Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation.
Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation.
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DOI：
10.1016/j.expneurol.2012.02.016
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发表时间：
2012-05
影响因子：
5.3
通讯作者：
Flanagan, Lisa A.
中科院分区：
文献类型：
--
作者：
Sharp, Kelli G.;Dickson, Amanda R.;Marchenko, Steve A.;Yee, Kelly M.;Emery, Pauline N.;Laidmae, Ivo;Uibo, Raivo;Sawyer, Evelyn S.;Steward, Oswald;Flanagan, Lisa A.
脊髓损伤引起的神经变性在损伤部位留下一个空洞，极大地抑制了修复。促进修复的一种方法是用支架填充空洞，以限制进一步的损伤并鼓励再生。可注射材料是有利的支架，因为它们可以作为液体放置在病变部位，然后在体内形成与病变轮廓精确匹配的固体。纤维蛋白是一种可注射的支架，但血液传播病原体感染的风险限制了它的使用。我们研究了鲑鱼纤维蛋白作为可注射支架治疗脊髓损伤的潜在效用，因为它没有哺乳动物感染因子，并且在体外比哺乳动物纤维蛋白或另一种可注射材料Matrigel®更能促进神经元伸展。雌性大鼠接受T9背侧半横断损伤，并在受伤时接受鲑鱼或人纤维蛋白治疗，而第三组作为未处理的对照组。运动功能采用BBB评分，膀胱功能采用残余尿量测定，感觉反应采用机械刺激(Von Frey Hair)。组织学分析量化了胶质瘢痕、病变体积和5-羟色胺能纤维密度。服用鲑鱼纤维蛋白的大鼠运动和膀胱功能的恢复都有显著改善，病变部位尾部的5-羟色胺能神经支配密度更高，而不会加剧疼痛。用鲑鱼纤维蛋白治疗的大鼠比用人纤维蛋白治疗的大鼠表现出更少的自噬，这可能表明感觉功能障碍的改善。胶质瘢痕的形成和病变大小在不同组之间没有显著差异。鲑鱼纤维蛋白作用的模式和时间表明，它作用于神经元群体，而不是通过刺激长管再生。鲑鱼纤维蛋白显然具有与哺乳动物纤维蛋白不同的特性，是治疗脊髓损伤的一种有益的可注射支架。
The neural degeneration caused by spinal cord injury leaves a cavity at the injury site that greatly inhibits repair. One approach to promoting repair is to fill the cavity with a scaffold to limit further damage and encourage regrowth. Injectable materials are advantageous scaffolds because they can be placed as a liquid in the lesion site then form a solid in vivo that precisely matches the contours of the lesion. Fibrin is one type of injectable scaffold, but risk of infection from blood borne pathogens has limited its use. We investigated the potential utility of salmon fibrin as an injectable scaffold to treat spinal cord injury since it lacks mammalian infectious agents and encourages greater neuronal extension in vitro than mammalian fibrin or Matrigel®, another injectable material. Female rats received a T9 dorsal hemisection injury and were treated with either salmon or human fibrin at the time of injury while a third group served as untreated controls. Locomotor function was assessed using the BBB scale, bladder function was analyzed by measuring residual urine, and sensory responses were tested by mechanical stimulation (von Frey hairs). Histological analyses quantified the glial scar, lesion volume, and serotonergic fiber density. Rats that received salmon fibrin exhibited significantly improved recovery of both locomotor and bladder function and a greater density of serotonergic innervation caudal to the lesion site without exacerbation of pain. Rats treated with salmon fibrin also exhibited less autophagia than those treated with human fibrin, potentially pointing to amelioration of sensory dysfunction. Glial scar formation and lesion size did not differ significantly among groups. The pattern and timing of salmon fibrin’s effects suggest that it acts on neuronal populations but not by stimulating long tract regeneration. Salmon fibrin clearly has properties distinct from those of mammalian fibrin and is a beneficial injectable scaffold for treatment of spinal cord injury.
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