Fluid outflow in the rat spinal cord: the role of perivascular and paravascular pathways

Shinuo Liu, Magdalena A. Lam, Alisha Sial, Sarah J. Hemley, Lynne E. Bilston, Marcus A. Stoodley

Cerebrospinal fluid (CSF) is thought to flow into the brain via perivascular spaces around arteries, where it mixes with interstitial fluid. The precise details concerning fluid outflow remain controversial. Although fluid dynamics have been studied in the brain, little is known about spinal cord fluid inflow and outflow. Understanding the normal fluid physiology of the spinal cord may give insight into the pathogenesis of spinal cord oedema and CSF disorders such as syringomyelia. We therefore aimed to determine the fluid outflow pathways in the rat spinal cord. A fluorescent tracer, Alexa-Fluor®-647 Ovalbumin, was injected into the extracellular space of either the cervicothoracic lateral white matter or the grey matter in twenty-two Sprague-Dawley rats over 250 s. The rats were sacrificed at 20 or 60 min post injection. Spinal cord segments were sectioned and labelled with vascular antibodies for immunohistochemistry. Fluorescent tracer was distributed over two to three spinal levels adjacent to the injection site. In grey matter injections, tracer spread radially into the white matter. In white matter injections, tracer was confined to and redistributed along the longitudinal axonal fibres. Tracer was conducted towards the pial and ependymal surfaces along vascular structures. There was accumulation of tracer around the adventitia of the intramedullary arteries, veins and capillaries, as well as the extramedullary vessels. A distinct layer of tracer was deposited in the internal basement membrane of the tunica media of arteries. In half the grey matter injections, tracer was detected in the central canal. These results suggest that in the spinal cord interstitial fluid movement is modulated by tissue diffusivity of grey and white matter. The central canal, and the compartments around or within blood vessels appear to be dominant pathways for fluid drainage in these experiments. There may be regional variations in fluid outflow capacity due to vascular and other anatomical differences between the grey and white matter.