Artemin induced functional recovery and reinnervation after partial nerve injury.

Artemin induced functional recovery and reinnervation after partial nerve injury.
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DOI:
10.1016/j.pain.2013.11.007
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发表时间:
2014-03
期刊:
影响因子:
7.4
通讯作者:
Porreca F
Porreca F
中科院分区:
医学1区
文献类型:
--
作者:
Wang R;Rossomando A;Sah DWY;Ossipov MH;King T;Porreca F

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全身青蒿素促进挤压伤后背根到脊髓的再生。然而,目前尚不清楚全身青蒿素是否能促进背根节(DRG)远端周围神经的再生和功能恢复。在本研究中,雄性SD大鼠接受了L5脊神经切断、结扎或挤压或假手术。从受伤当天开始,动物接受间歇性皮下注射。青蒿素或车辆跨越2周。伤后6周监测对触觉或热刺激的感觉阈值。6周时行背根神经节和神经再生的免疫组织化学分析。青蒿素可短暂逆转轴突切断、结扎或挤压伤后的触觉和热过敏。治疗结束后1周内再次出现热敏和触觉过敏。然而,青蒿素治疗的大鼠只接受神经挤压,而不是切断或结扎神经,随后在损伤后6周,感觉阈值逐渐恢复到损伤前的基线水平。Artemin使挤压伤远端神经纤维中NF200、IB4和CGRP的标记正常化,表明神经挤压引起的神经化学变化持续正常化。挤压伤部位远端的坐骨神经和皮内注射葡聚糖或CTB可标记L5背根节的神经元轮廓,提示穿过损伤部位的无髓纤维和有髓纤维功能恢复到皮肤组织中。青蒿素还降低L5背根节ATF3和caspase-3的表达,提示持续的神经保护作用。有限的青蒿素治疗通过促进远端区域的感觉神经再支配和恢复受伤前的感觉阈值来引起疾病的改变。
Systemic artemin promotes regeneration of dorsal roots to the spinal cord following crush injury. However, it is unclear whether systemic artemin can promote peripheral nerve regeneration and functional recovery distal to the dorsal root ganglion (DRG). In the present investigation, male SD rats received axotomy, ligation, or crush of the L5 spinal nerve or sham surgery. Starting the day of injury, animals received intermittent s.c. artemin or vehicle across 2 weeks. Sensory thresholds to tactile or thermal stimuli were monitored for 6 weeks following injury. Immunohistochemical analyses of the DRG and nerve regeneration were performed at the 6 week timepoint. Artemin transiently reversed tactile and thermal hypersensitivity following axotomy, ligation or crush injury. Thermal and tactile hypersensitivity re-emerged within 1 week of treatment termination. However, artemin treated rats with nerve crush, but not axotomy or ligation, subsequently showed gradual return of sensory thresholds to pre-injury baseline levels by 6 weeks post-injury. Artemin normalized labeling for NF200, IB4 and CGRP in nerve fibers distal to the crush injury, suggesting persistent normalization of nerve-crush induced neurochemical changes. Sciatic and intradermal administration of dextran or CTB distal to the crush injury site resulted in labeling of neuronal profiles in the L5 DRG, suggesting functional restoration of non-myelinated and myelinated fibers across the injury site into cutaneous tissue. Artemin also diminished ATF3 and caspase-3 expression in the L5 DRG, suggesting persistent neuroprotective actions. A limited period of artemin treatment elicits disease modification by promoting sensory reinnervation of distal territories and restoring pre-injury sensory thresholds.
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