On the role of ependymal disruption in neurodegeneration
Friday, 08 October 2004 00:00
Author: Milan Radojicic MD
[...]
Ependymal Disruption in Neurodegeneration
Consequences of ependymal ciliary loss. Cilia are specialized projections of
ependymal cells and their beating promotes the flow of CSF within the central canal.
Ependymal ciliary loss is known to predispose to hydrocephalus (Afzelius, 2004) and is a
feature of the disease (Kiefer et al., 1998). Therefore, this loss of ependymal cell cilia
may result in a local stasis and accumulation of CSF, with subsequent central canal
dilation, accumulation of toxic metabolites and damage to the ependymal and
periependymal regions and ultimately the brain parenchyma. For example, loss of ependymal
Consequences of ependymal ciliary loss. Cilia are specialized projections of
ependymal cells and their beating promotes the flow of CSF within the central canal.
Ependymal ciliary loss is known to predispose to hydrocephalus (Afzelius, 2004) and is a
feature of the disease (Kiefer et al., 1998). Therefore, this loss of ependymal cell cilia
may result in a local stasis and accumulation of CSF, with subsequent central canal
dilation, accumulation of toxic metabolites and damage to the ependymal and
periependymal regions and ultimately the brain parenchyma. For example, loss of ependymal
ciliary structure and function in Alzheimer's Disease may lead to stasis of cerebrospinal fluid
in the ventricles thereby altering the clearance of extracellular fluid, proteins and metabolites in the brain
parenchyma leading to the accumulation of plaques in the brain tissue (a process that
could be thought of as "protein-neuria"). Notably, the ependymal cell layer disruption
noted in our studies is reminiscent of the ependymal denudation that proceeds the development
of severe hydrocephalus in the hyh mouse (Jimenez et al., 2001).
Consequences of ependymal denudation. Normally, the ependyma consists of a
pseudostratified monolayer of cells that plays an important role in CSF homeostastis by
regulating fluid and electrolyte balance between the CSF and neuropil (Bruni, 1998).
Disruption of the ependymal layer could therefore result in the loss of a protective
epithelium and incompetence of the central canal, leading to an exposure of the adjacent
grey and white matter to pressure gradients and an eventual dissection of stagnant CSF
from within the canal. Indeed, fluid from syrinxes are are known to differ from normal
CSF (Levine, 2004), usually having a higher protein content(Rossier et al., 1985), which
may give rise to oncotic pressures analogous to that seen in chronic subdural fluid
collections. Prolonged exposure of peri-ependymal tissues to this microenvironment may
lead to structural degeneration as well as functional deficits, such as conduction failures.
Indeed, areas of ependymal denudation were consistently opposed to focal regions of
peri-ependymal edema, gliosis, macrophage infiltration and loss of neuropil. Finally,
local disruptions of the blood brain barrier may contribute to the edema (Levine, 2004),
but also may represent a source of inflammatory molecules and plasma proteins that may
adversely influence the microenvironment of nearby cells, including cells with
stem/progenitor characteristics, thereby influencing their viability and patterns of
differentiation.
Disruption of the ependymal region stem cell niche. Cells of the ependymal region
are vestiges of neuroepithelial cells that gave rise to neurons and glia during mammalian
development (Vaquero et al., 1981) and are known to orchestrate the regenerative
response in tailed amphibians (Chernoff et al., 2003). Ependymal region cells have been
shown to proliferate (Bruni and Anderson, 1987;Matthews et al., 1979;Takahashi et al.,
2003;Vaquero et al., 1981) and migrate (Johansson et al., 1999;Kojima and Tator,
2002;Mothe and Tator, 2005) following spinal cord injury. This finding has led some
authors to speculate on their role in endogenous repair in humans (Beattie et al., 1997).
Indeed, the kinetics of ependymal region cell proliferation and differentiation have been
correlated with the recovery of lower limb motor function in rats following contusion
injuries (Takahashi et al., 2003). Of note, neural stem cells have been isolated from the
CNS (Johansson et al., 1999;Weiss et al., 1996;Yamamoto et al., 2001), including regions
near the central canal (Martens et al., 2002). Unlike the SVZ, the prototypical stem cell
niche of the CNS (for a review, see Doetsch, 2003), multipotent cells of the ependymal
region of the spinal cord appear restricted to glial lineages (Johansson et al., 1999; Mothe
Consequences of ependymal denudation. Normally, the ependyma consists of a
pseudostratified monolayer of cells that plays an important role in CSF homeostastis by
regulating fluid and electrolyte balance between the CSF and neuropil (Bruni, 1998).
