Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency
Maha M.A. Zakaria1, Shahira Y. Mikhael1, Azza K. Abu Hussein1, Rania A. Salah El-din1, Hany W. Abd El-Malak1, Iman H. Hewedi2, Hany S. Nadim1; Abdel Malak, Hany;
Abstract
Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the cerebrospinal venous
outflow routes, which is postulated to cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to
iron deposition which triggers inflammation and demyelination in MS. Invasive endovascular treatment of CCSVI
was initiated based on the previous theory. The present study was designed to validate this hypothesis using a rat
model of CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats (n = 15), and sham-operated
rats (n = 15) were used as a control group. The rats were followed clinically for eight months and neurological
examination detected no weakness or paralysis in the operated rats. At the end of the experiment, the rats were
sacrificed and the brains were processed for histopathological examination of tissue sections stained by hematoxylin
and eosin, myelin stain, silver impregnation, iron stain and immunohistochemical preparations for GFAP, CD68 and
CD45. Semithin sections stained with toluidine blue were also examined. In the JVL group, increased iron deposition
in the white matter was detected. An increase in the size and number of astrocytes along with increased GFAP
immunoreactivity denoting reactive gliosis was also noted in the JVL group. However, no signs of demyelination,
inflammation or axonopathy were detected. This study revealed that iron deposition in the JVL group as a model
for CCSVI was not associated with cardinal histopathological findings of MS. It is therefore recommended that the
invasive endovascular treatment of CCSVI should be reconsidered and further controlled clinical studies be carried
out to provide a better understanding of the pathogeneses of MS.
outflow routes, which is postulated to cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to
iron deposition which triggers inflammation and demyelination in MS. Invasive endovascular treatment of CCSVI
was initiated based on the previous theory. The present study was designed to validate this hypothesis using a rat
model of CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats (n = 15), and sham-operated
rats (n = 15) were used as a control group. The rats were followed clinically for eight months and neurological
examination detected no weakness or paralysis in the operated rats. At the end of the experiment, the rats were
sacrificed and the brains were processed for histopathological examination of tissue sections stained by hematoxylin
and eosin, myelin stain, silver impregnation, iron stain and immunohistochemical preparations for GFAP, CD68 and
CD45. Semithin sections stained with toluidine blue were also examined. In the JVL group, increased iron deposition
in the white matter was detected. An increase in the size and number of astrocytes along with increased GFAP
immunoreactivity denoting reactive gliosis was also noted in the JVL group. However, no signs of demyelination,
inflammation or axonopathy were detected. This study revealed that iron deposition in the JVL group as a model
for CCSVI was not associated with cardinal histopathological findings of MS. It is therefore recommended that the
invasive endovascular treatment of CCSVI should be reconsidered and further controlled clinical studies be carried
out to provide a better understanding of the pathogeneses of MS.
Other data
Title | Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency | Other Titles | Failure of the vascular hypothesis of multiple sclerosis in rat model of CCSVI | Authors | Maha M.A. Zakaria1, Shahira Y. Mikhael1, Azza K. Abu Hussein1, Rania A. Salah El-din1, Hany W. Abd El-Malak1, Iman H. Hewedi2, Hany S. Nadim1 ; Abdel Malak, Hany | Keywords | CCSVI, multiple sclerosis, animal model, jugular veins, iron overload | Issue Date | Jan-2017 | Journal | Folia Neuropathologuca, 2017; 55 (1): 49-59 | DOI | https://doi.org/10.5114/fn.2017.66713 |
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