Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain.
Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain.
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创伤性损伤导致幼年兔脑炎症和色氨酸代谢改变。
DOI：
10.1089/neu.2017.5450
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发表时间：
2018
影响因子：
4.2
通讯作者：
Zhi Zhang;L. Rasmussen;M. Saraswati;R. Koehler;C. Robertson;S. Kannan
中科院分区：
文献类型：
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作者：
Zhi Zhang;L. Rasmussen;M. Saraswati;R. Koehler;C. Robertson;S. Kannan
创伤性脑损伤（TBI）后的神经炎症导致广泛的细胞死亡和组织损失。在这里，我们在兔小儿TBI模型中评估了脑中的顺序炎症反应，以及炎症诱导的脑色氨酸代谢随时间的变化。在出生后5-7天（P5-P7），新西兰白兔窝仔随机分为三组：naïve（无损伤），假手术（单独开颅）和TBI（控制皮质冲击）。在损伤后6小时、1、3、7和21天处死动物，以评估促炎性和抗炎性细胞因子的水平，以及色氨酸-犬尿氨酸途径的主要成分。我们发现，1)损伤后脑区促炎性和抗炎性细胞因子水平存在时间依赖性的差异调节；2)吲哚胺2,3二氧合酶1 （IDO1）在损伤后21天持续升高；3)损伤后至少21天，TBI试剂盒损伤脑区血清素染色纤维的平均长度显著减少；4)伤后7 d犬尿氨酸水平显著升高。损伤后21天血清素/色氨酸比值和褪黑素/色氨酸比值显著下降，提示脑外伤后色氨酸代谢发生改变。更好地了解创伤性脑损伤后损伤和修复过程中免疫反应和色氨酸代谢的时间演变对于开发针对这些途径的新治疗策略至关重要。
Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: naïve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact). Animals were sacrificed at 6 h and 1, 3, 7, and 21 days post-injury for evaluating levels of pro- and anti-inflammatory cytokines, as well as the major components in the tryptophan-kynurenine pathway. We found that 1) pro- and anti-inflammatory cytokine levels in the brain injury area were differentially regulated in a time-dependent manner post-injury; 2) indoleamine 2,3 dioxygeenase 1 (IDO1) was upregulated around the injury area in TBI kits that persisted at 21 days post-injury; 3) mean length of serotonin-staining fibers was significantly reduced in the injured brain region in TBI kits for at least 21 days post-injury; and 4) kynurenine level significantly increased at 7 days post-injury. A significant decrease in serotonin/tryptophan ratio and melatonin/tryptophan ratio at 21 days post-injury was noted, suggesting that tryptophan metabolism is altered after TBI. A better understanding of the temporal evolution of immune responses and tryptophan metabolism during injury and repair after TBI is crucial for the development of novel therapeutic strategies targeting these pathways.