Disruption of the ependymal layer could therefore result in the loss of a protective
epithelium and incompetence of the central canal, leading to an exposure of the adjacent
grey and white matter to pressure gradients and an eventual dissection of stagnant CSF
from within the canal. Indeed, fluid from syrinxes are are known to differ from normal
CSF (Levine, 2004), usually having a higher protein content(Rossier et al., 1985), which
may give rise to oncotic pressures analogous to that seen in chronic subdural fluid
collections. Prolonged exposure of peri-ependymal tissues to this microenvironment may
lead to structural degeneration as well as functional deficits, such as conduction failures.
Indeed, areas of ependymal denudation were consistently opposed to focal regions of
peri-ependymal edema, gliosis, macrophage infiltration and loss of neuropil. Finally,
local disruptions of the blood brain barrier may contribute to the edema (Levine, 2004),
but also may represent a source of inflammatory molecules and plasma proteins that may
adversely influence the microenvironment of nearby cells, including cells with
stem/progenitor characteristics, thereby influencing their viability and patterns of
differentiation.
Disruption of the ependymal region stem cell niche. Cells of the ependymal region
are vestiges of neuroepithelial cells that gave rise to neurons and glia during mammalian
development (Vaquero et al., 1981) and are known to orchestrate the regenerative
response in tailed amphibians (Chernoff et al., 2003). Ependymal region cells have been
shown to proliferate (Bruni and Anderson, 1987;Matthews et al., 1979;Takahashi et al.,
2003;Vaquero et al., 1981) and migrate (Johansson et al., 1999;Kojima and Tator,
2002;Mothe and Tator, 2005) following spinal cord injury. This finding has led some
authors to speculate on their role in endogenous repair in humans (Beattie et al., 1997).
Indeed, the kinetics of ependymal region cell proliferation and differentiation have been
correlated with the recovery of lower limb motor function in rats following contusion
injuries (Takahashi et al., 2003). Of note, neural stem cells have been isolated from the
CNS (Johansson et al., 1999;Weiss et al., 1996;Yamamoto et al., 2001), including regions
near the central canal (Martens et al., 2002). Unlike the SVZ, the prototypical stem cell
niche of the CNS (for a review, see Doetsch, 2003), multipotent cells of the ependymal
region of the spinal cord appear restricted to glial lineages (Johansson et al., 1999; Mothe
and Tator, 2005; Takahashi et al., 2003). Reports of gliogenesis near the central canal
include the generation of ependymal cells (Bruni and Anderson, 1987), reactive astrocytes
(Johansson et al., 1999; Mothe and Tator, 2005; Takahashi et al., 2003), oligodendrocyte
precursors (Miller and Ono, 1998) and microglia (Carbonell et al., 2005). Glia are
supportive cells of the CNS and are critical for maintaining the structural and functional
integrity of the spinal cord after injury (Hauwel et al., 2005). Even reactive astrocytes,
long thought to be inhibitory to axonal regeneration, appear to play a role in repair of SCI
lesions (Faulkner et al., 2004;Takahashi et al., 2003;Talbott et al., 2005). Therefore, it
stands to reason that disruption of the ependymal stromal epithelium, along with
periependymal stem/progenitor cells, may represent a heretofore unrecognized
pathogenic mechanism in spinal cord injury and PTS, which would hinder gliogenesis in
the ependymal region and subsequently wound repair in the spinal cord. Indeed, the
progressive disruption of this stem cell niche, through mechanical and cytotoxic means,
could represent a disease mechanism that tips the balance between injury and repair in the
spinal cord toward further cytoarchitectural destruction of lesions over time. In principle,
this conceptualized disease process should be investigated in other multipotent niches (e.g,
(Johansson et al., 1999; Mothe and Tator, 2005; Takahashi et al., 2003), oligodendrocyte
precursors (Miller and Ono, 1998) and microglia (Carbonell et al., 2005). Glia are
supportive cells of the CNS and are critical for maintaining the structural and functional
integrity of the spinal cord after injury (Hauwel et al., 2005). Even reactive astrocytes,
long thought to be inhibitory to axonal regeneration, appear to play a role in repair of SCI
lesions (Faulkner et al., 2004;Takahashi et al., 2003;Talbott et al., 2005). Therefore, it
stands to reason that disruption of the ependymal stromal epithelium, along with
periependymal stem/progenitor cells, may represent a heretofore unrecognized
pathogenic mechanism in spinal cord injury and PTS, which would hinder gliogenesis in
the ependymal region and subsequently wound repair in the spinal cord. Indeed, the
progressive disruption of this stem cell niche, through mechanical and cytotoxic means,
could represent a disease mechanism that tips the balance between injury and repair in the
spinal cord toward further cytoarchitectural destruction of lesions over time. In principle,
this conceptualized disease process should be investigated in other multipotent niches (e.g,
the brain, blood vessels, and other organs and systems) as a basis for understanding
related degenerative disorders and sequelae.
