Application of the Zebrafish Traumatic Brain Injury Model in Assessing Cerebral Inflammation
Application of the Zebrafish Traumatic Brain Injury Model in Assessing Cerebral Inflammation
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斑马鱼脑外伤模型在脑炎症评估中的应用
DOI：
10.1089/zeb.2019.1793
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发表时间：
2020-04-01
期刊：
影响因子：
2
通讯作者：
Zhang, Jingjing
中科院分区：
文献类型：
--
作者：
Gan, Daqing;Wu, Shuilong;Zhang, Jingjing
创伤性脑损伤（TBI）是一个重大的公共和社会经济问题在世界各地。建立一个有效的和具有成本效益的TBI模型开发新的治疗药物是具有挑战性的。小胶质细胞被认为是中枢神经系统（CNS）的常驻巨噬细胞，通常不进入大脑。小胶质细胞作为中枢神经系统先天性免疫反应的主要介质，在创伤性脑损伤后的神经炎症和继发性损伤中发挥重要作用。在这项研究中，我们建立了一个在体内TBI斑马鱼模型使用Tg（coro 1a：EGFP）线，其中的绿色荧光蛋白标记的小胶质细胞存在。我们证明了小胶质细胞在神经元损伤后迅速积累。为了清除受损的神经元并恢复CNS稳态，活化的小胶质细胞分泌两种类型的功能性细胞因子，包括损伤幼虫中的促炎性白细胞介素（IL）IL-1 β和IL-6以及抗炎因子IL-4和IL-10。胞苷5 '-二磷酸胆碱（Cytidine 5 '-Diphosphocholine，CDP-choline）作为一种有效的临床神经保护药物，可进一步激活小胶质细胞，在TBI模型中表达高水平的IL-1 β、IL-6、IL-4和IL-10。此外，CDP-胆碱减少神经细胞凋亡，促进损伤部位周围的神经细胞增殖。基于这些结果，本研究中建立的TBI模型代表了用于开发CNS相关疾病的新治疗剂的合适模型。
Traumatic brain injury (TBI) is a major public and socioeconomic problem throughout the world. The establishment of an effective and cost-effective TBI model for developing new therapeutic agents is challenging. Microglia are considered the resident macrophages of the central nervous system (CNS) that normally do not enter the brain. As the primary mediators of the innate immune response in the CNS, microglia play a critical role in neuroinflammation and secondary injury after TBI. In this study, we established an in vivo TBI zebrafish model using Tg(coro1a:EGFP) line where the green fluorescent protein-labeled microglia were present. We demonstrated that microglia accumulated rapidly in response to neuronal injuries. To clear away injured neurons and restore the CNS homeostasis, activated microglia secreted two types of functional cytokines, including pro-inflammatory interleukins (IL) of IL-1 beta and IL-6 and anti-inflammatory factors of IL-4 and IL-10 in the lesioned larvae. Cytidine 5 '-Diphosphocholine (CDP-choline), as an effective and clinical neuroprotective drug, could further activate microglia, expressing high levels of il-1 beta, il-6, il-4, and il-10 in the TBI model. Moreover, CDP-choline reduced neuronal apoptosis and promoted neuronal proliferation around the lesioned site. Based on these results, the TBI model established in this study represents a suitable model for developing new therapeutic agents for CNS-associated diseases.