Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions
Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions
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DOI：
10.1016/j.bbr.2016.10.041
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发表时间：
2018-03-15
影响因子：
2.7
通讯作者：
Standifer, Kelly M.
中科院分区：
文献类型：
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作者：
Awwad, Hibah O.;Durand, Cindy D.;Standifer, Kelly M.
由于攻击性运动和爆炸相关损伤，轻度创伤性脑损伤 (mTBI) 的诊断有所增加，但 mTBI 的细胞机制和病理学尚不完全清楚。先前的报道表明，Nociceptin Orphanin/FQ (N/OFQ) 是一种内源性神经肽，可导致机械性脑损伤后的损伤后缺血，但其在冲击波诱发 TBI 后的脑缺氧、前庭运动功能和损伤标志物表达中的具体作用尚不清楚。这项研究首次确定了 N/OFQ 及其 N/OFQ 肽 (NOP) 受体与雄性大鼠单次 80 psi 头部爆炸暴露后 TBI 引起的变化之间的直接关系。与假手术大鼠相比，TBI 后脑组织和血浆中的 N/OFQ 和 NOP 受体表达增加，同时发生前庭功能障碍，但先于缺氧和损伤标志物的出现。使用 NOP 受体拮抗剂 SB-612111 进行单次爆炸后治疗，可暂时改善急性前庭运动性能。它还可以防止 TBI 诱导的缺氧、促凋亡蛋白和爆炸后 8-10 天出现的损伤标记物的增加。这项研究揭示了 N/OFQ-NOP 受体系统在急变性 TBI 中的明显作用，并表明 NOP 受体拮抗剂对 mTBI 的潜在治疗用途。 (C)2016 Elsevier B.V. 保留所有权利。
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 80 psi 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, proapoptotic proteins and injury seen 8-10 days 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. (C)2016 Elsevier B.V. All rights reserved.