For example, radiologists have noted an early finding of Multiple Sclerosis includes changes
along the ependymal lining, the ependymal dash-dot sign. Throughout our lives the body
attempts to balance injury and repair in ourtissues. Damage to the ependymal lining
(and ependymal region stem cells) may alter the balance between injury and repair in our
bodies by eliminating our capacity to self-repair our tissues with endogenous stem cells.
Therefore, the heightened inflammatory response in the patient with multiple sclerosis may
continue unabated by endogenous repair. The relapsing/remitting form of the disorder may
represent periodic changes in the inflammatory response balanced by some intact self-repair.
[...]
Looking forward
These studies suggest ependymal region disruption as a novel pathogenic
mechanism in the progression of post-traumatic syringomyelia, identify central canal dilation
Looking forward
These studies suggest ependymal region disruption as a novel pathogenic
mechanism in the progression of post-traumatic syringomyelia, identify central canal dilation
as a potential marker of PTS and document the ependymal region as a therapeutic target,
through cellular rescue or replacement. Furthermore, these findings share many histologic
features with chronic hydrocephalus (Kiefer et al., 1998) suggesting that early restoration of
favorable CSF hydrodynamics in SCI may prevent further degeneration and provide an
environment more hospitable for repair.
environment more hospitable for repair.
Ependymal Stem cell disruption: A clue to a mechanism in neurodegeneration?
Ependymal Disruption in Alzheimer's Disease
[...]
For example, loss of ependymal ciliary structure and function in Alzheimer's Disease may lead to
stasis of cerebrospinal fluid in the ventricles thereby altering the clearance of extracellular fluid,
proteins and metabolites in the brain parenchyma leading to the accumulation of plaques in the brain
tissue (a process that could be thought of as "protein-neuria"). Disruptions in gliogenesis, such as
described in spinal cord injury, would similarly disrupt the supportive syncitial function of the brain.
Disruptions in neurogenesis would affect brain function, including cognition. Further, I posit
the stem cell niche disruption could affect the chain migration of olfactory neurons, along the
rostral migratory stream, leading to anosmia as an early sign of the disease.
Dialysis of the cerebrospinal fluid (removal of unwanted proteins and metabolites and electrolytes)
the stem cell niche disruption could affect the chain migration of olfactory neurons, along the
rostral migratory stream, leading to anosmia as an early sign of the disease.
Dialysis of the cerebrospinal fluid (removal of unwanted proteins and metabolites and electrolytes)
such as made possible with the award-winning spinal physiology device revealed on this site
could represent a temporizing treatment.
Ultimate repair of the ependymal lining (see the biological shunt) and reconstitution of local blood
would be the final cure.
Ependymal Disruption in Multiple Sclerosis
[...]
For example, radiologists have noted an early finding of Multiple Sclerosis includes changes
along the ependymal lining, the ependymal dash-dot sign. Throughout our lives the body
attempts to balance injury and repair in ourtissues. Damage to the ependymal lining
(and ependymal region stem cells) may alter the balance between injury and repair in our
bodies by eliminating our capacity to self-repair our tissues with endogenous stem cells.
Therefore, the heightened inflammatory response in the patient with multiple sclerosis may
continue unabated by endogenous repair. The relapsing/remitting form of the disorder may
represent periodic changes in the inflammatory response balanced by some intact self-repair.
Ependymal Disruption in Hydrocephalus
[...]
Ependymal Disruption in Normal Pressure Hydrocephalus
[...]
'Chemo-Brain' and endogenous stem cell dysfunction
Do cancer drugs impair endogenous stem cell function and lead to 'chemo-brain'?
Spinal Cord Transection
Does sparing of the ependyma may confer greater chances for recovery?
Ependymal disruption in ALS
...
The dictum is simple: Repair the ependyma and you will repair the brain and spinal cord.
Reference List
1. Afzelius, B. A. 2004. Cilia-related diseases. J.Pathol. 204, 470-477.
2. Beattie, M. S., Bresnahan, J. C., Komon, J., Tovar, C. A., Van, M. M., Anderson,
D. K., Faden, A. I., Hsu, C. Y., Noble, L. J., Salzman, S., Young, W. 1997.
Endogenous repair after spinal cord contusion injuries in the rat. Exp.Neurol. 148,
453-463.
3. Berkouk, K., Carpenter, P. W., Lucey, A. D. 2003. Pressure wave propagation in
fluid-filled co-axial elastic tubes. Part 1: Basic theory. J.Biomech.Eng 125, 852-
856.
4. Bhadelia, R. A., Bogdan, A. R., Kaplan, R. F., Wolpert, S. M. 1997.
Cerebrospinal fluid pulsation amplitude and its quantitative relationship to
cerebral blood flow pulsations: a phase-contrast MR flow imaging study.
Neuroradiology 39, 258-264.
