Center of Excellence for Aging & Brain Repair, University of South Florida, Morsani College of Medicine, Tampa, FL 33612, USA.
Brain Res. 2012 Aug 21;1469:114-28. doi: 10.1016/j.brainres.2012.05.056. Epub 2012 Jun 27.
Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets.
血管病理学，包括血脑/脊髓屏障（BBB/BSCB）的改变，最近被认为是可能加重运动神经元损伤的关键因素，为 ALS 确定了神经血管疾病的特征。然而，散发性 ALS（SALS）中的 BBB/BSCB 功能仍未确定。在这项研究中，研究了 SALS 患者和对照组死后延髓和脊髓组织的灰质和白质中的 BBB/BSCB 完整性。主要发现包括：（1）内皮细胞损伤和周细胞变性；（2）严重的细胞内和细胞外水肿；（3）内皮细胞中 CD31 和 CD105 表达减少；（4）血管周围胶原 IV 和纤维蛋白沉积显著增加；（5）腰椎脊髓中的微血管密度显著增加；（6）IgG 微血管渗漏；（7）紧密连接和黏附蛋白表达减少。在 SALS 患者的延髓、颈段和腰段脊髓的灰质和白质中确定的微血管屏障异常是新的发现。在 ALS 中发现的普遍的屏障损伤可能对疾病的发病机制和进展以及发现新的治疗靶点具有重要意义。
