Gonzalez Rafael, Hickey Michelle J, Espinosa Julio M, Nistor Gabriel, Lane Thomas E, Keirstead Hans S
University of California, Reeve Irvine Research Center, Department of Anatomy and Neurobiology, 2111 Gillespie Neuroscience Research Facility, College of Medicine, Irvine, CA 92697-4292, USA.
Regen Med. 2007 Sep;2(5):771-83. doi: 10.2217/17460751.2.5.771.
Inflammation plays a critical role in the secondary degenerative response to spinal cord injury (SCI). The influx of inflammatory cells following SCI is preceded by the expression of specific chemoattractants, including chemokines. The chemokine CXCL10 is a potent T lymphocyte recruiter and has been strongly implicated in the pathology of many CNS disorders. We have previously demonstrated that CXCL10 exacerbates secondary degeneration by blocking the function of CXCL10 prior to SCI. Here we administered neutralizing antibodies against CXCL10 1 h after SCI in order to investigate the efficacy of this therapeutic intervention in abating histologic and functional deficit following acute SCI and further assess the functional role of CXCL10 in secondary degeneration. Neutralization of CXCL10 significantly reduced inflammation, apoptosis, neuronal loss and whole tissue loss. Notably, this therapeutic treatment also promoted revascularization of the injured spinal cord and functional recovery. These data suggest that anti-CXCL10 antibody treatment is a viable therapeutic strategy for acute SCI.
炎症在脊髓损伤（SCI）后的继发性退行性反应中起关键作用。SCI后炎症细胞的流入之前会有特定趋化因子的表达，包括趋化因子。趋化因子CXCL10是一种有效的T淋巴细胞募集剂，并且与许多中枢神经系统疾病的病理学密切相关。我们之前已经证明，在SCI之前阻断CXCL10的功能会加剧继发性退变。在此，我们在SCI后1小时给予抗CXCL10中和抗体，以研究这种治疗干预在减轻急性SCI后的组织学和功能缺陷方面的疗效，并进一步评估CXCL10在继发性退变中的功能作用。CXCL10的中和显著减少了炎症、细胞凋亡、神经元丢失和整个组织的丢失。值得注意的是，这种治疗方法还促进了损伤脊髓的血管再生和功能恢复。这些数据表明，抗CXCL10抗体治疗是急性SCI的一种可行治疗策略。
