Startle suppression after mild traumatic brain injury is associated with an increase in pro-inflammatory cytokines, reactive gliosis and neuronal loss in the caudal pontine reticular nucleus
Startle suppression after mild traumatic brain injury is associated with an increase in pro-inflammatory cytokines, reactive gliosis and neuronal loss in the caudal pontine reticular nucleus
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DOI：
10.1016/j.bbi.2017.01.006
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发表时间：
2017-03-01
影响因子：
15.1
通讯作者：
Pang, Kevin C. H.
中科院分区：
文献类型：
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作者：
Sinha, Swamini P.;Avcu, Pelin;Pang, Kevin C. H.
轻度创伤性脑损伤（mTBI）可产生躯体症状，如头痛、头晕、疲劳、睡眠障碍和感觉运动功能障碍。感觉运动功能可以通过声音惊吓反射（ASR）等测试来测量，这是一种进化上保守的对短暂而尖锐的声音刺激的防御反应。mTBI在啮齿动物和人类中产生对ASR的持久抑制;然而，这种抑制的机制尚不清楚。本研究探讨了脑干（特别是脑桥尾侧网状核，PnC）的炎症过程是否可以解释mTBI后ASR的抑制，因为PnC是ASR回路的重要核。此外，虽然mTBI后的炎症通常在靠近撞击部位的脑区（皮质和海马）中观察到，但mTBI在脑干结构中的影响在很大程度上仍未得到充分研究。本研究证实了在损伤后一天ASR的抑制，并且在mTBI后持续至少三周，复制了先前的发现。在PnC内，在损伤后1天观察到IL-1 β和TNF-α mRNA的瞬时升高，而IL-1 α mRNA在损伤后3周表现出延迟的增加。分别在损伤后1天和7天，在PnC中也观察到反应性胶质增生（通过小胶质细胞的IBA-1-ir和星形胶质细胞的GFAP-ir）。最后，巨神经元（PnC中的主要功能细胞群）的数量在损伤后三周减少。结果表明，神经胶质细胞激活先于PnC中的神经元损失，并且与ASR的行为抑制相关。研究结果也暗示脑干参与创伤后症状的发展。(C)2017爱思唯尔公司All rights reserved.
Mild traumatic brain injury (mTBI) can produce somatic symptoms such as headache, dizziness, fatigue, sleep disturbances and sensorimotor dysfunction. Sensorimotor function can be measured by tests such as the acoustic startle reflex (ASR), an evolutionarily conserved defensive response to a brief yet sharp acoustic stimulus. mTBI produces a long-lasting suppression of ASR in rodents and humans; however, the mechanism of this suppression is unknown. The present study examined whether inflammatory processes in the brainstem (particularly the caudal pontine reticular nucleus, PnC) could account for the suppression of ASR after mTBI, because the PnC is an essential nucleus of the ASR circuit. Furthermore, while inflammation after mTBI is commonly observed in brain regions proximal to the site of impact (cortex and hippocampus), the effects of mTBI in brainstem structures remains largely understudied. The present study demonstrated a suppression of ASR one day after injury and lasting at least three weeks after an mTBI, replicating previous findings. Within the PnC, transient elevations of IL-1 beta and TNF-alpha mRNA were observed at one day after injury, while IL-1 alpha mRNA exhibited a delayed increase at three weeks after injury. Reactive gliosis (via IBA-1-ir for microglia and GFAP-ir for astrocytes) were also observed in the PnC, at one day and seven days after injury, respectively. Finally, the number of giant neurons (the major functional cell population in the PnC) was decreased three weeks after injury. The results indicate that glial activation precedes neuronal loss in the PnC, and correlates with the behavioral suppression of the ASR. The results also raise implications for brainstem involvement in the development of post traumatic symptoms. (C) 2017 Elsevier Inc. All rights reserved.