Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, 511 South Floyd Street, Louisville, KY 40292, USA.
Curr Neurovasc Res. 2010 Aug;7(3):238-50. doi: 10.2174/156720210792231840.
The endothelial-specific expression of plasmalemmal vesicle associated protein-1 (PV-1) is typical of fenestrated endothelium observed in pulmonary capillaries and some endocrine organs. In the central nervous system (CNS) it is expressed during development but disappears concomitant with maturation of the blood-CNS barrier [1]. Consistent with observations made in models of stroke, Alzheimer's disease, and tumorigenesis, we show PV-1 expression in the spinal cord specifically upregulated by pathologically-activated endothelial cells (ECs) in response to traumatic spinal cord injury (SCI). Adult female C57Bl/6 mice received a moderate T9/10 contusive SCI. PV-1 assessed by qRT-PCR and immunohistochemistry 3 hours to 14 days post-injury showed expression as early as 1 day post-SCI, with levels decreasing by 14 days. This expression was associated with microvessels in the injury epicenter and penumbral zone, with the time course and distribution correlated with progressing peripheral inflammatory cell infiltration. PV-1-immunoreactive ECs were angiogenic as demonstrated by intravascular binding of Griffonia simplicifolia isolectin B4 (IB4). ECs expressing high levels of PV-1 were anatomically and physiologically abnormal with altered/absent immunostaining for occludin and zonula occludens-1 (ZO-1), and decreased expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4). Glucose transporter type I (Glut-1) expression decreased in affected, PV-1 positive microvessels with little colocalization of PV-1 and Glut-1 apparent by 7 days post-SCI. These data suggest that upregulation of microvascular expression of PV-1 post-SCI may promote major components of secondary injury including extravasation of cellular and acellular mediators of inflammation and may accelerate loss of neuropil and decline in the functional and anatomical integrity of the neurovascular unit (NVU).
质膜小泡相关蛋白-1（PV-1）在肺毛细血管和一些内分泌器官中观察到的窗孔内皮中特异性表达。在中枢神经系统（CNS）中，它在发育过程中表达，但伴随着血脑屏障的成熟而消失[1]。与中风、阿尔茨海默病和肿瘤发生模型中的观察结果一致，我们显示 PV-1 在脊髓中的表达在病理性激活的内皮细胞（EC）中特异性上调，以响应创伤性脊髓损伤（SCI）。成年雌性 C57Bl/6 小鼠接受 T9/10 中度挫伤性 SCI。通过 qRT-PCR 和免疫组织化学评估 3 小时至 14 天后的损伤，发现 PV-1 在 SCI 后 1 天即可表达，到 14 天表达水平降低。这种表达与损伤中心和半影区的微血管有关，其时间过程和分布与外周炎症细胞浸润的进展相关。PV-1 免疫反应性 EC 具有血管生成能力，这通过 Griffonia simplicifolia 同工凝集素 B4（IB4）的血管内结合得到证明。表达高水平 PV-1 的 EC 在解剖学和生理学上是异常的，其紧密连接蛋白和闭合蛋白-1（ZO-1）的免疫染色改变/缺失，以及神经胶质纤维酸性蛋白（GFAP）和水通道蛋白-4（AQP4）的表达降低。受影响的、PV-1 阳性微血管中的葡萄糖转运蛋白 1（Glut-1）表达降低，SCI 后 7 天，PV-1 和 Glut-1 的共定位很少。这些数据表明，SCI 后微血管中 PV-1 的上调可能促进继发性损伤的主要成分，包括细胞和无细胞炎症介质的渗出，并可能加速神经突的丧失和神经血管单元（NVU）的功能和解剖完整性的下降。
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