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

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

doi:10.1186/s12987-018-0098-1

Cited by 35 publications

(47 citation statements)

References 52 publications

(87 reference statements)

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“…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][32][33]. In our model, CSF flow was blocked due to extradural compression.…”

Section: Discussionmentioning

confidence: 84%

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

Yao

Zhang

et al. 2020

Fluids Barriers CNS

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Background: Syringomyelia is a common spinal cord lesion. However, whether CSF blockage is linked to the formation and enlargement of syringomyelia is still controversial. The current model of syringomyelia needs modification to more closely mimic the clinical situation. Methods: We placed cotton strips under the T13 lamina of 40 8-week-old rats and blocked CSF flow by extradural compression. After 4 and 8 weeks, MRI was performed to evaluate the morphology of syringomyelia and the ratio of spinal cord diameter to syrinx diameter calculated. Locomotor function was evaluated weekly. Spinal cord sections, staining and immunohistochemistry were performed 8 weeks after surgery, the ratio of the central canal to the spinal cord area was calculated, and ependymal cells were counted. In another experiment, we performed decompression surgery for 8 rats with induced syringomyelia at the 8th week after surgery. During the surgery, the cotton strip was completely removed without damaging the dura mater. Then, the rats received MRI imaging during the following weeks and were sacrificed for pathological examination at the end of the experiment. Results: Syringomyelia formed in 82.5% (33/40) of rats at the 8-week follow-up. The Basso, Beattie and Bresnahan (BBB) scores of rats in the experimental group decreased from 21.0±0.0 to 18.0 ±3.9 in the first week after operation but returned to normal in later weeks. The BBB score indicated that the locomotor deficit caused by compression is temporary and can spontaneously recover. MRI showed that the syrinx is located in the center of the spinal cord, which is very similar to the most common syringomyelia in humans. The ratio of the central canal to the spinal cord area reached (2.9 ± 2.0) × 10 −2 , while that of the sham group was (5.4 ± 1.5) × 10 −4. The number of ependymal cells lining the central canal was significantly increased (101.9 ± 39.6 vs 54.5 ± 3.4). There was no syrinx or proliferative inflammatory cells in the spinal cord parenchyma. After decompression, the syringomyelia size decreased in 50% (4/8) of the rats and increased in another 50% (4/8). Conclusion: Extradural blockade of CSF flow can induce syringomyelia in rats. Temporary locomotor deficit occurred in some rats. This reproducible rat model of syringomyelia, which mimics syringomyelia in humans, can provide a good model for the study of disease mechanisms and therapies.

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Section: Discussionmentioning

confidence: 84%

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

Yao

Zhang

et al. 2020

Fluids Barriers CNS

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“…This study has provided strong evidence for a normal flow of CSF to the caudal aspect of the spine within the CC in mice. The direction of the flow of CSF within the CC is a controversial topic, as conflicting data have been published in the past (Bradbury and Lathem, 1965; Milhorat et al, 1991; Cifuentes et al, 1992; Liu et al, 2018). Our conclusion of a caudally directed flow is in close agreement with Bradbury and Lathem (1965) using rabbits and subsequent work in guinea pigs and rats (Nakayama, 1976; Cifuentes et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, CSF freshly produced by the choroid plexuses has access to the spine through the central canal (CC) through an aperture on the floor of the fourth ventricle. The direction of flow of CSF in either the spinal SAS (Ishibashi, 1959; Di Chiro, 1966; Davson and Segal, 1996) or the CC (Bradbury and Lathem, 1965; Milhorat et al, 1991; Cifuentes et al, 1992; Liu et al, 2018) is controversial. Most of these studies were performed under anesthetized, immobilized conditions, which limits CSF circulation (Ma et al, 2019), or involved direct injections of tracers into the intrathecal space, which may artificially induce nonphysiological tracer distribution.…”

Section: Introductionmentioning

confidence: 99%

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Decker

Müller

et al. 2019

Journal of Experimental Medicine

106

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The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.

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“…It should also be noted that there may be regional variations, see e.g. [ 66 , 67 ]). The idea that the basement membranes of microvessels can provide a preferential route stems from observations that when horseradish peroxidase is introduced into CSF with consequential influx along arteries the peroxidase is found to be localized in the basement membranes around microvessels.…”

Section: Perivascular Pathwaysmentioning

confidence: 99%

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

Hladky

Barrand

2018

Fluids Barriers CNS

165

156

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This review considers efflux of substances from brain parenchyma quantified as values of clearances (CL, stated in µL g−1 min−1). Total clearance of a substance is the sum of clearance values for all available routes including perivascular pathways and the blood–brain barrier. Perivascular efflux contributes to the clearance of all water-soluble substances. Substances leaving via the perivascular routes may enter cerebrospinal fluid (CSF) or lymph. These routes are also involved in entry to the parenchyma from CSF. However, evidence demonstrating net fluid flow inwards along arteries and then outwards along veins (the glymphatic hypothesis) is still lacking. CLperivascular, that via perivascular routes, has been measured by following the fate of exogenously applied labelled tracer amounts of sucrose, inulin or serum albumin, which are not metabolized or eliminated across the blood–brain barrier. With these substances values of total CL ≅ 1 have been measured. Substances that are eliminated at least partly by other routes, i.e. across the blood–brain barrier, have higher total CL values. Substances crossing the blood–brain barrier may do so by passive, non-specific means with CLblood-brain barrier values ranging from < 0.01 for inulin to > 1000 for water and CO2. CLblood-brain barrier values for many small solutes are predictable from their oil/water partition and molecular weight. Transporters specific for glucose, lactate and many polar substrates facilitate efflux across the blood–brain barrier producing CLblood-brain barrier values > 50. The principal route for movement of Na+ and Cl− ions across the blood–brain barrier is probably paracellular through tight junctions between the brain endothelial cells producing CLblood-brain barrier values ~ 1. There are large fluxes of amino acids into and out of the brain across the blood–brain barrier but only small net fluxes have been observed suggesting substantial reuse of essential amino acids and α-ketoacids within the brain. Amyloid-β efflux, which is measurably faster than efflux of inulin, is primarily across the blood–brain barrier. Amyloid-β also leaves the brain parenchyma via perivascular efflux and this may be important as the route by which amyloid-β reaches arterial walls resulting in cerebral amyloid angiopathy.Electronic supplementary materialThe online version of this article (10.1186/s12987-018-0113-6) contains supplementary material, which is available to authorized users.

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

Cited by 35 publications

References 52 publications

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

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

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

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