Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions

Publication date: 15 March 2018
Source:Behavioural Brain Research, Volume 340
Author(s): Hibah O. Awwad, Cindy D. Durand, Larry P. Gonzalez, Paul Tompkins, Yong Zhang, Megan R. Lerner, Daniel J. Brackett, David M. Sherry, Vibhudutta Awasthi, Kelly M. Standifer
Mild traumatic brain injury (mTBI) diagnoses have increased due to aggressive sports and blast-related injuries, but the cellular mechanisms and pathology underlying mTBI are not completely understood. Previous reports indicate that Nociceptin Orphanin/FQ (N/OFQ), an endogenous neuropeptide, contributes to post-injury ischemia following mechanical brain injury, yet its specific role in cerebral hypoxia, vestibulomotor function and injury marker expression following blast-induced TBI is not known. This study is the first to identify a direct association of N/OFQ and its N/OFQ peptide (NOP) receptor with TBI-induced changes following a single 80psi head blast exposure in male rats. N/OFQ and NOP receptor expression increased in brain tissue and plasma following TBI, concurrent with vestibular dysfunction but preceding hypoxia and appearance of injury markers compared to sham rats. A single post-blast treatment with the NOP receptor antagonist, SB-612111, transiently improved acute vestibulomotor performance. It also prevented increases in markers of TBI-induced hypoxia, pro-apoptotic proteins and injury seen 8–10days post-blast. This study reveals an apparent role for the N/OFQ-NOP receptor system in blast TBI and suggests potential therapeutic utility of NOP receptor antagonists for mTBI.

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