Clostridium perfringens Prototoxin-Induced Alteration of Endothelial Barrier Antigen (EBA) Immunoreactivity at the Blood–Brain Barrier (BBB)

Zhu, Chunni; Ghabriel, M. N.; Blumbergs, Peter; Reilly, Peter; Manavis, Jim; Youssef, J; Hatami, S; Finnie, John

doi:10.1006/exnr.2001.7652

Cited by 56 publications

(46 citation statements)

References 29 publications

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“…8 D-I ), which is in agreement with previous findings of sparse EBA-negative vessels in normal animals (Nishigaya et al, 2000;Zhu et al, 2001). In contrast, dyskinetic animals displayed a visible reduction of EBA expression in several areas.…”

Section: The Bbb Is Defective In Dyskinetic Animalssupporting

confidence: 91%

“…Weak or absent EBA staining is considered as a marker of BBB disruption (Sternberger et al, 1989;Nishigaya et al, 2000;Zhu et al, 2001). Studies addressing the time course of EBA expression after brain injury have shown that its downregulation precedes neovessel formation and that reexpression of the EBA antigen occurs within a narrow time window (Rosenstein et al, 1992;Nishigaya et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical detection of serum albumin in the brain parenchyma is an established method to evaluate the cumulative effect of BBB disruption during a certain period of time (Nag, 1996a,b). A reduced EBA expression on blood vessel walls has been associated with a mild opening of the BBB to albumin (Zhu et al, 2001). .…”

Section: Discussionmentioning

confidence: 99%

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Endothelial Proliferation and Increased Blood–Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydroxyphenyl-l-Alanine-Induced Dyskinesia

Westin

Lindgren²,

Gardi³

et al. 2006

J. Neurosci.

115

132

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3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia is associated with molecular and synaptic plasticity in the basal ganglia, but the occurrence of structural remodeling through cell genesis has not been explored. In this study, rats with 6-hydroxydopamine lesions received injections of the thymidine analog 5-bromo-2Ј-deoxyuridine (BrdU) concomitantly with L-DOPA for 2 weeks. A large number of BrdU-positive cells were found in the striatum and its output structures (globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata) in L-DOPA-treated rats that had developed dyskinesia. The vast majority (60 -80%) of the newborn cells stained positively for endothelial markers. This endothelial proliferation was associated with an upregulation of immature endothelial markers (nestin) and a downregulation of endothelial barrier antigen on blood vessel walls. In addition, dyskinetic rats exhibited a significant increase in total blood vessel length and a visible extravasation of serum albumin in the two structures in which endothelial proliferation was most pronounced (substantia nigra pars reticulata and entopeduncular nucleus). The present study provides the first evidence of angiogenesis and blood-brain barrier dysfunction in an experimental model of L-DOPA-induced dyskinesia. These microvascular changes are likely to affect the kinetics of L-DOPA entry into the brain, favoring the occurrence of motor complications.

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Section: The Bbb Is Defective In Dyskinetic Animalssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Endothelial Proliferation and Increased Blood–Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydroxyphenyl-l-Alanine-Induced Dyskinesia

Westin

Lindgren²,

Gardi³

et al. 2006

J. Neurosci.

115

132

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“…Endothelial barrier antigen (EBA), recognized by SMI-71 monoclonal antibodies (Sternberger Inc.), is a specific marker of the cerebral capillary barrier endothelium [7,15]. The expression of EBA is in high correlation with functional integrity of the blood-brain barrier (BBB) and is disordered in diseases associated with BBB impairment [9,11,16,22].…”

mentioning

confidence: 99%

Modeling and immunohistochemical analysis of C6 glioma In Vivo

et al. 2007

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A reproducible in vivo model of C6 glioma was developed in Wistar rats. Analysis of histological preparations showed similar morphology of rat C6 glioma and human glioblastoma. The formation of a glial border at the periphery of the glioma, consisting of GFAP-positive reactive astrocytes, was shown by the immunohistochemical method. The border appeared on day 8 after implantation, astrogliosis was observed until animal death (day 28). Reactive astrocytes with branched processes surrounded not only the primary glioma focus, but also all sites of tumor invasion in the nervous tissue. Expression of EBA (blood-brain barrier marker) was disturbed and synthesis of AMVB1 (endothelial antigen) increased in neoplastic endotheliocytes, which suggested pronounced functional restructuring of the blood-tumor barrier in comparison with the blood-brain barrier. The phenomenon of predominant expression of GFAP and AMVB in the tumor tissue can be used for the development of systems for targeted drug transport into the tumor by means of appropriate antibodies.

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“…This toxin accumulates mainly in the brain and kidneys when intravenously injected into rats (14), causing injury to neuronal cells (15)(16)(17) and cerebral blood vessels (18). One characteristic feature of the toxin is its extraordinarily high potency; 20 ng of ET kills a mouse within 1 h. 2 We have previously shown that proteolytic activation of ⑀-protoxin (ProET) is due to the removal of a C-terminal peptide (19,20) and that activated ET forms a heptamer in rat synaptosomal membranes (20).…”

mentioning

confidence: 99%

Clostridium perfringens ε-Toxin Forms a Heptameric Pore within the Detergent-insoluble Microdomains of Madin-Darby Canine Kidney Cells and Rat Synaptosomes

Miyata

Minami

Tamai

et al. 2002

Journal of Biological Chemistry

129

138

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Clostridium perfringens ⑀-toxin, which is responsible for enterotoxaemia in ungulates, forms a heptamer in rat synaptosomal and Madin-Darby canine kidney (MDCK) cell membranes, leading to membrane permealization. Thus, the toxin may target the detergent-resistant membrane domains (DRMs) of these membranes, in analogy to aerolysin, a heptameric pore-forming toxin that associates with DRMs. To test this idea, we examined the distribution of radiolabeled ⑀-toxin in DRM and detergent-soluble membrane fractions of MDCK cells and rat synaptosomal membranes. When MDCK cells and synaptosomal membranes were incubated with the toxin and then fractionated by cold Triton X-100 extraction and flotation on sucrose gradients, the heptameric toxin was detected almost exclusively in DRMs. The results of a toxin overlay assay revealed that the toxin preferentially bound to and heptamerized in the isolated DRMs. Furthermore, cholesterol depletion by methyl-␤-cyclodextrin abrogated their association and lowered the cytotoxicity of the toxin toward MDCK cells. When ⑀-protoxin, an inactive precursor able to bind to but unable to heptamerize in the membrane, was incubated with MDCK cell membranes, it was detected mainly in their DRMs. These results suggest that the toxin is concentrated and induced to heptamerize on binding to a putative receptor located preferentially in DRMs, with all steps from initial binding through pore formation completed within the same DRMs.

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Clostridium perfringens Prototoxin-Induced Alteration of Endothelial Barrier Antigen (EBA) Immunoreactivity at the Blood–Brain Barrier (BBB)

Cited by 56 publications

References 29 publications

Endothelial Proliferation and Increased Blood–Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydroxyphenyl-l-Alanine-Induced Dyskinesia

Endothelial Proliferation and Increased Blood–Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydroxyphenyl-l-Alanine-Induced Dyskinesia

Modeling and immunohistochemical analysis of C6 glioma In Vivo

Clostridium perfringens ε-Toxin Forms a Heptameric Pore within the Detergent-insoluble Microdomains of Madin-Darby Canine Kidney Cells and Rat Synaptosomes

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