5. Bilston, L. E., Fletcher, D. F., Brodbelt, A. R., Stoodley, M. A. 2003. Arterial
pulsation-driven cerebrospinal fluid flow in the perivascular space: a
computational model. Comput.Methods Biomech.Biomed.Engin. 6, 235-241.
6. Bravo, G., Guizar-Sahagun, G., Ibarra, A., Centurion, D., Villalon, C. M. 2004.
Cardiovascular alterations after spinal cord injury: an overview.
Curr.Med.Chem.Cardiovasc.Hematol.Agents 2, 133-148.
7. Brodbelt, A. R., Stoodley, M. A., Watling, A., Rogan, C., Tu, J., Brown, C. J.,
Burke, S., Jones, N. R. 2003a. The role of excitotoxic injury in post-traumatic
syringomyelia. J.Neurotrauma 20, 883-893.
8. Brodbelt, A. R., Stoodley, M. A., Watling, A. M., Tu, J., Burke, S., Jones, N. R.
2003b. Altered subarachnoid space compliance and fluid flow in an animal model
of posttraumatic syringomyelia. Spine 28, E413-E419.
9. Brodbelt, A. R., Stoodley, M. A., Watling, A. M., Tu, J., Jones, N. R. 2003c.
Fluid flow in an animal model of post-traumatic syringomyelia. Eur.Spine J. 12,
300-306.
10. Bruni, J. E. 1998. Ependymal development, proliferation, and functions: a review.
Microsc.Res.Tech. 41, 2-13.
11. Bruni, J. E., Anderson, W. A. 1987. Ependyma of the rat fourth ventricle and
central canal: response to injury. Acta Anat.(Basel) 128, 265-273.
12. Carbonell, W. S., Murase, S. I., Horwitz, A. F., Mandell, J. W. 2005. Infiltrative
microgliosis: activation and long-distance migration of subependymal microglia
following periventricular insults. J.Neuroinflammation. 2, 5.
13. Carpenter, P. W., Berkouk, K., Lucey, A. D. 2003. Pressure wave propagation in
fluid-filled co-axial elastic tubes. Part 2: Mechanisms for the pathogenesis of
syringomyelia. J.Biomech.Eng 125, 857-863.
14. Chang, H. S., Nakagawa, H. 2004. Theoretical analysis of the pathophysiology of
syringomyelia associated with adhesive arachnoiditis.
J.Neurol.Neurosurg.Psychiatry 75, 754-757.
15. Chang, H. S., Nakagawa, H. 2003. Hypothesis on the pathophysiology of
syringomyelia based on simulation of cerebrospinal fluid dynamics.
J.Neurol.Neurosurg.Psychiatry 74, 344-347.
16. Chernoff, E. A., Stocum, D. L., Nye, H. L., Cameron, J. A. 2003. Urodele spinal
cord regeneration and related processes. Dev.Dyn. 226, 295-307.
17. Cosan, T. E., Tel, E., Durmaz, R., Gulec, S., Baycu, C. 2000. Non-hindbrainrelated
syringomyelia. Obstruction of the subarachnoid space and the central
canal in rats. An experimental study. J.Neurosurg.Sci. 44, 123-127.
18. Doetsch, F. 2003. A niche for adult neural stem cells. Curr.Opin.Genet.Dev. 13,
543-550.
19. Faulkner, J. R., Herrmann, J. E., Woo, M. J., Tansey, K. E., Doan, N. B.,
Sofroniew, M. V. 2004. Reactive astrocytes protect tissue and preserve function
after spinal cord injury. J.Neurosci. 24, 2143-2155.
20. Fischbein, N. J., Dillon, W. P., Cobbs, C., Weinstein, P. R. 1999. The "presyrinx"
state: a reversible myelopathic condition that may precede syringomyelia. AJNR
Am.J.Neuroradiol. 20, 7-20.
21. Gardner, W. J., Angel, J. 1958. The cause of syringomyelia and its surgical
treatment. Cleve.Clin.Q. 25, 4-8.
22. Hauwel, M., Furon, E., Canova, C., Griffiths, M., Neal, J., Gasque, P. 2005.
Innate (inherent) control of brain infection, brain inflammation and brain repair:
the role of microglia, astrocytes, "protective" glial stem cells and stromal
ependymal cells. Brain Res.Brain Res.Rev. 48, 220-233.
23. Houle, J. D., Tessler, A. 2003. Repair of chronic spinal cord injury. Exp.Neurol.
182, 247-260.
24. Jimenez, A. J., Tome, M., Paez, P., Wagner, C., Rodriguez, S., Fernandez-Llebrez,
P., Rodriguez, E. M., Perez-Figares, J. M. 2001. A programmed ependymal
denudation precedes congenital hydrocephalus in the hyh mutant mouse.
J.Neuropathol.Exp.Neurol. 60, 1105-1119.
