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Olfactory Ensheathing Cell Ameliorate Neuroinflammation Following Spinal Cord Injury Through Upregulating REV-ERBα in Microglia

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机构: [1]Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China. [2]Postdoctoral Research Station of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China. [3]Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China. [4]Clinical Medicine College, Affiliated Hospital of Hebei University, Hebei University, Baoding, China. [5]Department of Pathology, Affiliated Hospital of Hebei University, Baoding, China.
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关键词: olfactory ensheathing cells spinal cord injury neuroinflammation circadian clock REV-ERBα

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Circadian dysregulation involved in the pathophysiology of spinal cord injury (SCI). Modulation of circadian rhythms hold promise for the SCI treatment. Here, we aim to investigated the mechanism of olfactory ensheathing cells (OEC) in alleviating neuroinflammation via modulating clock gene expression in microglia. In this study, SCI rats were randomly divided into OEC group and vehicle group. At 1 day after the surgery, OECs were intravenously transplanted into OEC group SCI rat, while the rats in vehicle group received culture medium. After 7 days post of OEC transplantation, tissues were collected from the brain (prefrontal cortex, hypothalamus, spinal cord) for PCR, western blotting and immunohistochemistry (IHC) assay at zeitgeber time (ZT) 6, ZT 12, ZT 18, and ZT 24. The roles of OEC in modulating REV-ERBα in microglia were studied by experimental inhibition of gene expression and the co-culture experiment. In the vehicle group, IHC showed a significant increase of Iba-1 expression in the cerebral white matter and spinal cord compared with control group (P < 0.0001 for all comparisons). The expression of Iba-1 was significantly decreased (P < 0.0001 for all comparisons). In the OEC group, the expression of PER 1, PER 2, CLOCK, and REV-ERBα was in a rhythmical manner in both spinal cord and brain regions. SCI disrupted their typical rhythms. And OECs transplantation could modulate those dysregulations by upregulating REV-ERBα. In vitro study showed that OECs couldn't reduce the activation of REV-ERBα inhibited microglia. The intravenous transplantation of OECs can mediate cerebral and spinal microglia activation through upregulation REV-ERBα after SCI.

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大类 | 4 区 医学
小类 | 3 区 移植 4 区 细胞与组织工程 4 区 医学:研究与实验
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出版当年[2024]版:
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Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 TRANSPLANTATION Q3 CELL & TISSUE ENGINEERING

影响因子: 最新[2023版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2023版]

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第一作者机构: [1]Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China. [2]Postdoctoral Research Station of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China. [3]Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China.
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通讯机构: [1]Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China. [2]Postdoctoral Research Station of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China. [3]Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China.
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