Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, NSW 2109, Australia.
Macquarie University Microscopy Unit, Faculty of Science and Engineering, Macquarie University, New South Wales, NSW 2109, Australia.
Sci Rep. 2017 Oct 10;7(1):12924. doi: 10.1038/s41598-017-13455-4.
Perivascular spaces play a pivotal role in the exchange between cerebrospinal and interstitial fluids, and in the clearance of waste in the CNS, yet their precise anatomical components are not well described. The aim of this study was to characterise the ultrastructure of perivascular spaces and their role in the transport of fluid, in the spinal cord of healthy rats, using transmission electron microscopy. The distribution of cerebrospinal fluid tracers injected into the subarachnoid space was studied using light, confocal and electron microscopy. Perivascular spaces were found around arterioles and venules, but not capillaries, throughout the spinal cord white and grey matter. They contained fibroblasts and collagen fibres, and were continuous with the extracellular spaces of the surrounding tissue. At 5 min post injection, tracers were seen in the subarachnoid space, the peripheral white matter, the perivascular spaces, basement membranes, extracellular spaces of the surrounding tissue, and surprisingly, in the lumen of blood vessels, suggesting trans-vascular clearance. These findings point out an unrecognised outflow pathway for CNS fluids, with potential implications for volume regulation in health and disease states, but also clinically for the detection of CNS-derived biomarkers in plasma, the immune response and drug pharmacokinetics.
血管周围间隙在脑脊髓液和间质液之间的交换以及中枢神经系统废物的清除中起着关键作用，但它们的确切解剖成分尚未得到很好的描述。本研究旨在使用透射电子显微镜研究健康大鼠脊髓中血管周围间隙的超微结构及其在液体转运中的作用。通过光镜、共聚焦显微镜和电子显微镜研究了注入蛛网膜下腔的脑脊液示踪剂的分布。在脊髓白质和灰质中，均发现血管周围间隙围绕着小动脉和小静脉，但不围绕毛细血管。它们包含成纤维细胞和胶原纤维，并与周围组织的细胞外空间相连。在注射后 5 分钟，示踪剂可见于蛛网膜下腔、外周白质、血管周围间隙、基底膜、周围组织的细胞外空间，以及令人惊讶的是血管腔中，提示跨血管清除。这些发现指出了一种未被识别的中枢神经系统液体流出途径，这可能对健康和疾病状态下的体积调节有影响，但也可能对检测血浆中的中枢神经系统衍生生物标志物、免疫反应和药物药代动力学有临床意义。
