Abstract
BackgroundThe brain endothelium is a key component of the blood brain barrier which is compromised following ischemia, allowing infiltration of damaging immune cells and other inflammatory molecules into the brain. Intravenous immunoglobulin (IVIg) is known to reduce infarct size in a mouse model of experimental stroke.FindingsFlow cytometry analysis showed that the protective effect of IVIg in ischemia and reperfusion injury in vivo is associated with reduced leukocyte infiltration, suggesting an involvement of the endothelium. In an in vitro model of ischemia, permeability analysis of the mouse brain endothelial cell line bEnd.3 revealed that IVIg prevented the loss of permeability caused by oxygen and glucose deprivation (OGD). In addition, western blot analysis of these brain endothelial cells showed that IVIg prevented the down-regulation of tight junction proteins claudin 5 and occludin and the decline in anti-apoptotic proteins Bcl-2 and Bcl-XL caused by OGD.ConclusionIVIg protects endothelial cells from ischemic insult. These studies support the use of IVIg as a pharmacological intervention for stroke therapy.
Highlights
Intravenous immunoglobulin (IVIg) is a purified concentrated human immunoglobulin solution composed primarily of IgG, obtained by fractionating blood plasma from a pool of healthy donors
The findings of this study reveal a beneficial effect by IVIg on ischemia-induced leukocyte recruitment as well as on endothelial permeability, as well as an anti-apoptotic effect on endothelial cells mediated by B-cell lymphoma 2 (Bcl-2) and Bcl-XL
Since tight regulation of endothelial permeability is pivotal to blood brain barrier (BBB) integrity, we assessed the effect of IVIg on permeability using the mouse brain endothelial cell line bEnd.3, measured as the ability for FITC-dextran to cross the cell monolayer 3 h after oxygen and glucose deprivation (OGD)
Summary
Intravenous immunoglobulin (IVIg) is a purified concentrated human immunoglobulin solution composed primarily of IgG, obtained by fractionating blood plasma from a pool of healthy donors. Animal studies have shown that administration of IVIg impairs leukocyte adhesion to endothelial cells, attenuates complement-mediated damage, modulates cytokine production by various cell types and inhibits apoptosis [2,6-8]. It is not known whether IVIg protects from cerebrovascular dysfunction following ischemic stroke. Measuring tight junction proteins has been shown as a valid indicator of the paracellular pathway of endothelial permeability and its damage in ischemic injury [9]. The findings of this study reveal a beneficial effect by IVIg on ischemia-induced leukocyte recruitment as well as on endothelial permeability (mediated by tight-junction proteins claudin 5 and occludin), as well as an anti-apoptotic effect on endothelial cells mediated by Bcl-2 and Bcl-XL. Intravenous immunoglobulin (IVIg) is known to reduce infarct size in a mouse model of experimental stroke
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
