title: Acute neuroimmune modulation attenuates the development of anxiety-like freezing behavior in an animal model of traumatic brain injury.
abstract: Chronic anxiety is a common and debilitating result of traumatic brain injury (TBI) in humans. While little is known about the neural mechanisms of this disorder, inflammation resulting from activation of the brain's immune response to insult has been implicated in both human post-traumatic anxiety and in recently developed animal models. In this study, we used a lateral fluid percussion injury (LFPI) model of TBI in the rat and examined freezing behavior as a measure of post-traumatic anxiety. We found that LFPI produced anxiety-like freezing behavior accompanied by increased reactive gliosis (reflecting neuroimmune inflammatory responses) in key brain structures associated with anxiety: the amygdala, insula, and hippocampus. Acute peri-injury administration of ibudilast (MN166), a glial cell activation inhibitor, suppressed both reactive gliosis and freezing behavior, and continued neuroprotective effects were apparent several months post-injury. These results support the conclusion that inflammation produced by neuroimmune responses to TBI play a role in post-traumatic anxiety, and that acute suppression of injury-induced glial cell activation may have promise for the prevention of post-traumatic anxiety in humans.
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado-Boulder, Boulder, CO 80309, USA.
authors.forename: Krista M
authors.initials: KM
authors.lastname: Rodgers
authors.forename: Florencia M
authors.initials: FM
authors.lastname: Bercum
authors.forename: Danielle L
authors.initials: DL
authors.lastname: McCallum
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Rudy
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Frey
authors.forename: Kirk W
authors.initials: KW
authors.lastname: Johnson
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Barth
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000523:psychology*; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects* / Q000502:physiology; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007155:Immunologic Factors