一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Neural Regeneration Research >>article
Neural Regeneration Research

Neural Regeneration Research

IF: 5.9
Download PDF

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

Published:1 September 2025 DOI: 10.4103/NRR.NRR-D-23-01772 PMID: 39314167
Mengshi Yang,?Miao Bai,?Yuan Zhuang,?Shenghua Lu,?Qianqian Ge,?Hao Li,?Yu Deng,?Hongbin Wu,?Xiaojian Xu,?Fei Niu,?Xinlong Dong,?Bin Zhang,?Baiyun Liu

Abstract

JOURNAL/nrgr/04.03/01300535-202509000-00023/figure1/v/2024-11-05T132919Z/r/image-tiff Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury, the fundamental regulatory and functional mechanisms remain insufficiently understood. As potent anti-inflammatory agents, the use of glucocorticoids in traumatic brain injury is still controversial, and their regulatory effects on microglial polarization are not yet known. In the present study, we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action. In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization. Lipopolysaccharide, dexamethasone, RU486 (a glucocorticoid receptor antagonist), and ruxolitinib (a Janus kinase 1 antagonist) were administered. RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone. The Morris water maze, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence and confocal microscopy analysis, and TUNEL, Nissl, and Golgi staining were performed to investigate our hypothesis. High-throughput sequencing results showed that arginase 1, a marker of M2 microglia, was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at 3 days post-traumatic brain injury. Thus dexamethasone inhibited M1 and M2 microglia, with a more pronounced inhibitory effect on M2 microglia in vitro and in vivo . Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury. Additionally, glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death, and also decreased the density of dendritic spines. A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway. Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia, which plays an anti-inflammatory role. In contrast, inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury. Dexamethasone may exert its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ruxolitinib phosphate 1092939-17-7 C17H21N6O4P 388 suppliers $15.00-$3546.00
Ruxolitinib phosphate 1092939-17-7 C17H21N6O4P 388 suppliers $15.00-$3546.00
Ruxolitinib phosphate 1092939-17-7 C17H21N6O4P 388 suppliers $15.00-$3546.00
Ruxolitinib phosphate 1092939-17-7 C17H21N6O4P 388 suppliers $15.00-$3546.00

Similar articles

IF:5.3

Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Ling Ling, Min Luo,etc Published: 25 November 2024
IF:96.2

Placebo-controlled trial of amantadine for severe traumatic brain injury.

New England Journal of Medicine Joseph T Giacino, John Whyte,etc Published: 1 March 2012
IF:2.6

Sphingosine-1-phosphate receptor 3 promotes neuronal apoptosis via the TNF-α/caspase-3 signaling pathway after acute intracerebral hemorrhage

Molecular and Cellular Neuroscience Dengpan Song, Mengyuan Li,etc Published: 22 November 2024
北宁市| 吐鲁番市| 行唐县| 大同县| 盐亭县| 古蔺县| 灵台县| 闽清县| 永清县| 宁南县| 哈尔滨市| 甘南县| 武城县| 工布江达县| 东安县| 育儿| 北川| 黄骅市| 扎鲁特旗| 太仓市| 河池市| 柳林县| 保靖县| 潜江市| 奉贤区| 古蔺县| 碌曲县| 余干县| 泊头市| 博野县| 通州区| 安远县| 桃源县| 凤山县| 宜宾市| 甘德县| 墨竹工卡县| 德阳市| 江北区| 梅州市| 柳江县|