Microglial Priming in Bilirubin-Induced Neurotoxicity

作者全名："Huang, Hongmei; Li, Siyu; Zhang, Yan; He, Chunmei; Hua, Ziyu"

作者地址："[Huang, Hongmei; Li, Siyu; He, Chunmei; Hua, Ziyu] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Childrens Hosp, Dept Neonatol,Minist Educ,Key Lab Child Dev & Diso, Chongqing, Peoples R China; [Huang, Hongmei; Li, Siyu; Zhang, Yan; He, Chunmei; Hua, Ziyu] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Huang, Hongmei; Li, Siyu; Zhang, Yan; He, Chunmei; Hua, Ziyu] Chongqing Key Lab Child Infect & Immun, Chongqing, Peoples R China"

通信作者："Hua, ZY (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Childrens Hosp, Dept Neonatol,Minist Educ,Key Lab Child Dev & Diso, Chongqing, Peoples R China.; Hua, ZY (通讯作者)，China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China.; Hua, ZY (通讯作者)，Chongqing Key Lab Child Infect & Immun, Chongqing, Peoples R China."

来源：NEUROTOXICITY RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000968058700001

JCR分区：Q2

影响因子：2.9

年份：2023

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文献类型：Article; Early Access

关键词：Bilirubin; Microglia; Neuron; Inflammation; Neurotoxicity; VX-765

摘要："Neuroinflammation is a major contributor to bilirubin-induced neurotoxicity, which results in severe neurological deficits. Microglia are the primary immune cells in the brain, with M1 microglia promoting inflammatory injury and M2 microglia inhibiting neuroinflammation. Controlling microglial inflammation could be a promising therapeutic strategy for reducing bilirubin-induced neurotoxicity. Primary microglial cultures were prepared from 1-3-day-old rats. In the early stages of bilirubin treatment, pro-/anti-inflammatory (M1/M2) microglia mixed polarization was observed. In the late stages, bilirubin persistence induced dominant proinflammatory microglia, forming an inflammatory microenvironment and inducing iNOS expression as well as the release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta. Simultaneously, nuclear factor-kappa B (NF-kappa B) was activated and translocated into the nucleus, upregulating inflammatory target genes. As well known, neuroinflammation can have an effect on N-methyl-D-aspartate receptor (NMDAR) expression or function, which is linked to cognition. Treatment with bilirubin-treated microglia-conditioned medium did affect the expression of IL-1 beta, NMDA receptor subunit 2A (NR2A), and NMDA receptor subunit 2B (NR2B) in neurons. However, VX-765 effectively reduces the levels of proinflammatory cytokines TNF-alpha, IL-6, and IL-1 beta, as well as the expressions of CD86, and increases the expressions of anti-inflammatory related Arg-1. A timely reduction in proinflammatory microglia could protect against bilirubin-induced neurotoxicity."

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