25. Johansson, C. B., Momma, S., Clarke, D. L., Risling, M., Lendahl, U., Frisen, J.
1999. Identification of a neural stem cell in the adult mammalian central nervous
system. Cell 96, 25-34.
26. Kiefer, M., Eymann, R., von, T. S., Muller, A., Steudel, W. I., Booz, K. H. 1998.
The ependyma in chronic hydrocephalus. Childs Nerv.Syst. 14, 263-270.
27. Klekamp, J. 2002. The pathophysiology of syringomyelia - historical overview
and current concept. Acta Neurochir.(Wien.) 144, 649-664.
28. Klekamp, J., Volkel, K., Bartels, C. J., Samii, M. 2001. Disturbances of
cerebrospinal fluid flow attributable to arachnoid scarring cause interstitial edema
of the cat spinal cord. Neurosurgery 48, 174-185.
29. Kojima, A., Tator, C. H. 2002. Intrathecal administration of epidermal growth
factor and fibroblast growth factor 2 promotes ependymal proliferation and
functional recovery after spinal cord injury in adult rats. J.Neurotrauma 19, 223-
238.
30. Krassioukov, A. V., Weaver, L. C. 1995. Episodic hypertension due to autonomic
dysreflexia in acute and chronic spinal cord-injured rats. Am.J.Physiol 268,
H2077-H2083.
31. Lederhaus, S. C., Pritz, M. B., Pribram, H. F. 1988. Septation in syringomyelia
and its possible clinical significance. Neurosurgery 22, 1064-1067.
32. Lee, G. Y., Jones, N. R., Mayrhofer, G., Brown, C., Cleland, L. 2005. Origin of
macrophages in a kaolin-induced model of rat syringomyelia: a study using
radiation bone marrow chimeras. Spine 30, 194-200.
33. Levine, D. N. 2004. The pathogenesis of syringomyelia associated with lesions at
the foramen magnum: a critical review of existing theories and proposal of a new
hypothesis. J.Neurol.Sci. 220, 3-21.
34. Loth, F., Yardimci, M. A., Alperin, N. 2001. Hydrodynamic modeling of
cerebrospinal fluid motion within the spinal cavity. J.Biomech.Eng 123, 71-79.
35. Martens, D. J., Seaberg, R. M., van der, K. D. 2002. In vivo infusions of
exogenous growth factors into the fourth ventricle of the adult mouse brain
increase the proliferation of neural progenitors around the fourth ventricle and the
central canal of the spinal cord. Eur.J.Neurosci. 16, 1045-1057.
36. Matthews, M. A., St Onge, M. F., Faciane, C. L. 1979. An electron microscopic
analysis of abnormal ependymal cell proliferation and envelopment of sprouting
axons following spinal cord transection in the rat. Acta Neuropathol.(Berl) 45, 27-
36.
37. Menick, B. J. 2001. Phase-contrast magnetic resonance imaging of cerebrospinal
fluid flow in the evaluation of patients with Chiari I malformation. Neurosurg
Focus 11, 1-4.
38. Milhorat, T. H., Nobandegani, F., Miller, J. I., Rao, C. 1993. Noncommunicating
syringomyelia following occlusion of central canal in rats. Experimental model
and histological findings. J.Neurosurg. 78, 274-279.
39. Miller, R. H., Ono, K. 1998. Morphological analysis of the early stages of
oligodendrocyte development in the vertebrate central nervous system.
Microsc.Res.Tech. 41, 441-453.
40. Mothe, A. J., Tator, C. H. 2005. Proliferation, migration, and differentiation of
endogenous ependymal region stem/progenitor cells following minimal spinal
cord injury in the adult rat. Neuroscience 131, 177-187.
41. Rossier, A. B., Foo, D., Shillito, J., Dyro, F. M. 1985. Posttraumatic cervical
syringomyelia. Incidence, clinical presentation, electrophysiological studies,
syrinx protein and results of conservative and operative treatment. Brain 108 ( Pt
2), 439-461.
42. Schwartz, E. D., Yezierski, R. P., Pattany, P. M., Quencer, R. M., Weaver, R. G.
1999. Diffusion-weighted MR imaging in a rat model of syringomyelia after
excitotoxic spinal cord injury. AJNR Am.J.Neuroradiol. 20, 1422-1428.
43. Stoodley, M. A., Brown, S. A., Brown, C. J., Jones, N. R. 1997. Arterial
pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in
the sheep spinal cord. J.Neurosurg. 86, 686-693.
44. Stoodley, M. A., Gutschmidt, B., Jones, N. R. 1999. Cerebrospinal fluid flow in
an animal model of noncommunicating syringomyelia. Neurosurgery 44, 1065-
1075.
45. Stoodley, M. A., Jones, N. R., Brown, C. J. 1996. Evidence for rapid fluid flow
from the subarachnoid space into the spinal cord central canal in the rat. Brain
Res. 707, 155-164.
