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Glial scarring limits recovery following decompressive surgery in rats with syringomyelia

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机构: [1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China [2]Spine Center, China International Neuroscience Institute (CHINA-INI), Beijing, China [3]Research Center of Spine and Spinal Cord, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China [4]Lab of Spinal Cord Injury and Functional Reconstruction, China International Neuroscience Institute (CHINA-INI), Xuanwu Hospital, Capital Medical University, Beijing, China [5]Department of Neurosurgery, The First Hospital of Hebei Medical University, Shijiazhuang, China [6]Baylor College of Medicine, Houston, TX, USA [7]Department of Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China [8]Capital Medical University, Beijing, China
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关键词: Syringomyelia Glial scar Subarachnoid space Syrinx Fluorocitrate Decompression surgery

摘要:
Syringomyelia is a neurological disease that is difficult to cure, and treatments often have limited effectiveness. In this study, a rat model of syringomyelia induced by epidural compression was used to investigate the factors that limit the prognosis of syringomyelia. After we treated syringomyelia rats with surgical decompression alone, MRI revealed that the syringomyelia rats did not show the expected therapeutic effect. Through cerebrospinal fluid (CSF) tracing experiments, we found that the CSF flow in the subarachnoid space (SAS) of rats was restored after decompression. This shows that the poor prognosis of syringomyelia rats in this study is not caused by CSF circulation disorders, suggesting the existence of other factors. Further, immunofluorescence revealed that there were extensive glial scars characterized by increased expression of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) around the syrinx in the non-improved group compared to the improved group. To verify the limiting role of glial scarring in the prognosis of syringomyelia, we intervened with the selective astrocyte inhibitor fluorocitrate (FC). Intrathecal injection of FC significantly inhibited the formation of glial scar after decompression in syringomyelia rats and promoted the reduction of syrinx. This scar-inhibiting effect significantly improved neuronal survival, promoted axonal and myelin recovery, and showed better recovery in sensory function and fine motor control functions. These findings suggest that glial scarring around syrinx is a key factor limiting recovery of syringomyelia. By inhibiting glial scar formation, the prognosis of syringomyelia can be significantly improved, which provides a new strategy for improving clinical treatment effects.Copyright © 2024. Published by Elsevier Inc.

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 2 区 神经科学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 神经科学
第一作者:
第一作者机构: [1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China [2]Spine Center, China International Neuroscience Institute (CHINA-INI), Beijing, China [3]Research Center of Spine and Spinal Cord, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China [4]Lab of Spinal Cord Injury and Functional Reconstruction, China International Neuroscience Institute (CHINA-INI), Xuanwu Hospital, Capital Medical University, Beijing, China
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通讯机构: [1]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China [2]Spine Center, China International Neuroscience Institute (CHINA-INI), Beijing, China [3]Research Center of Spine and Spinal Cord, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China [4]Lab of Spinal Cord Injury and Functional Reconstruction, China International Neuroscience Institute (CHINA-INI), Xuanwu Hospital, Capital Medical University, Beijing, China
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