title: Reversal of established traumatic brain injury-induced, anxiety-like behavior in rats after delayed, post-injury neuroimmune suppression.
abstract: Abstract Traumatic brain injury (TBI) increases the risk of neuropsychiatric disorders, particularly anxiety disorders. Yet, there are presently no therapeutic interventions to prevent the development of post-traumatic anxiety or effective treatments once it has developed. This is because, in large part, of a lack of understanding of the underlying pathophysiology. Recent research suggests that chronic neuroinflammatory responses to injury may play a role in the development of post-traumatic anxiety in rodent models. Acute peri-injury administration of immunosuppressive compounds, such as Ibudilast (MN166), have been shown to prevent reactive gliosis associated with immune responses to injury and also prevent lateral fluid percussion injury (LFPI)-induced anxiety-like behavior in rats. There is evidence in both human and rodent studies that post-traumatic anxiety, once developed, is a chronic, persistent, and drug-refractory condition. In the present study, we sought to determine whether neuroinflammation is associated with the long-term maintenance of post-traumatic anxiety. We examined the efficacy of an anti-inflammatory treatment in decreasing anxiety-like behavior and reactive gliosis when introduced at 1 month after injury. Delayed treatment substantially reduced established LFPI-induced freezing behavior and reactive gliosis in brain regions associated with anxiety and continued neuroprotective effects were evidenced 6 months post-treatment. These results support the conclusion that neuroinflammation may be involved in the development and maintenance of anxiety-like behaviors after TBI.
authors.affiliation: 1 Department of Psychology and Neuroscience, University of Colorado , Boulder, Colorado.
authors.forename: Krista M
authors.initials: KM
authors.lastname: Rodgers
authors.forename: Yuetiva K
authors.initials: YK
authors.lastname: Deming
authors.forename: Florencia M
authors.initials: FM
authors.lastname: Bercum
authors.forename: Serhiy Y
authors.initials: SY
authors.lastname: Chumachenko
authors.forename: Julie L
authors.initials: JL
authors.lastname: Wieseler
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; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects*; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D016896:Treatment Outcome; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D007166:Immunosuppressive Agents; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles
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