Microvascular barrier

In support of the antioxidant activity of resveratrol, a number of studies have demonstrated protective effects on oxidative cardiovascular injury." - In animal models, preinfusion of resveratrol prevents reperfusion-induced arrhythmias and mortality due to its antioxidant, free radical-scavenging activity as well as its ability to increase NO release. " These in vivo findings are supported by in vitro observations indicating that resveratrol significantly inhibits the ischemia/reperfusion-induced leukocyte recruitment and superoxide-related microvascular barrier dys-... 

Early studies indicate that combined GP Ilb/IIIa inhibition with rt-PA thrombolysis may improve clinical and MRI outcomes after acute ischemic stroke, with an acceptable safety prohle. The dual targeting of platelets and hbrin by combination therapy may provide synergistic benefits, including increased arterial recanalization, reduced microvascular thrombosis, reduced arterial reocclusion, and less rt-PA-mediated blood-brain barrier injury and secondary activation of the coagulation system. 

Balabanov R, Dore-Duffy P. Role of the CN S microvascular pericyte in the blood-brain barrier. J Neurosci Res 1998 53 637-644. 

Freshly isolated or subcultured brain microvascular endothelial cells offer a notable in vitro tool to study drug transport across the blood-brain barrier. Cells can be grown to monolayers on culture plates or permeable membrane supports. The cells retain the major characteristics of brain endothelial cells in vivo, such as the morphology, specific biochemical markers of the blood-brain barrier, and the intercellular tight junctional network. Examples of these markers are y-glutamyl transpeptidase, alkaline phosphatase, von-Willebrandt factor-related antigen, and ZO-1 tight junctional protein. The methods of... 

Figure 2.5. Setup for in vitro measurement of blood-brain barrier permeability with a co-culture of bovine brain microvascular endothelial cells (BBMEC) and an astro ioma cell line, C6. The BBMEC are grown on top of a filter insert. The C6 cells are either grown on the opposite side of the filter or on the bottom of the wells. Transport across the BBMEC monolayer is measured by adding the test substance to the upper chamber and sampling from the lower chamber. The tightness of the monolayer is also characterized by the transendothelial electrical resistance (TEER). Courtesy of T. Abbruscato.

Brain microvascular EC monolayers together with an astrocyte-enriched subendothelial collagen gel can be used to simulate the blood-brain barrier (BBB) (39). Such systems are invaluable to screen for compounds able to penetrate the BBB to access brain tumors or metastases. In addition, glioma cell invasion into brain fragments has enabled better understanding of the properties of these highly invasive tumors and identification of potential therapeutic targets (40). 

Related to the post-traumatic microvascular damage is the pathophysiological process of vasogenic brain edema that represents a disruption of blood-brain barrier integrity, resulting in sodium and protein accumulation and osmotic fluid expansion of the brain extracellular space. Clinically, this is reflected by an increase in intracranial pressure which, if unchecked, can cause secondary compressive injury to vital brain structures. 

Button TA, Mang HE, Campos SB, Sandoval RM, Yoder MC, Molitoris BA Injury ofthe renal microvascular endothelium alters barrier function after ischemia. American Journal of Physiology - Renal Fluid Electrolyte Physiology 285 F191-F198, 2003... 

Mackic JB, Stins M, McComb JG, Calero M, Ghiso J, et al. 1998. Human blood-brain barrier receptors for Alzheimer s amyloid-beta 1-40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer. J. Clin. Invest. 1024 734 13... 

ENDOTHELIAL AND MICROVASCULAR CHANGES 2.3.1 Breakdown of the Blood-Brain Barrier... 

Lossinsky, A. S., Vorbrodt, A. W., and Wisniewski, H. M., Scanning and transmission electron microscopic studies of microvascular pathology in the osmotically impaired blood-brain barrier, J. Neurocytol., 24, 795, 1995. 

Hermanns MI, Unger RE, Kehe K, et al. Lung epithelial cell lines in coculture with human microvascular endothelial cells development of an alveolo-capillary barrier in vitro. Lab Invest 2004 84 736-752. 

Joo F. Brain microvascular cyclic nucleotides and protein phosphorylation. In Pardridge WM, ed. Blood Brain Barrier Cellular and Molecular Biology. Raven. New York, 1993, pp. 267-287. 

Connective tissue, which consists primarily of fibroblasts, produces extracellular matrix materials that surround cells and tissues, determining their appropriate position within the organ (see Chapter 49). These materials include structural proteins (collagen and elastin), adhesive proteins (fibronectin), and glycosaminoglycans (heparan sulfate, chondroitin sulfate). The unique structures of the proteins and carbohydrates found within the extracellular matrix allow tissues and organs to carry out their many functions. A loss of these supportive and barrier functions of connective tissue sometimes leads to significant clinical consequences, such as those that result from the microvascular alterations that lead to blindness or renal failure, or peripheral neuropathies in patients with diabetes mellitus. 

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