46. Storer, K. P., Toh, J., Stoodley, M. A., Jones, N. R. 1998. The central canal of the
human spinal cord: a computerised 3-D study. J.Anat. 192 ( Pt 4), 565-572.
47. Takahashi, M., Arai, Y., Kurosawa, H., Sueyoshi, N., Shirai, S. 2003. Ependymal
cell reactions in spinal cord segments after compression injury in adult rat.
J.Neuropathol.Exp.Neurol. 62, 185-194.
48. Talbott, J. F., Loy, D. N., Liu, Y., Qiu, M. S., Bunge, M. B., Rao, M. S.,
Whittemore, S. R. 2005. Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor
cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of
astrocytes. Experimental Neurology 192, 11-24.
49. Vaquero, J., Ramiro, M. J., Oya, S., Cabezudo, J. M. 1981. Ependymal reaction
after experimental spinal cord injury. Acta Neurochir.(Wien.) 55, 295-302.
50. Weiss, S., Dunne, C., Hewson, J., Wohl, C., Wheatley, M., Peterson, A. C.,
Reynolds, B. A. 1996. Multipotent CNS stem cells are present in the adult
mammalian spinal cord and ventricular neuroaxis. J.Neurosci. 16, 7599-7609.
51. Yamamoto, S., Yamamoto, N., Kitamura, T., Nakamura, K., Nakafuku, M. 2001.
Proliferation of parenchymal neural progenitors in response to injury in the adult
rat spinal cord. Exp.Neurol. 172, 115-127.
52. Yang, L., Jones, N. R., Stoodley, M. A., Blumbergs, P. C., Brown, C. J. 2001.
Excitotoxic model of post-traumatic syringomyelia in the rat. Spine 26, 1842-
1849.
© Milan Radojicic, MD 2004 - 2010. All rights reserved. This document may
not be reproduced without the expressed written permission of the author.
1. Afzelius, B. A. 2004. Cilia-related diseases. J.Pathol. 204, 470-477.
2. Beattie, M. S., Bresnahan, J. C., Komon, J., Tovar, C. A., Van, M. M., Anderson,
D. K., Faden, A. I., Hsu, C. Y., Noble, L. J., Salzman, S., Young, W. 1997.
Endogenous repair after spinal cord contusion injuries in the rat. Exp.Neurol. 148,
453-463.
3. Berkouk, K., Carpenter, P. W., Lucey, A. D. 2003. Pressure wave propagation in
fluid-filled co-axial elastic tubes. Part 1: Basic theory. J.Biomech.Eng 125, 852-
856.
4. Bhadelia, R. A., Bogdan, A. R., Kaplan, R. F., Wolpert, S. M. 1997.
Cerebrospinal fluid pulsation amplitude and its quantitative relationship to
cerebral blood flow pulsations: a phase-contrast MR flow imaging study.
Neuroradiology 39, 258-264.
5. Bilston, L. E., Fletcher, D. F., Brodbelt, A. R., Stoodley, M. A. 2003. Arterial
pulsation-driven cerebrospinal fluid flow in the perivascular space: a
computational model. Comput.Methods Biomech.Biomed.Engin. 6, 235-241.
6. Bravo, G., Guizar-Sahagun, G., Ibarra, A., Centurion, D., Villalon, C. M. 2004.
Cardiovascular alterations after spinal cord injury: an overview.
Curr.Med.Chem.Cardiovasc.Hematol.Agents 2, 133-148.
7. Brodbelt, A. R., Stoodley, M. A., Watling, A., Rogan, C., Tu, J., Brown, C. J.,
Burke, S., Jones, N. R. 2003a. The role of excitotoxic injury in post-traumatic
syringomyelia. J.Neurotrauma 20, 883-893.
8. Brodbelt, A. R., Stoodley, M. A., Watling, A. M., Tu, J., Burke, S., Jones, N. R.
2003b. Altered subarachnoid space compliance and fluid flow in an animal model
of posttraumatic syringomyelia. Spine 28, E413-E419.
9. Brodbelt, A. R., Stoodley, M. A., Watling, A. M., Tu, J., Jones, N. R. 2003c.
Fluid flow in an animal model of post-traumatic syringomyelia. Eur.Spine J. 12,
300-306.
10. Bruni, J. E. 1998. Ependymal development, proliferation, and functions: a review.
Microsc.Res.Tech. 41, 2-13.
11. Bruni, J. E., Anderson, W. A. 1987. Ependyma of the rat fourth ventricle and
central canal: response to injury. Acta Anat.(Basel) 128, 265-273.
12. Carbonell, W. S., Murase, S. I., Horwitz, A. F., Mandell, J. W. 2005. Infiltrative
microgliosis: activation and long-distance migration of subependymal microglia
following periventricular insults. J.Neuroinflammation. 2, 5.
