Effect of extradural constriction on CSF flow in rat spinal cord

Abstract

BackgroundFluid homeostasis in the central nervous system (CNS) is essential for normal neurological function. Cerebrospinal fluid (CSF) in the subarachnoid space and interstitial fluid circulation in the CNS parenchyma clears metabolites and neurotransmitters and removes pathogens and excess proteins. A thorough understanding of the normal physiology is required in order to understand CNS fluid disorders, including post-traumatic syringomyelia. The aim of this project was to compare fluid transport, using quantitative imaging of tracers, in the spinal cord from animals with normal and obstructed spinal subarachnoid spaces.MethodsA modified extradural constriction model was used to obstruct CSF flow in the subarachnoid space at the cervicothoracic junction (C7–T1) in Sprague–Dawley rats. Alexa-Fluor 647 Ovalbumin conjugate was injected into the cisterna magna at either 1 or 6 weeks post–surgery. Macroscopic and microscopic fluorescent imaging were performed in animals sacrificed at 10 or 20 min post–injection. Tracer fluorescence intensity was compared at cervical and thoracic spinal cord levels between control and constriction animals at each post-surgery and post-injection time point. The distribution of tracer around arterioles, venules and capillaries was also compared.ResultsMacroscopically, the fluorescence intensity of CSF tracer was significantly greater in spinal cords from animals with a constricted subarachnoid space compared to controls, except at 1 week post-surgery and 10 min post-injection. CSF tracer fluorescence intensity from microscopic images was significantly higher in the white matter of constriction animals 1 week post surgery and 10 min post-injection. At 6 weeks post–constriction surgery, fluorescence intensity in both gray and white matter was significantly increased in animals sacrificed 10 min post-injection. At 20 min post-injection this difference was significant only in the white matter and was less prominent. CSF tracer was found predominantly in the perivascular spaces of arterioles and venules, as well as the basement membrane of capillaries, highlighting the importance of perivascular pathways in the transport of fluid and solutes in the spinal cord.ConclusionsThe presence of a subarachnoid space obstruction may lead to an increase in fluid flow within the spinal cord tissue, presenting as increased flow in the perivascular spaces of arterioles and venules, and the basement membranes of capillaries. Increased fluid retention in the spinal cord in the presence of an obstructed subarachnoid space may be a critical step in the development of post-traumatic syringomyelia.Electronic supplementary materialThe online version of this article (10.1186/s12987-019-0127-8) contains supplementary material, which is available to authorized users.

Abnormalities in spinal cord ultrastructure in a rat model of post-traumatic syringomyelia

“…CSF flow obstruction in the spinal subarachnoid space has been suggested to increase pressure and thus force fluid into the cord [9][10][11]. Indeed, in a recent rodent study, a spinal subarachnoid space obstruction increased CSF tracer penetration in spinal cord tissue [12]. This finding aligns with the observation that most post-traumatic syrinxes are associated with narrowing or obstruction of the spinal subarachnoid space [2].…”

“…2). Enlarged perivascular spaces are hypothesized to occur from perturbations to subarachnoid CSF flow, and may increase the fluid load of the cord [12]. Indeed, enlarged perivascular spaces have been observed in syringomyelia in human [43], and in animal models [16,20].…”

Chronic extradural compression of spinal cord leads to syringomyelia in rat model

“…These diseases all lead to changes in the fluid dynamics of CSF in the subarachnoid space, thus favoring the flow of CSF from the subarachnoid space into the central canal [ 29 , 30 ]. Some studies have confirmed that CSF passes through the spinal cord to communicate between the subarachnoid space and central canal [ 13 , 26 , 31 – 33 ]. In our model, CSF flow was blocked due to extradural compression.…”

High‐resolution Micro‐CT Myelography to Assess Spinal Subarachnoid Space Changes After Spinal Cord Injury in Rats

“…We still do not understand why only some nerve roots in some of the animals were observed. Although it has been described that experimental SSAS obstruction may result in disruption of cervical lymphatic drainage at spinal nerve root sheaths, 25 we found no relationship between the observability of roots and experimental groups. We speculate that variables such as anatomical variants of the nerve root sheath, 24,26 variations in breathing conditions, 27 and differences in intrathecal pressure could be involved in the selectivity of neuroimaging nerve root enhancement.…”