Abstract
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.
Highlights
Fluid homeostasis in the central nervous system (CNS) is essential for normal neurological function
Our electron microscopic investigations of ultrathin sections of the spinal cord indicated that perivascular spaces were associated with all arterioles and venules, throughout the peripheral white matter and central grey matter of the spinal cord parenchyma
This study investigated the ultrastructure of perivascular spaces in the rat spinal cord as well as their physiological role in the transport of cerebrospinal fluid in the CNS
Summary
Fluid homeostasis in the central nervous system (CNS) is essential for normal neurological function. The flow pathways of cerebrospinal fluid in the spinal cord have been previously investigated using a combination of small molecular weight tracers, light and electron microscopic methods, but with the focus on flow in the central canal rather than the perivascular spaces[4,5,11]. The circulation of the CSF along the central canal of the spinal cord and its penetration into the parenchyma along perivascular spaces have been described as rapid in some studies[3,5,11], while others reported the bulk flow of fluid, within perivascular spaces of both arteries and veins, as slow and variable in its direction[15]. The physiological role of these structures in the transport of CSF and solutes was studied using a range of CSF tracers
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