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Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189.

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.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Reiner A,Heldt SA,Presley CS,Guley NH,Elberger AJ,Deng Y,D'Surney L,Rogers JT,Ferrell J,Bu W,Del Mar N,Honig MG,Gurley SN,Moore BM 2nd

doi

10.3390/ijms16010758

subject

Has Abstract

pub_date

2014-12-31 00:00:00

pages

758-87

issue

1

issn

1422-0067

pii

ijms16010758

journal_volume

16

pub_type

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