Blood capillaries brain

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. 

The entry of toxins into the brain and central nervous system (CNS) is frequently more difficnlt than into other tissues. The function of this blood-brain barrier is related to impaired permeability of the blood capillaries in brain tissne, the necessity for toxins to penetrate glial cells, and the low protein content of the CNS interstitial flnid (Klaassen, 1986). Lipid solnbihty of a toxin is an important factor in the penetration of the blood-brain barrier. 

All inhaled anaesthetic drugs must be soluble in blood and brain in order to pass across the alveolar-capillary membrane and the blood-brain barrier. The term used to quantify solubility is partition coefficient. For anaesthetic purposes this is defined as the ratio of the concentration of dissolved gas/vapour in the blood to the concentration in the alveoli at... 

Tight junctions between endothelial cells of blood capillaries in the brain prevent free diffusion of compounds from the blood stream into brain cells and form the blood-brain barrier.140 Tight junctions between neurons and adjacent cells surround the nodes of Ranvier (Chapter 30). 

Blood capillaries in the brain are structurally different from the blood capillaries in other tissues these structural differences result in a permeability barrier between the blood within brain capillaries and the extracellular fluid in brain tissue. This permeability barrier, comprising the brain capillary endothelium, is known as the Blood-Brain Barrier (BBB). 

The brain capillary endothelium comprises the lumenal and ablumenal membranes of capillaries, which are separated by approximately 300 ran of endothelial cytoplasm (Figure 13.2). The structural differences between brain capillary endothelium and non-brain capillary endothelium are associated with the endothelial tight junctions. The non-brain capillaries have fenestrations (openings) between the endothelial cells through which solutes can move readily via passive diffusion. In brain capillaries, the endothelium has epithelial-like tight junctions which preclude movement via paracellular diffusion pathways. There is also minimal pinocytosis across brain capillary endothelim, which further limits transport of moieties from blood to brain. 

Consider two examples. First, in the brain capillary endothelium, luminal expression of the ATP-driven drug efflux pump, p-glycoprotein, provides a formidable barrier to drug penetration from blood to brain (Figure 15.2). This is best seen in... 

FiCURE 105-2. Schematic representation of a blood-cerebrospinal fluid barrier capillary, brain tissue capillary, and normal tissue capillary below). 

DOPA decarboxylase, a pyridoxal phosphate-requiring enzyme, catalyzes the synthesis of dopamine from DOPA. Dopamine is produced in neurons found in certain structures in the brain. It is believed to exert an inhibitory action within the central nervous system. Deficiency in dopamine production has been found to be associated with Parkinson s disease, a serious degenerative neurological disorder (Special Interest Box 14.3). The precursor l-DOPA is used to alleviate the symptoms of Parkinson s disease because dopamine cannot penetrate the blood-brain barrier. (The blood-brain barrier protects the brain from toxic substances. Many polar molecules and ions cannot move from blood capillaries, although most lipid-soluble substances readily pass across. The blood-brain barrier consists of connective tissue and specialized cells called astrocytes that envelop the capillaries.) Once l-DOPA is transported into appropriate nerve cells, it is converted to dopamine. 

The mechanism of fever induction has been studied most extensively. The brain is protected from the potentially harmful effects of biologically active substances or cells in the circulation by the blood-brain barrier, which is manifested by the extremely tight junctions between the endothelial cells lining blood capillaries,48 which prevent circulating substances of a particular size and chemical property (as well as cells) from entering the brain. Proinflammatory cytokines are of a sufficiently large size that makes it unlikely that they can pass the blood-brain barrier. However, numerous pathways to explain how cytokines produced in the periphery can influence central nervous system events have been studied. For example, highly localized... 

Capillaries in the Brain (the Blood-Brain Barrier). Capillaries in the brain are less permeable than capillaries in other tissues. This limited permeability, which is frequently called the blood-brain barrier, is essential for brain function. Reduced permeation provides a buffer that maintains a constant brain extracellular environment, even at times when blood chemistry is changing. The basis for this lower permeability is the relative paucity of pores in the brain endothelium. Therefore, molecules that move from blood to brain must diffuse through the endothelial cell membranes. As expected from this observation, the permeability of brain capillaries depends on the size and lipid solubility of the solute. In general, molecules that are larger than several hundred in molecular weight do not permeate into the brain. Empirical relationships between cerebrovascular permeability and the oil / water partition coefficient have been developed [26] (see Figure 5.27) ... 

---