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

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

doi:10.1186/s12987-018-0098-1

Shinuo Liu, Marcus A Stoodley + Show 4 more

Open Access

https://doi.org/10.1186/s12987-018-0098-1

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Abstract

BackgroundCerebrospinal 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.MethodsA 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.ResultsFluorescent 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.ConclusionsThese 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.

Highlights

Cerebrospinal fluid (CSF) is thought to flow into the brain via perivascular spaces around arteries, where it mixes with interstitial fluid
Rostral–caudal tracer distribution In macroscopic fluorescent imaging, tracer was observed to be localised to the injection site in all experiments (Fig. 1b)
Central canal Fluorescent tracer was detected in the central canal ependymal cell layer in 6 of 12 grey matter injections

Summary

Introduction

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. Fluid dynamics have been studied in the brain, little is known about spinal cord fluid inflow and outflow. We aimed to determine the fluid outflow pathways in the rat spinal cord. Details of the circulation of cerebrospinal fluid (CSF) and interstitial fluid (ISF) of the central nervous system remain controversial [1, 2]. The “glymphatic” theory of fluid homeostasis posits that fluid flow into and out of the parenchyma is via arterial and venular pathways respectively [10, 16, 17]. Studies to date have largely focused on the brain, with few investigations of spinal cord.

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