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.
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