中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (6): 1060-1068.doi: 10.4103/1673-5374.250627

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

多种方法联合治疗方案对促进急性脊髓损伤后神经保护和再生有较好的效果

  

  • 出版日期:2019-06-15 发布日期:2019-06-15
  • 基金资助:

    墨西哥国家科学技术委员会（CONACYT）支持

Use of a combination strategy to improve neuroprotection and neuroregeneration in a rat model of acute spinal cord injury

Elisa García 1, 2 , Roxana Rodríguez-Barrera 1, 2 , Vinnitsa Buzoianu-Anguiano 3 , Adrian Flores-Romero 1, 2 , Emanuel Malagón-Axotla 1 , Marco Guerrero-Godinez 4 , Estefanía De la Cruz-Castillo 1 , Laura Castillo-Carvajal 1 , Monserrat Rivas-Gonzalez 1 , Paola Santiago-Tovar 1 , Ivis Morales 1 , Cesar Borlongan 5 , Antonio Ibarra 1, 2   

  1. 1 Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Edo. de México, México
    2 Centro de Investigación del Proyecto CAMINA A.C.; Ciudad de México, México
    3 Unidad de Investigación Médica en Enfermedades Neurologicas, Hospital Especialidades CMN Siglo XXI, Ciudad de México, Mexico
    4 Unidad de Rehabilitación Osteoarticular. Instituto Nacional de Rehabilitación. Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico
    5 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA
  • Online:2019-06-15 Published:2019-06-15
  • Contact: Antonio Ibarra, MD, MSc, DrSc, jose.ibarra@anahuac.mx.
  • Supported by:

    This work was supported by the National Council of Science and Technology of Mexico (CONACYT), No. 178544 (to AI).

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摘要：

研究者们正在探索几种策略共同应用来促进脊髓损伤后的神经保护或神经再生，但如何获得最佳效果尚有待进一步研究。实验旨在评估用神经衍生肽免疫，抑制胶质瘢痕形成的联吡啶，以及浸润有骨髓间充质干细胞的生物相容性基质纤维蛋白胶联合干预对急性脊髓损伤后的神经保护和神经再生诱导作用。选择SD雌性成年大鼠以重物自由坠落的方法建立中度脊髓损伤模型后72h，随机分给予如下5种干预：（1）磷酸盐缓冲液; （2）联吡啶; （3）神经衍生肽 +联吡啶;（ 4）联吡啶 +纤维蛋白胶; （5）联合治疗组为神经衍生肽 +联吡啶 +纤维蛋白胶 + 骨髓间充质干细胞。BBB评分和Von Frey测痛仪评估结果显示，神经衍生肽 +联吡啶 +纤维蛋白胶 + 骨髓间充质干细胞联合治疗方案促进脊髓损伤大鼠运动和感觉功能恢复的效果最佳；苏木素-伊红和Bielschowsky染色结果显示，联合治疗方案对促进损伤脊髓组织保存和提高轴突密度方面作用最为显著；结果证实了联合治疗方案对急性脊髓损伤后神经组织的保护和再生的最佳阳性作用。

orcid: 0000-0003-2489-4689 (Antonio Ibarra)

关键词: 脊髓损伤, 纤维蛋白胶, 间充质干细胞, 胶质瘢痕, 保护性自身免疫, 神经衍生肽, 神经再生

Abstract:

Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides (INDP), inhibition of glial scar formation (dipyridyl: DPY), as well as the use of biocompatible matrix (fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells (MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord (hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy (DPY+ INDP + FG + MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy (DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee (aproval number: 178544; CSNBTBIBAJ 090812960) on August 15, 2016.

Key words: fibrin glue, mesenchymal stem cells, glial scar, protective autoimmunity, neural derived peptides, neural regeneration