13. Carpenter, P. W., Berkouk, K., Lucey, A. D. 2003. Pressure wave propagation in
fluid-filled co-axial elastic tubes. Part 2: Mechanisms for the pathogenesis of
syringomyelia. J.Biomech.Eng 125, 857-863.
14. Chang, H. S., Nakagawa, H. 2004. Theoretical analysis of the pathophysiology of
syringomyelia associated with adhesive arachnoiditis.
J.Neurol.Neurosurg.Psychiatry 75, 754-757.
15. Chang, H. S., Nakagawa, H. 2003. Hypothesis on the pathophysiology of
syringomyelia based on simulation of cerebrospinal fluid dynamics.
J.Neurol.Neurosurg.Psychiatry 74, 344-347.
16. Chernoff, E. A., Stocum, D. L., Nye, H. L., Cameron, J. A. 2003. Urodele spinal
cord regeneration and related processes. Dev.Dyn. 226, 295-307.
17. Cosan, T. E., Tel, E., Durmaz, R., Gulec, S., Baycu, C. 2000. Non-hindbrainrelated
syringomyelia. Obstruction of the subarachnoid space and the central
canal in rats. An experimental study. J.Neurosurg.Sci. 44, 123-127.
18. Doetsch, F. 2003. A niche for adult neural stem cells. Curr.Opin.Genet.Dev. 13,
543-550.
19. Faulkner, J. R., Herrmann, J. E., Woo, M. J., Tansey, K. E., Doan, N. B.,
Sofroniew, M. V. 2004. Reactive astrocytes protect tissue and preserve function
after spinal cord injury. J.Neurosci. 24, 2143-2155.
20. Fischbein, N. J., Dillon, W. P., Cobbs, C., Weinstein, P. R. 1999. The "presyrinx"
state: a reversible myelopathic condition that may precede syringomyelia. AJNR
Am.J.Neuroradiol. 20, 7-20.
21. Gardner, W. J., Angel, J. 1958. The cause of syringomyelia and its surgical
treatment. Cleve.Clin.Q. 25, 4-8.
22. Hauwel, M., Furon, E., Canova, C., Griffiths, M., Neal, J., Gasque, P. 2005.
Innate (inherent) control of brain infection, brain inflammation and brain repair:
the role of microglia, astrocytes, "protective" glial stem cells and stromal
ependymal cells. Brain Res.Brain Res.Rev. 48, 220-233.
23. Houle, J. D., Tessler, A. 2003. Repair of chronic spinal cord injury. Exp.Neurol.
182, 247-260.
24. Jimenez, A. J., Tome, M., Paez, P., Wagner, C., Rodriguez, S., Fernandez-Llebrez,
P., Rodriguez, E. M., Perez-Figares, J. M. 2001. A programmed ependymal
denudation precedes congenital hydrocephalus in the hyh mutant mouse.
J.Neuropathol.Exp.Neurol. 60, 1105-1119.
25. Johansson, C. B., Momma, S., Clarke, D. L., Risling, M., Lendahl, U., Frisen, J.
1999. Identification of a neural stem cell in the adult mammalian central nervous
system. Cell 96, 25-34.
26. Kiefer, M., Eymann, R., von, T. S., Muller, A., Steudel, W. I., Booz, K. H. 1998.
The ependyma in chronic hydrocephalus. Childs Nerv.Syst. 14, 263-270.
27. Klekamp, J. 2002. The pathophysiology of syringomyelia - historical overview
and current concept. Acta Neurochir.(Wien.) 144, 649-664.
28. Klekamp, J., Volkel, K., Bartels, C. J., Samii, M. 2001. Disturbances of
cerebrospinal fluid flow attributable to arachnoid scarring cause interstitial edema
of the cat spinal cord. Neurosurgery 48, 174-185.
29. Kojima, A., Tator, C. H. 2002. Intrathecal administration of epidermal growth
factor and fibroblast growth factor 2 promotes ependymal proliferation and
functional recovery after spinal cord injury in adult rats. J.Neurotrauma 19, 223-
238.
30. Krassioukov, A. V., Weaver, L. C. 1995. Episodic hypertension due to autonomic
dysreflexia in acute and chronic spinal cord-injured rats. Am.J.Physiol 268,
H2077-H2083.
31. Lederhaus, S. C., Pritz, M. B., Pribram, H. F. 1988. Septation in syringomyelia
and its possible clinical significance. Neurosurgery 22, 1064-1067.
32. Lee, G. Y., Jones, N. R., Mayrhofer, G., Brown, C., Cleland, L. 2005. Origin of
macrophages in a kaolin-induced model of rat syringomyelia: a study using
radiation bone marrow chimeras. Spine 30, 194-200.
