Traumatic Spinal Cord Injury-Repair and Regeneration
Traumatic Spinal Cord Injury-Repair and Regeneration
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DOI：
10.1093/neuros/nyw080
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发表时间：
2017-03-01
期刊：
影响因子：
4.8
通讯作者：
Fehlings, Michael G.
中科院分区：
文献类型：
--
作者：
Ahuja, Christopher S.;Nori, Satoshi;Fehlings, Michael G.
背景技术背景：创伤性脊髓损伤（SCI）对患者及其护理人员的身体，经济和心理健康具有毁灭性的后果。在早期postinjury期间迅速提供干预措施可以有一个巨大的影响长期的功能recovery.Pathophysiology.This是由于SCI的初始创伤性损伤（原发性损伤）的独特的病理生理学，其次是一个渐进的继发性损伤级联缺血，促凋亡信号，和外周炎性细胞浸润的特点。在随后的几个小时内，促炎细胞因子和细胞毒性碎片（DNA，ATP，活性氧）的释放周期性地增加了苛刻的损伤后微环境。随着病变发展到慢性期，合并囊腔周围的星形胶质细胞纤维瘢痕的形成严重阻碍了再生。应对这些挑战形成了当前和即将到来的治疗SCI.MANAGEMENT的基础：本文讨论了SCI患者的循证管理，同时强调早期明确护理的重要性。总结了关键的神经保护治疗，包括手术减压，甲泼尼龙，和血压升高。然后，我们回顾了令人兴奋的神经保护干预的尖端翻译，如阿曲唑，米诺环素，镁，治疗性低温，脑脊液引流。我们还探索了目前最有前途的神经再生策略，包括Cethrin（TM），抗NOGO抗体，基于细胞的方法和生物工程生物材料。每一节提供了一个工作知识的关键临床前和患者试验相关的临床医生，同时突出的病理生理学原理的therapeutis.CONCLUSION：我们的结论与我们的观点在这个迅速发展的领域的治疗和研究的未来。
BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery.PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration. Over the subsequent hours, release of proinflammatory cytokines and cytotoxic debris (DNA, ATP, reactive oxygen species) cyclically adds to the harsh postinjury microenvironment. As the lesions mature into the chronic phase, regeneration is severely impeded by the development of an astroglial-fibrous scar surrounding coalesced cystic cavities. Addressing these challenges forms the basis of current and upcoming treatments for SCI.MANAGEMENT: This paper discusses the evidence-based management of a patient with SCI while emphasizing the importance of early definitive care. Key neuroprotective therapies are summarized including surgical decompression, methylprednisolone, and blood pressure augmentation. We then review exciting neuroprotective interventions on the cusp of translation such as Riluzole, Minocycline, magnesium, therapeutic hypothermia, and CSF drainage. We also explore the most promising neuroregenerative strategies in trial today including Cethrin (TM), anti-NOGO antibody, cell-based approaches, and bioengineered biomaterials. Each section provides a working knowledge of the key preclinical and patient trials relevant to clinicians while highlighting the pathophysiologic rationale for the therapies.CONCLUSION: We conclude with our perspectives on the future of treatment and research in this rapidly evolving field.