sco - spondnin衍生肽NX210促进小鼠脊髓损伤后功能恢复。

IF 3.8 2区 医学 Q1 CLINICAL NEUROLOGY
Theresa C Sutherland, Sighild Lemarchant, Ashley J Douthitt, Alexandra H Lopez, Lily Kuhlman, Darijana Horvat, Arthur Sefiani, Sydney M Johnson, Zoha Hassan, Natalie Bachir, Ravali Dundumulla, Michelle Hook, Yann Godfrin, Cédric G Geoffroy
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引用次数: 0

摘要

脊髓损伤(SCI)是一个重大的公共卫生问题,因为其后果往往是不可逆转的,目前尚无治疗方法。这导致越来越多的人生活在与脊髓损伤直接相关的长期运动、感觉和/或自主神经损伤中。在这里,我们评估了一种名为NX210的血栓反应蛋白重复肽类似物在脊髓损伤小鼠半切模型中的治疗潜力。成年雌性小鼠接受胸部8级背侧半切,并在损伤后4小时开始腹腔注射NX210,然后每周两次以4、8或16 mg/kg的剂量注射。使用Basso小鼠评分(BMS)评分和亚评分、旋转杆和活动室测试,每周评估一次后肢运动功能,持续10周。然后处死小鼠,收集脊髓进行免疫组化。有趣的是,NX210改善了功能恢复(BMS评分和亚评分,从旋转杆下降的潜伏期,自发运动活动),功能快速上升,并在整个10周的研究中保持。这伴随着通过甩尾测试评估的伤害性反应的减少。NX210治疗也增加了损伤部位10周后的髓鞘碱性蛋白,减少了神经元/胶质抗原2,但对病变大小、炎症和神经元存活没有显著影响。总的来说,这项研究强调了一种潜在的新的治疗策略,可以促进脊髓损伤后的修复和减少长期的功能损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SCO-Spondin-Derived Peptide NX210 Promotes Functional Recovery after Spinal Cord Injury in Mice.

Spinal cord injury (SCI) represents a major public health issue, as the consequences are often irreversible with no treatment currently available. This results in a growing population living with long-lasting motor, sensory, and/or autonomic impairments directly related to their SCI. Here, we have evaluated the therapeutic potential of a thrombospondin repeats peptide analogue, named NX210, in a mouse hemisection model of SCI. Adult female mice were subjected to a thoracic level 8 dorsal hemisection, and treated with intraperitoneal injections of NX210 starting at 4 h post-injury and then twice a week at 4, 8, or 16 mg/kg. Hind limb motor function was assessed once a week for 10 weeks post-injury using the Basso Mouse Scale (BMS) score and sub-score, the rotarod, and the activity chamber tests. Mice were then sacrificed, and the spinal cords were collected for immunohistochemistry. Interestingly, NX210 improved functional recovery (BMS score and sub-score, latency to fall from the rotarod, spontaneous locomotor activity) with rapid rises in function that were maintained throughout the 10-week study. This was accompanied by a reduction of nociceptive reactivity assessed by the tail flick test. NX210 treatment also increased myelin basic protein and reduced neuron/glial antigen 2 at the injury site 10 weeks post-injury while no significant effects were observed on lesion size, inflammation, and neuron survival. Overall, this study highlights a potential new therapeutic strategy to promote repair and decrease long-lasting functional impairments after SCI.

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来源期刊
Journal of neurotrauma
Journal of neurotrauma 医学-临床神经学
CiteScore
9.20
自引率
7.10%
发文量
233
审稿时长
3 months
期刊介绍: Journal of Neurotrauma is the flagship, peer-reviewed publication for reporting on the latest advances in both the clinical and laboratory investigation of traumatic brain and spinal cord injury. The Journal focuses on the basic pathobiology of injury to the central nervous system, while considering preclinical and clinical trials targeted at improving both the early management and long-term care and recovery of traumatically injured patients. This is the essential journal publishing cutting-edge basic and translational research in traumatically injured human and animal studies, with emphasis on neurodegenerative disease research linked to CNS trauma.
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