33. Levine, D. N. 2004. The pathogenesis of syringomyelia associated with lesions at
the foramen magnum: a critical review of existing theories and proposal of a new
hypothesis. J.Neurol.Sci. 220, 3-21.
34. Loth, F., Yardimci, M. A., Alperin, N. 2001. Hydrodynamic modeling of
cerebrospinal fluid motion within the spinal cavity. J.Biomech.Eng 123, 71-79.
35. Martens, D. J., Seaberg, R. M., van der, K. D. 2002. In vivo infusions of
exogenous growth factors into the fourth ventricle of the adult mouse brain
increase the proliferation of neural progenitors around the fourth ventricle and the
central canal of the spinal cord. Eur.J.Neurosci. 16, 1045-1057.
36. Matthews, M. A., St Onge, M. F., Faciane, C. L. 1979. An electron microscopic
analysis of abnormal ependymal cell proliferation and envelopment of sprouting
axons following spinal cord transection in the rat. Acta Neuropathol.(Berl) 45, 27-
36.
37. Menick, B. J. 2001. Phase-contrast magnetic resonance imaging of cerebrospinal
fluid flow in the evaluation of patients with Chiari I malformation. Neurosurg
Focus 11, 1-4.
38. Milhorat, T. H., Nobandegani, F., Miller, J. I., Rao, C. 1993. Noncommunicating
syringomyelia following occlusion of central canal in rats. Experimental model
and histological findings. J.Neurosurg. 78, 274-279.
39. Miller, R. H., Ono, K. 1998. Morphological analysis of the early stages of
oligodendrocyte development in the vertebrate central nervous system.
Microsc.Res.Tech. 41, 441-453.
40. Mothe, A. J., Tator, C. H. 2005. Proliferation, migration, and differentiation of
endogenous ependymal region stem/progenitor cells following minimal spinal
cord injury in the adult rat. Neuroscience 131, 177-187.
41. Rossier, A. B., Foo, D., Shillito, J., Dyro, F. M. 1985. Posttraumatic cervical
syringomyelia. Incidence, clinical presentation, electrophysiological studies,
syrinx protein and results of conservative and operative treatment. Brain 108 ( Pt
2), 439-461.
42. Schwartz, E. D., Yezierski, R. P., Pattany, P. M., Quencer, R. M., Weaver, R. G.
1999. Diffusion-weighted MR imaging in a rat model of syringomyelia after
excitotoxic spinal cord injury. AJNR Am.J.Neuroradiol. 20, 1422-1428.
43. Stoodley, M. A., Brown, S. A., Brown, C. J., Jones, N. R. 1997. Arterial
pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in
the sheep spinal cord. J.Neurosurg. 86, 686-693.
44. Stoodley, M. A., Gutschmidt, B., Jones, N. R. 1999. Cerebrospinal fluid flow in
an animal model of noncommunicating syringomyelia. Neurosurgery 44, 1065-
1075.
45. Stoodley, M. A., Jones, N. R., Brown, C. J. 1996. Evidence for rapid fluid flow
from the subarachnoid space into the spinal cord central canal in the rat. Brain
Res. 707, 155-164.
46. Storer, K. P., Toh, J., Stoodley, M. A., Jones, N. R. 1998. The central canal of the
human spinal cord: a computerised 3-D study. J.Anat. 192 ( Pt 4), 565-572.
47. Takahashi, M., Arai, Y., Kurosawa, H., Sueyoshi, N., Shirai, S. 2003. Ependymal
cell reactions in spinal cord segments after compression injury in adult rat.
J.Neuropathol.Exp.Neurol. 62, 185-194.
48. Talbott, J. F., Loy, D. N., Liu, Y., Qiu, M. S., Bunge, M. B., Rao, M. S.,
Whittemore, S. R. 2005. Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor
cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of
astrocytes. Experimental Neurology 192, 11-24.
49. Vaquero, J., Ramiro, M. J., Oya, S., Cabezudo, J. M. 1981. Ependymal reaction
after experimental spinal cord injury. Acta Neurochir.(Wien.) 55, 295-302.
50. Weiss, S., Dunne, C., Hewson, J., Wohl, C., Wheatley, M., Peterson, A. C.,
Reynolds, B. A. 1996. Multipotent CNS stem cells are present in the adult
mammalian spinal cord and ventricular neuroaxis. J.Neurosci. 16, 7599-7609.
51. Yamamoto, S., Yamamoto, N., Kitamura, T., Nakamura, K., Nakafuku, M. 2001.
Proliferation of parenchymal neural progenitors in response to injury in the adult
rat spinal cord. Exp.Neurol. 172, 115-127.
52. Yang, L., Jones, N. R., Stoodley, M. A., Blumbergs, P. C., Brown, C. J. 2001.
Excitotoxic model of post-traumatic syringomyelia in the rat. Spine 26, 1842-
1849.
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