sci. 2015, 16, 758-787.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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