Endothelial cells, cerebral

Fig. 15.2 Diagram showing a transverse cross-section of a cerebral capillary. The endothelial cells, responsible for the main barrier properties of the blood-brain barrier are separated from the astrocyte foot processes, pericytes and occasional neurons by the basement membrane. All these components make up the blood-brain barrier.

El-Bacha RS, Minn A. Drug metabolizing enzymes in cerebrovascular endothelial cells afford a metabolic protection to the brain. Cell Mol Biol 1999 45 15-23 Minn A, Ghersi-Egea JF, Perrin R, Leininger B, Siest G. Drug metabolizing enzymes in the brain and cerebral microvessels. Brain Res Rew 1991 16 65-82. 

Later on, the importance of xanthine oxidase as the producer of reoxygenation injury was questioned at least in the cells with low or no xanthine oxidase activity. Thus, it has been shown that human and rabbit hearts, which possess extremely low xanthine oxidase activity, nonetheless, develop myocardial infractions and ischemia-reperfusion injury [9], However, recent studies supported the importance of the xanthine oxidase-catalyzed oxygen radical generation. It has been showed that xanthine oxidase is partly responsible for reoxygenation injury in bovine pulmonary artery endothelial cells [10], human umbilical vein and lymphoblastic leukemia cells [11], and cerebral endothelial cells [12], Zwang et al. [11] concluded that xanthine dehydrogenase may catalyze superoxide formation without conversion to xanthine oxidase using NADH instead of xanthine as a substrate. 

A2B receptors are found on endothelial cells, where they regulate vascular permeability, and on epithelial cells, where they regulate water secretion. These receptors are upregulated in the hippocampus following cerebral ischemic preconditioning and are thought to play a protective role. Both A2A and A2B receptors contribute to dilation of cerebral microvessels in response to adenosine. 

The blood-brain barrier is markedly different from peripheral capillaries Peripheral capillaries are fenestrated with openings up to 50 nm wide. In contrast, cerebral endothelial cells are closely connected by tight junctions and zonulae occludentes, resulting in extremely high transendothelial resistances of up to 1500-2000 12 cm2 [16] (Figure 17.1). The capillaries are surrounded by a basal membrane enclosing intermittently pericytes, which have been postulated to be involved in host defense. The outer surface of the basement membrane is covered by astrocytic foot processes. Most likely, secretion of soluble growth factors by astrocytes plays an important role in endothelial cell differentiation. 

The cerebral endothelial cells of the blood-brain barrier originate from the middle germinal sheet of the embryo, the mesoderm [17]. Concomitant with migration and proliferation of capillary endothelial cells during formation of the cerebral vascular network occurs the imprinting of the cells. Thereby, induction by the cellular surrounding plays an important role [18-21], The relevance of the cellular environment for the development of the barrier function of cerebral microvessels was first demonstrated by Stewart and Wiley [22], who transplanted embryonic brain tissue of a quail into embryonic gut tissue of chicken and vice versa. The cerebral transplant was vascularized by intestinal vessels, in which properties of the blood-brain barrier had been induced. In transplanted brain vessels, however, no characteristics of a barrier could be demonstrated, due to the lack of a neuronal environment. These results indicated that the cerebral microvessels are of extraneuronal origin, with properties that are induced by the cellular environment. In addition, brain tissue has the capability to induce blood-brain barrier characteristics also in noncerebral vascular tissue [23],... 

Monocultures form the base of most cerebral endothelial cell culture models [105-107], In the case of filter-grown cells, some authors recommend coculture with astrocytes or the use of astrocyte-conditioned media [108-110], The necessity of this approach is presently under discussion, as cells which had been cultured without supplementation with conditioned media show similar features [94, 111],... 

Considering the spatial geometry of cerebral capillaries and capillary blood flow, a number of dynamic models of the blood-brain barrier have been developed, in which endothelial cells are cultured inside a permeable tube, the outer surface of which is coated with astrocytes. Supply of the cells with nutrients and artificial blood flow are maintained by using a peristaltic pump system [112, 113]. 

Faso L, Trowbridge RS, Quan W, Yao XL, Jenkins EC, Maciulis A, Bunch TD, Wisniewski HM (1994) Characterization of a strain of cerebral endothelial cells... 

Xu, J., Yeh, C.H., Chen, S.W., Turning He, Sensi, S.L., Canzoniero, L.M.T., Choi, D.W., and Hsu., C.Y., 1998, Involvement of de novo ceramide biosynthesis in tumor necrosis factor-a cycloheximide-induced cerebral endothelial cell death. J. Biol. Chem. 273 16521-16526. 

MiravaUe, L., Tokuda, T., Chiarle, R., et al. (2000) Substitutions at codon 22 of Alzheimer s A-beta peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J. Biol. Chem., 275, 27110-27116. 

Endothelial cells of the cerebral capillaries are linked by tight junctions, sufficiently effective that there is no space between them. A well-developed basal lamina surrounds these capillaries and the external surface of the capillaries is almost entirely covered by processes of the astrocytes... 

Platelet aggregation increases like an avalanche because, once activated, platelets can activate other platelets. On the injured endothelial cell, a platelet thrombus is formed, which obstructs blood flow. Ultimately, the vascular lumen is occluded by the thrombus as the latter is solidified by a vasoconstriction produced by the release of serotonin and thromboxane A2 from the aggregated platelets. When these events occur in a larger coronary artery, the consequence is a myocardial infarction involvement of a cerebral artery leads to stroke. 

The BBB separates cerebral capillary blood from brain parenchymal tissue. The B B B is formed by endothelial cells lining the blood capillaries in the brain. Unlike the intestinal membrane, BBB has little UWL. The paracellular pathway is negligible for most compounds under physiological conditions. 

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