Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency
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. I...
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Published in | Folia neuropathologica Vol. 55; no. 1; pp. 49 - 59 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Poland
Termedia Publishing House
01.01.2017
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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. |
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AbstractList | 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. |
Author | Zakaria, Maha M A Hewedi, Iman H El-Malak, Hany W Abd Nadim, Hany S Hussein, Azza K Abu El-Din, Rania A Salah Mikhael, Shahira Y |
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SubjectTerms | animal model Animals Brain - blood supply CCSVI Female iron overload jugular veins multiple sclerosis Multiple Sclerosis - etiology Random Allocation Rats Rats, Wistar Spinal Cord - blood supply Venous Insufficiency - complications |
Title | Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency |
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