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血管病理学作为 SCI 的潜在治疗靶点。

Vascular Pathology as a Potential Therapeutic Target in SCI.

机构信息

Kentucky Spinal Cord Injury Research Center, 511 South Floyd Street, MDR Building, Room 616, Louisville, KY, 40292, USA,

出版信息

Transl Stroke Res. 2011 Dec;2(4):556-74. doi: 10.1007/s12975-011-0128-7. Epub 2011 Nov 29.

Abstract

Acute traumatic spinal cord injury (SCI) is characterized by a progressive secondary degeneration which exacerbates the loss of penumbral tissue and neurological function. Here, we first provide an overview of the known pathophysiological mechanisms involving injured microvasculature and molecular regulators that contribute to the loss and dysfunction of existing and new blood vessels. We also highlight the differences between traumatic and ischemic injuries which may yield clues as to the more devastating nature of traumatic injuries, possibly involving toxicity associated with hemorrhage. We also discuss known species differences with implications for choosing models, their relevance and utility to translate new treatments towards the clinic. Throughout this review, we highlight the potential opportunities and proof-of-concept experimental studies for targeting therapies to endothelial cell-specific responses. Lastly, we comment on the need for vascular mechanisms to be included in drug development and non-invasive diagnostics such as serum and cerebrospinal fluid biomarkers and imaging of spinal cord pathology.

摘要

急性创伤性脊髓损伤(SCI)的特征是进行性继发性退化,这加剧了半影组织和神经功能的丧失。在这里,我们首先概述了已知的病理生理机制,包括涉及损伤微血管和分子调节剂的机制,这些机制导致现有和新血管的丧失和功能障碍。我们还强调了创伤性和缺血性损伤之间的差异,这可能为创伤性损伤更具破坏性的性质提供线索,可能涉及与出血相关的毒性。我们还讨论了已知的物种差异,这些差异可能对选择模型具有重要意义,对将新的治疗方法转化为临床应用具有相关性和实用性。在整篇综述中,我们强调了针对内皮细胞特异性反应的靶向治疗的潜在机会和概念验证实验研究。最后,我们评论了将血管机制纳入药物开发和非侵入性诊断(如血清和脑脊液生物标志物以及脊髓病理成像)的必要性。

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