Application of the Zebrafish Traumatic Brain Injury Model in Assessing Cerebral Inflammation

Daqing Gan, Shuilong Wu, Bing Chen, Jingjing Zhang
Zebrafish 2020, 17 (2): 73-82
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 β 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 β, 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.

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