Student Competition (Knowledge Generation) ID 1987548

IF 2.4 Q1 REHABILITATION
S. Brockie, C. Zhou, M. Movahed, J. Hong, M. G. Fehlings
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引用次数: 0

Abstract

Degenerative cervical myelopathy (DCM) is the most common form of spinal impairment worldwide and is caused by a series of degenerative changes that compress the spinal cord. DCM can be treated with surgical decompression (DEC), but recovery is impaired by secondary injury, such that 44% of patients who undergo DEC never regain lost function, and 9% experience persistent decline. The fractalkine receptor, CX3CR1, is expressed by monocyte-derived macrophages and CNS-resident microglia, where it mediates communication with neurons expressing its ligand, CX3CL1, and maintains phagocytic, migration, and injury response functions. The purpose of this study is to determine the role of fractalkine in degeneration and post-surgical injury. We hypothesize that CX3CR1 expression is elevated by DCM and DEC and that inhibiting it may attenuate inflammation and improve functional outcomes. To determine this, I am using a mouse model of C5-6 myelopathy in Cx3cr1-knockout and wildtype mice to produce functional degeneration and neuropathic pain across a 12-week period. Immunostaining of spinal tissue from myelo-pathic wildtype mice indicates upregulation of CX3CR1 throughout DCM and confirms this expression to be mediated by resident microglia. Inhibiting fractalkine signalling attenuates neuropathic pain across DCM progression. Following DEC, these benefits are reversed, and knockouts experience more pain up to 5 weeks post-surgery, suggesting a critical role for CX3CR1 in mediating secondary injury. My findings thus far indicate a significant role played by fractalkine signaling in DCM and DEC recovery and posit microglia as a target for therapeutic intervention.
学生竞赛(知识生成) ID 1987548
退行性颈椎脊髓病(DCM)是全球最常见的脊髓损伤形式,由一系列压迫脊髓的退行性病变引起。颈椎退行性病变可通过手术减压(DEC)治疗,但二次损伤会影响患者的康复,44%的患者在接受手术减压后再也无法恢复丧失的功能,9%的患者功能持续下降。单核细胞衍生的巨噬细胞和中枢神经系统驻留的小胶质细胞表达分叉碱受体 CX3CR1,它介导与表达其配体 CX3CL1 的神经元之间的交流,并维持吞噬、迁移和损伤反应功能。 本研究的目的是确定fractalkine在变性和手术后损伤中的作用。我们假设,CX3CR1 的表达会因 DCM 和 DEC 而升高,抑制它可能会减轻炎症反应并改善功能预后。 为了确定这一点,我正在使用 Cx3cr1 基因敲除小鼠和野生型小鼠的 C5-6 脊髓病变模型,以产生为期 12 周的功能退化和神经病理性疼痛。 对肌病野生型小鼠脊髓组织的免疫染色表明,CX3CR1在整个DCM中上调,并证实这种表达是由常驻小胶质细胞介导的。抑制 fractalkine 信号可减轻整个 DCM 进程中的神经性疼痛。在 DEC 之后,这些益处被逆转,基因敲除者在手术后 5 周内会经历更多疼痛,这表明 CX3CR1 在介导继发性损伤方面起着关键作用。 我迄今为止的研究结果表明,分叉蛋白信号在 DCM 和 DEC 恢复中发挥了重要作用,并认为小胶质细胞是治疗干预的目标。
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来源期刊
CiteScore
3.20
自引率
3.40%
发文量
33
期刊介绍: Now in our 22nd year as the leading interdisciplinary journal of SCI rehabilitation techniques and care. TSCIR is peer-reviewed, practical, and features one key topic per issue. Published topics include: mobility, sexuality, genitourinary, functional assessment, skin care, psychosocial, high tetraplegia, physical activity, pediatric, FES, sci/tbi, electronic medicine, orthotics, secondary conditions, research, aging, legal issues, women & sci, pain, environmental effects, life care planning
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