Cerebral capillary

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.

Frank RN, Dutas S, Mancini MA. Pericyte coverage is greater in the retinal than in the cerebral capillaries of the rat. Invest Ophtalmol Visual Sci 1987 28 1089-1091. 

Kirsch T, Wellner M, Luft FC, Haller H, Li ppoldt A. Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats. Brain Res 2001 910 106-115. 

The density of cerebral capillaries, especially in the cortical grey matter, is very high with mean distances of 40 /xm. The capillary network has a total length of 600-650 km, the mean velocity of the blood flow is below 0.1 cm/s, and the luminal surface extends to 15-30 m2. Thus the blood-brain barrier represents an important surface for potential drug delivery besides gut (30CM100 m2), lung (70-120 m2), or skin (1.8 m2) [24-26, 33-37],... 

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]. 

Certain factors determine distribution of drugs to the central nervous system. An important determinant is the drug s molecular size, because cerebral capillaries have tight junctions and only the smallest molecules can pass through unless there is a specific carrier mechanism. However, drugs that are highly lipid soluble may pass through the brain s perme-... 

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... 

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. 

Tire brain, which must function in a chemically stable environment, is protected by a tough outer covering, the arachnoid membrane, and by the blood-brain barrier406 407 and the blood-cerebrospinal barrier. Both of these barriers consist of tight junctions similar to those seen in Fig. 1-15A. They are formed between the endothelial cells of the cerebral capillaries and between the epithelial cells that surround the capillaries of the choroid plexus. The choroid plexus consists of capillary beds around portions... 

Preston et al. [66] have shown that BBB permeability to the nonmetabolizable, but slowly BBB penetrant, tracer mannitol (182 Da), is between 0.19 and 0.22 pL/g/min in the brain of rats of 1 week of age and this permeability is identical to that of adult rats. The vascular space occupied by the tracer mannitol (the initial volume of distribution Fj) falls from 1.23 mL, at 1 week of age, to 0.75 mL per 100 g brain in the adult rat [66], indicating either a larger vascular volume, resulting from a greater capillary density or capillary diameter in the neonatal rat, or to a significant degree of internalization of the mannitol by the endothelium, possibly by fluid-phase endocytosis into the cerebral capillary endothelial cells in the newborn, compared to the adult. 

Blood-brain barrier The specialized anatomic arrangement of cerebral capillary walls that serves to restrict the passage of some drugs into the brain. 

Drewes LD, Lidinsky WA. Studies of cerebral capillary endothelial membrane. Adv Exp Med Biol 1980 131 17-27. 

Lechardeur D, Scherman D. Functional expression of the P-glycoprotein mdr in primary cultures of bovine cerebral capillary endothelial cells. Cell Biol Toxicol 1995 11(5) 283—293. 

The distribution of drugs depends on both the physicochemical properties of the drug molecules and the composition of tissue membranes. These factors can either result in a uniform or uneven distribution of dmgs into the various body compartments and fluids. In the extreme, distribution may tend toward an accumulation of drugs in particular tissues or to an almost complete exclusion of the drag from a particular compartment in a defined length of time. One unique compartment that has to be considered in this respect is the brain, which is separated from the capillary system of the blood by the blood-brain barrier, whose membrane has a special structure. It consists of a cerebral capillary network formed by a capillary endothelium that consists of a cell layer with continuous compact intercellular junctions. It has no pores, but special cells, astrocytes, which support the stability of the tissues, are situated at the bases of the endothelial membrane separating the brain and CSF from the blood. The astrocytes form an envelope around the capillaries. 

The permeability coefficient, P (cm/s), is defined by the following operational equation for non-directed flux from the blood to the brain across the cerebral capillaries. It can be determined by measuring the concentration of a drug in the plasma and brain as a function of time [56, 59] ... 

Blood-brain barrier The combination of tight endothelial junctions in cerebral capillaries together with their covering of astrocytes. 

Harik, N., S.I. Harik, N.T. Kuo, K. Sakai, R.J. Przybylski, and J.C. La Manna (1996). Time-course and reversibility of the hypoxia induced alterations in cerebral vascularity and cerebral capillary glucose transporter density. Brain Res. 737 335-338. 

The passage of substances across the blood-brain barrier (BBB) is regulated in the cerebral capillaries, which possess certain distinct different morphological and enzymatic properties compared with the capillaries of other organs. To provide an in vitro system with the functional characteristics of a BBB Cecchelli et al. (1999) developed an in vitro system with cloned bovine brain capillary endothelial cells on one side of a filter and rat astrocytes on the other side. 

Ehrlich (1) and Goldman (2) were the hrst to observe the existence of the blood-brain barrier (BBB) after the inj ection of the hydrophilic compound trypan blue in a rat did not distribute into and out of the brain. It is now known that the cerebral capillary regulates the influx and efflux of biologically important molecules both by preventing passive hydrophilic diffusion and by providing transport processes whose activity can be regulated in accordance with the metabolic and homeostatic requirements of the brain. 

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