Kawa Lizan, Arborelius Ulf P, Yoshitake Takashi, Kehr Jan, Hökfelt Tomas, Risling Mårten, Agoston Denes
1 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
2 Department of Physiology and Pharmacology, Karolinska Institutet , Stockholm, Sweden .
J Neurotrauma. 2015 Aug 15;32(16):1190-9. doi: 10.1089/neu.2014.3669. Epub 2015 Apr 1.
Exposure to improvised explosive devices can result in a unique form of traumatic brain injury--blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.
接触简易爆炸装置可导致一种独特形式的创伤性脑损伤——爆炸所致创伤性脑损伤(bTBI)。在症状较轻的一端(轻度bTBI [mbTBI]),会出现认知和情绪障碍。在因暴露于极端心理压力而非身体损伤所致的创伤后应激障碍中也观察到了类似症状。单胺能系统在情绪调节和应激中的作用已得到充分证实,但其在mbTBI中的作用尚不清楚。为填补这一空白,我们使用了mbTBI的啮齿动物模型,发现在暴露后1天的强迫游泳试验中不动行为减少,同时攀爬行为增加,但在14天及以后则没有,这可能表明焦虑样行为短暂增加。通过原位杂交,我们发现早在暴露后2小时,蓝斑核和中缝背核中酪氨酸羟化酶和色氨酸羟化酶2的信使核糖核酸水平就分别升高。暴露后1天的高效液相色谱分析主要显示几个前脑区域的去甲肾上腺素水平升高。综上所述,我们报告轻度爆炸暴露会导致焦虑样行为和脑区特异性分子变化的短暂改变,这表明单胺能系统参与了mbTBI的病理生物学过程。