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

Anton Reiner, Scott Heldt, Chaela S. Presley, Natalie H. Guley, Andrea J. Elberger, Yunping Deng, Lauren D'Surney, Joshua T. Rogers, Jessica Ferrell, Wei Bu, Nobel Del Mar, Marcia Honig, Steven N. Gurley, Bob Moore

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)758-787
Number of pages30
JournalInternational journal of molecular sciences
Volume16
Issue number1
DOIs
StatePublished - Dec 31 2015

Fingerprint

Brain Concussion
brain damage
mice
Brain
Head
blasts
Cannabinoid Receptor CB2
Microglia
Chemical activation
activation
phenotype
Diffuse Axonal Injury
Phenotype
Brain Injuries
Cannabinoids
healing
SMM-189
neurons
Neurons
evaluation

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189. / Reiner, Anton; Heldt, Scott; Presley, Chaela S.; Guley, Natalie H.; Elberger, Andrea J.; Deng, Yunping; D'Surney, Lauren; Rogers, Joshua T.; Ferrell, Jessica; Bu, Wei; Del Mar, Nobel; Honig, Marcia; Gurley, Steven N.; Moore, Bob.

In: International journal of molecular sciences, Vol. 16, No. 1, 31.12.2015, p. 758-787.

Research output: Contribution to journalArticle

Reiner, Anton ; Heldt, Scott ; Presley, Chaela S. ; Guley, Natalie H. ; Elberger, Andrea J. ; Deng, Yunping ; D'Surney, Lauren ; Rogers, Joshua T. ; Ferrell, Jessica ; Bu, Wei ; Del Mar, Nobel ; Honig, Marcia ; Gurley, Steven N. ; Moore, Bob. / Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189. In: International journal of molecular sciences. 2015 ; Vol. 16, No. 1. pp. 758-787.
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