The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis

Zamboni, Paolo

doi:10.1258/jrsm.99.11.589

Cited by 190 publications

(175 citation statements)

References 26 publications

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“…In addition, the iron deposits represent a powerful chemotactic stimulus that attracts macrophages. This is confirmed by the presence of ironladen macrophages in the MS plaques, as shown in Figure 1 (Adams, 1988(Adams, , 1989Zamboni, 2006;Zamboni et al, 2008).…”

Section: Biological Links Of Iron Overload To Autoimmune Inflammationmentioning

confidence: 73%

“…In CVD, the chain is triggered by altered VHs with consequent disturbed microcirculation, bringing about erythrocyte extravasation as a primary source of iron stores (Bergan et al, 2006;Zamboni et al, 2006Zamboni et al, , 2008. We hypothesize that the same mechanism could also be responsible for iron deposition in CCSVI associated with MS (Zamboni, 2006;Zamboni et al, 2008). Histology confirms erythrocyte extravasation in brain plaques of MS just at the perivenular level (Adams, 1988(Adams, , 1989Zamboni, 2006).…”

Section: Peculiarity Of Anomalous Cerebral Venous Blood Flow In Multimentioning

confidence: 80%

“…We hypothesize that the same mechanism could also be responsible for iron deposition in CCSVI associated with MS (Zamboni, 2006;Zamboni et al, 2008). Histology confirms erythrocyte extravasation in brain plaques of MS just at the perivenular level (Adams, 1988(Adams, , 1989Zamboni, 2006). Figure 1 depicts a streak of blood encircling the venous wall in an MS plaque.…”

Section: Peculiarity Of Anomalous Cerebral Venous Blood Flow In Multimentioning

confidence: 80%

“…Figure 1 depicts a streak of blood encircling the venous wall in an MS plaque. The mechanisms involved in MS and CVD have many common features that exhibit intriguing similarities in the iron-mediated pathophysiology of the disease mechanisms (Zamboni, 2006). The recent description of altered VHs, together with immune cascade infiltration, systemic cellular pool extravasations, altered physiology of nephron metallobiology and classical theories explaining fibrin cuff and T-cell iron-laden macrophages indicate many similarities between MS and CVD, and are summarized in Table 2.…”

Section: Peculiarity Of Anomalous Cerebral Venous Blood Flow In Multimentioning

confidence: 99%

“…Iron stores are arranged in hemosiderin deposits as well as in ferritin-like structures inside the macrophage, curiously resembling perivenous iron stores commonly observed in peripheral venous disease. Starting from histology, it has been delineated an impressive parallel between the inflammatory process activated in the course of chronic venous disorders (CVDs) (Zamboni, 2006;Zamboni et al, 2008), and that profoundly studied in MS (Minagar et al, 2006;Frohman et al, 2006), although a parallel evidence of venous hemodynamic (VH) impairment in MS was still lacking (Zamboni, 2006). However, two important occurrences have taken place in the past 2 years: (1) a demonstration of altered venous flow in the cerebral venous system in the course of MS and (2) the development of advanced MRI techniques that have brought about an extraordinary improvement in the capacity to assess iron stores and cerebral veins.…”

mentioning

confidence: 99%

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Anomalous Venous Blood Flow and Iron Deposition in Multiple Sclerosis

Singh

Zamboni

2009

J Cereb Blood Flow Metab

180

155

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Multiple sclerosis (MS) is primarily an autoimmune disorder of unknown origin. This review focuses iron overload and oxidative stress as surrounding cause that leads to immunomodulation in chronic MS. Iron overload has been demonstrated in MS lesions, as a feature common with other neurodegenerative disorders. However, the recent description of chronic cerebrospinal venous insufficiency (CCSVI) associated to MS, with significant anomalies in cerebral venous outflow hemodynamics, permit to propose a parallel with chronic venous disorders (CVDs) in the mechanism of iron deposition. Abnormal cerebral venous reflux is peculiar to MS, and was not found in a miscellaneous of patients affected by other neurodegenerative disorders characterized by iron stores, such as Parkinson's, Alzheimer's, amyotrophic lateral sclerosis. Several recently published studies support the hypothesis that MS progresses along the venous vasculature. The peculiarity of CCSVI-related cerebral venous blood flow disturbances, together with the histology of the perivenous spaces and recent findings from advanced magnetic resonance imaging techniques, support the hypothesis that iron deposits in MS are a consequence of altered cerebral venous return and chronic insufficient venous drainage.

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Section: Biological Links Of Iron Overload To Autoimmune Inflammationmentioning

confidence: 73%