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创伤性脊髓损伤后血管破坏及血脊髓屏障通透性的特征分析

Characterization of vascular disruption and blood-spinal cord barrier permeability following traumatic spinal cord injury.

作者信息

Figley Sarah A, Khosravi Ramak, Legasto Jean M, Tseng Yun-Fan, Fehlings Michael G

机构信息

1 Department of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network , Toronto, Ontario, Canada .

出版信息

J Neurotrauma. 2014 Mar 15;31(6):541-52. doi: 10.1089/neu.2013.3034. Epub 2014 Jan 11.

Abstract

Significant vascular changes occur subsequent to spinal cord injury (SCI), which contribute to progressive pathophysiology. In the present study, we used female Wistar rats (300-350 g) and a 35-g clip-compression injury at T6 to T7 to characterize the spatial and temporal vascular changes that ensue post-SCI. Before sacrifice, animals were injected with vascular tracing dyes (2% Evans Blue (EB) or fluorescein isothiocyanate/Lycopersicon esculentum agglutinin [FITC-LEA]) to assess blood-spinal cord barrier (BSCB) integrity or vascular architecture, respectively. Spectrophotometry of EB tissue showed maximal BSCB disruption at 24 h postinjury, with significant disruption observed until 5 days postinjury (p<0.01). FITC-LEA-identified functional vasculature was dramatically reduced by 24 h. Similarly, RECA-1 immunohistochemistry showed a significant decrease in the number of vessels at 24 h postinjury, compared to uninjured animals (p<0.01), with slight increases in endogenous revascularization by 10 days postinjury. White versus gray matter (GM) quantification showed that GM vessels are more susceptible to SCI. Finally, we observed an endogenous angiogenic response between 3 and 7 days postinjury: maximal endothelial cell proliferation was observed at day 5. These data indicate that BSCB disruption and endogenous revascularization occur at specific time points after injury, which may be important for developing effective therapeutic interventions for SCI.

摘要

脊髓损伤(SCI)后会发生显著的血管变化,这会导致病情进行性发展。在本研究中,我们使用雌性Wistar大鼠(300 - 350克),并在T6至T7处进行35克的夹压损伤,以描述SCI后随之发生的血管变化的空间和时间特征。在处死动物前,分别注射血管示踪染料(2%伊文思蓝(EB)或异硫氰酸荧光素/番茄凝集素[FITC - LEA])来评估血脊髓屏障(BSCB)的完整性或血管结构。EB组织的分光光度法显示,损伤后24小时BSCB破坏最大,直至损伤后5天仍观察到显著破坏(p<0.01)。FITC - LEA识别的功能性脉管系统在24小时时显著减少。同样,RECA - 1免疫组织化学显示,与未受伤动物相比,损伤后24小时血管数量显著减少(p<0.01),损伤后10天内源性血管再生略有增加。白质与灰质(GM)的定量分析表明,GM血管更容易受到SCI的影响。最后,我们观察到损伤后3至7天内有内源性血管生成反应:在第5天观察到最大程度的内皮细胞增殖。这些数据表明,BSCB破坏和内源性血管再生在损伤后的特定时间点发生,这可能对开发有效的SCI治疗干预措施很重要。

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