The Human Central Canal of the Spinal Cord: A Comprehensive Review of its Anatomy, Embryology, Molecular Development, Variants, and Pathology

Saker, Erfanul; Henry, Brandon Michael; Tomaszewski, Krzysztof A.; Loukas, Marios; Iwanaga, Joe; Oskouian, Rod J.; Tubbs, R. Shane

doi:10.7759/cureus.927

Cited by 17 publications

(21 citation statements)

References 31 publications

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“…Dorsal outlets for the fluid in the CC with connections from the filum terminale internum to the SAS have been identified in the sacral spine in rats, rabbits, guinea pigs, and rhesus monkeys (Leduc et al, 1956; Bradbury and Lathem, 1965; Nakayama, 1976). In humans, a normal flow within this anatomic space is often paid little heed, as it is believed that CC is occluded after the third decade of life (Saker et al, 2016). This is despite the well-known association between dilated CCs and the development of syringomyelia (Gardner and Goodall, 1950; Williams and Bentley, 1980).…”

Section: Resultsmentioning

confidence: 99%

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Decker

Müller

et al. 2019

Journal of Experimental Medicine

101

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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Section: Resultsmentioning

confidence: 99%

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Decker

Müller

et al. 2019

Journal of Experimental Medicine

101

106

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“…When knock-in mouse targeted to the mouse FoxJ1 locus was used, the differentiation potential of SCEp cells was shown to be extremely limited (Ren et al, 2017). This discrepancy may be attributable to the differences between species regarding the cytoarchitecture of progenitor cell niche or the function of NSCs or neural progenitor cells (Alfaro-Cervello et al, 2012Chandran et al, 2004;Garcia-Ovejero et al, 2015;Hamilton et al, 2009;Saker et al, 2016). This discrepancy may be attributable to the differences between species regarding the cytoarchitecture of progenitor cell niche or the function of NSCs or neural progenitor cells (Alfaro-Cervello et al, 2012Chandran et al, 2004;Garcia-Ovejero et al, 2015;Hamilton et al, 2009;Saker et al, 2016).…”

Section: Differentiation Potential Of Scep Cellsmentioning

confidence: 99%

“…Indeed, human GFAP promoter enables more broader expression, where GFAP-negative neural progenitor cells express the reporter gene in addition to GFAP-positive mature astrocytes (Andrae et al, 2001;Casper & Mccarthy, 2006;Malatesta, Hartfuss, & Gotz, 2000;Malatesta et al, 2003). This discrepancy may be attributable to the differences between species regarding the cytoarchitecture of progenitor cell niche or the function of NSCs or neural progenitor cells (Alfaro-Cervello et al, 2012Chandran et al, 2004;Garcia-Ovejero et al, 2015;Hamilton et al, 2009;Saker et al, 2016). Even in the very rare case, we observed the data suggesting astrocyte differentiation of a SCEp cell in the intact condition (Figure 3b and Supporting Information Figure S1b), but other studies concluded that it is unlikely.…”

Section: Proliferation Of Scep Cellsmentioning

confidence: 99%

Intracellular signaling similarity reveals neural stem cell‐like properties of ependymal cells in the adult rat spinal cord

2018

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Proliferation of ependymal cells of the adult spinal cord (SCEp cells) in the intact condition has been considered as a quite rare event. To visualize proliferating/proliferated SCEp cells, we used the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method to find that about two cells in the ependymal layer incorporated BrdU in a 10-μm-thick section. Because these two cells were not considered to undergo further proliferation, we analyzed the positioning and motility of two neighboring BrdU-incorporated proliferated cells and elucidated the tendency of the movement of SCEp cells to the outer side inside the ependymal layer. Even if it was rare, one of the proliferated cells in the ependymal layer differentiated into astrocytes. Gene introduction of Notch intracellular domain (NICD), a constitutively active form of Notch1, into SCEp cells demonstrated both increase in proliferation and induction of differentiation into astrocytes. Overexpression of Sox2 promoted proliferation in SCEp cells. The reaction of gene introduction of NICD and Sox2 indicates the similarity of intracellular signaling between SCEp cells and neural stem cells. Also, considering the fact that SCEp cells express these two factors in the intact condition, Notch and Sox2 are important for the cell fate control of SCEp cells in the intact condition.

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“…The rostral and caudal ends close off on embryonic days 25 and 27, respectively, whereby the neural canal becomes the ventricular system. Further neural tube thickening decreases the size of the neural canal until the central canal of the spinal cord is minute 33 . A single layer of columnar ependymal cells comprise the wall of the neural tube, and during development give rise to all neural tissue in the spinal cord through neuroblast and glioblast formation 32 .…”

Section: Anatomymentioning

confidence: 99%

“…The central canal has long been thought to be completely eliminated by adulthood 38,39 through a gradual closing off of the CSF-containing tube 40 via occlusion by ependymal cell debris 30,31,41 . It remains open and relatively unobstructed until the second decade of life 33 . The majority of the central canal is elliptical 42 , although variations exist including dilations, outpouches and forkings 43,44 .…”

Section: Anatomymentioning

confidence: 99%

Electrophysiological Profile of Differentiating Human Central Canal Ependymal Stem-Progenitor Cells

Malone¹

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Following spinal cord injury (SCI), current treatments look to halt the spread of tissue damage to minimize pain, with limited effectiveness. Unfortunately, there is no widely used approach for promoting re-growth across the lesion site, a necessity for functional recovery. To that end, stem cell transplant and niche manipulation therapies are a promising tool for repairing damage from SCI and other neurodegenerative conditions. As most stem cell studies are based exclusively on animal models, we aimed to address several gaps in understanding that are fundamental for potential translation to humans. Since immunocytochemistry alone cannot adequately determine whether stem cells have differentiated into mature neurons, we used patchclamp electrophysiology to assess the passive and active electrical properties of stem cells from the central canal of the spinal cord throughout the in vitro differentiation process. Rat ependymal-stem progenitor cells (epSPCs) differentiate towards a majority astrocytic fate under intrinsic differentiation conditions in vitro. Human epSPCs, on the other hand, differentiate towards a majority neuronal fate. Electrophysiological recordings of these cells in intrinsic FBScontaining differentiation media and under BDNF-, GDNF-and RA-guided differentiation show no action potential firing from two to ten weeks in vitro. Passive membrane properties fail to reach that of typical mature neurons within this time frame. Surprisingly, the vast majority of cells showed voltage-dependent spontaneous synaptic currents with reversal near 0 mV, outward rectification, and decay kinetics that are consistent with excitatory glutamatergic responses. Further studies investigating the necessary timeline and the most effective differentiation media required for development of active membrane properties are needed, as is identification of the receptor subtypes responsible for the observed synaptic currents. This will help inform future transplant and stem cell niche manipulation strategies for the treatment of human neurological disorders.iii

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The Human Central Canal of the Spinal Cord: A Comprehensive Review of its Anatomy, Embryology, Molecular Development, Variants, and Pathology

Cited by 17 publications

References 31 publications

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Intracellular signaling similarity reveals neural stem cell‐like properties of ependymal cells in the adult rat spinal cord

Electrophysiological Profile of Differentiating Human Central Canal Ependymal Stem-Progenitor Cells

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