Zhou, ChangweiSun, RongSun, ChongyiGu, MinghaoGuo, ChuanZhang, JiyanDu, YanshengGu, HuiyingLiu, Qingpeng2021-03-302021-03-302020-01-01Zhou, C., Sun, R., Sun, C., Gu, M., Guo, C., Zhang, J., Du, Y., Gu, H., & Liu, Q. (2020). Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity. Brain Research Bulletin, 154, 102–105. https://doi.org/10.1016/j.brainresbull.2019.11.0050361-9230https://hdl.handle.net/1805/25508Unconjugated bilirubin, the end product of heme catabolism and antioxidant, induced brain damage in human neonates is a well-recognized clinical syndrome. However, the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain unclear. To characterize the sequence of events leading to bilirubin-induced neurotoxicity, we investigated whether bilirubin-induced glial activation was involved in bilirubin neurotoxicity by exposing co-cultured rat glial cells and cerebellar granule neurons (CGN) to bilirubin. We found that bilirubin could markedly induce the expression of TNF-α and iNOS in glial cells, and even at low concentrations, the co-culture of glial cells with neurons significantly enhances neurotoxicity of bilirubin. Pretreatment of the co-cultured cells with minocycline protected CGN from glia-mediated bilirubin neurotoxicity and inhibited overexpression of TNF-α and iNOS in glia. Furthermore, we found that high doses of bilirubin were able to induce glial injury, and minocycline attenuated bilirubin-induced glial cell death. Our data suggest that glial cells play an important role in brain damage caused by bilirubin, and minocycline blocks bilirubin-induced encephalopathy possibly by directly and indirectly inhibiting neuronal death pathways.en-USMinocyclineBilirubinGliaNeurotoxicityNeuroprotectionArticle