Enhanced Repair Effect of Toll-Like Receptor 4 Activation on Neurotmesis: Assessment Using MR Neurography

Enhanced Repair Effect of Toll-Like Receptor 4 Activation on Neurotmesis: Assessment Using MR Neurography
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Toll 样受体 4 激活对神经断裂的增强修复作用:使用 MR 神经造影进行评估

DOI:
10.3174/ajnr.a3977
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发表时间:
2014-08-01
影响因子:
3.5
通讯作者:
Shen, J.
Shen, J.
中科院分区:
医学2区
文献类型:
--
作者:
Li, H. J.;Zhang, X.;Shen, J.

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背景和目的:在神经断伤的外科修复中,替代使用分子方法有望改善神经再生。本研究的目的是确定MR成像在评估Toll样受体4信号激活在神经断伤手术修复中促进神经再生中的作用。材料和方法:48只健康大鼠,其中坐骨神经被手术切断,然后立即手术接合,接受腹腔内注射toll样受体4激动剂脂多糖(n = 24,研究组)或磷酸盐缓冲盐水(n = 24,对照组),直到术后第7天。在8周的随访期内,连续进行T2测量和钆氟M增强MR成像以及坐骨神经功能指数,并定期进行组织学评估。T2弛豫时间和gadofluorine增强的远端神经残端进行了测量和比较脂多糖和磷酸盐缓冲盐水处理的神经。研究结果:与磷酸盐缓冲盐水处理的神经相比,脂多糖注射处理的神经实现了更好的功能恢复,并且在退行性阶段显示出更突出的钆氟增强和延长的T2值。脂多糖治疗的神经T2值比钆氟增强更快地恢复到基线水平。组织学表现出更多的巨噬细胞募集,更快的髓鞘碎片清除,和更明显的神经再生与toll样受体4激活治疗的神经。结论:Toll样受体4激活在神经断伤手术修复中的增强神经修复可以通过使用钆氟M增强MR成像和T2弛豫时间测量来监测。T2弛豫时间似乎比钆氟M增强MR成像更敏感,用于检测这种改善的神经再生。
BACKGROUND AND PURPOSE: Alternative use of molecular approaches is promising for improving nerve regeneration in surgical repair of neurotmesis. The purpose of this study was to determine the role of MR imaging in assessment of the enhanced nerve regeneration with toll-like receptor 4 signaling activation in surgical repair of neurotmesis. MATERIALS AND METHODS: Forty-eight healthy rats in which the sciatic nerve was surgically transected followed by immediate surgical coaptation received intraperitoneal injection of toll-like receptor 4 agonist lipopolysaccharide (n = 24, study group) or phosphate buffered saline (n = 24, control group) until postoperative day 7. Sequential T2 measurements and gadofluorine M-enhanced MR imaging and sciatic functional index were obtained over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and gadofluorine enhancement of the distal nerve stumps were measured and compared between nerves treated with lipopolysaccharide and those treated with phosphate buffered saline. RESULTS: Nerves treated with lipopolysaccharide injection achieved better functional recovery and showed more prominent gadofluorine enhancement and prolonged T2 values during the degenerative phase compared with nerves treated with phosphate buffered saline. T2 values in nerves treated with lipopolysaccharide showed a more rapid return to baseline level than did gadofluorine enhancement. Histology exhibited more macrophage recruitment, faster myelin debris clearance, and more pronounced nerve regeneration in nerves treated with toll-like receptor 4 activation. CONCLUSIONS: The enhanced nerve repair with toll-like receptor 4 activation in surgical repair of neurotmesis can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting such improved nerve regeneration.