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    Home > Biochemistry News > Biotechnology News > Blood-brain barrier.

    Blood-brain barrier.

    • Last Update: 2020-10-19
    • Source: Internet
    • Author: User
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    name
    it was discovered about a hundred years ago that animals were injected with
    active dye
    , and that
    tissues
    all over the body were stained but not by brain tissue. But if the dye is injected directly into the cobweb cavity, the brain tissue is quickly dyed. A number of experimental studies have shown that some substances do not enter the inter-brain tissue fluid at all from the blood;
    in short, there is a selective barrier between the blood-brain that prevents certain substances from being present by the "barrier" of the blood brain, known as the blood-brain barrier (BBB). The function of the blood-brain barrier is to ensure a high degree of stability of the brain's internal environment, which is good for the functioning of the central nervous system, and also to prevent the invasion of foreign bodies (
    microorganisms
    , toxins, etc.) and has a protective effect.I. The structural characteristics of the blood-brain barrier the material basis of the blood-brain barrier is the capillaries of the brain, which, unlike capillaries in other tissues, have the following three characteristics: (1) cerebral capillaries endoblast cells "weld" each other very closely, not as large as other tissue capillaries walls;
    (2) the substrate membrane outside capillary endoblast cells is continuous;
    (3) 85% of the outer area of capillaries is wrapped around the end of the glial cells. It can be seen that the substance from the blood into the brain tissue fluid to pass through more layers, including lipid (mass membrane) and non-lipid (base membrane) membrane structure. Among them, passing through capillary endoblast cells is a critical step. Compared with capillary endoskin cells in other tissues, such as muscle tissue, the cellular function of capillary endoskin cells in the cerebrovascular is weak.
    refore, for cerebral capillary endocute cells, the ability to transport substances (large molecules and electrolytes) by the action of cell drinking is very limited, which strengthens the barrier function of the cerebrovascular wall., the way matter passes through the blood-brain barriersubstances can be transferred from the blood to the brain tissue by diffusion or vector transport, from the brain tissue into the blood.the most important substances that pass through the blood-brain barrier by diffusion are water and gas. Traces of intravenous injection of heavy water (D2O) showed that the half-life of water molecule exchange in the brain was 12-25 seconds. Water can move freely into and out of brain tissue based on changes in plasma penetration pressure. Clinically, the use of intravenous injection of glycol and other substances, improve plasma penetration pressure, can make the brain dehydrated to reduce intracranial pressure, O2, CO2, N2O and other gases and volatile anesthetics can also spread rapidly into brain tissue. Fat-soluble substances and lipid solvents are easily passed through the lipid-pro-lipid membrane and can therefore spread rapidly into the brain, with ethanol the fastest known substance.glucose,
    amino acids
    and various ions are transported by carrier. Because of the stereospecificity of glucose carrier transport systems, only D-glucose enters the brain, while L-type ones do not. The speed of entry of various amino acids into brain tissue is different, which is related to the amount and quality (specificity) of amino acid carriers and carriers.
    is striking is that most of the amino acids that are nutritionally essential are rapidly transferred, and that it is non-essential amino acids that are difficult to cross the blood-brain barrier. The transport of various ions is also different, but is much slower than getting in and out of other tissues. Once the substances that can be diffused into the brain are dissophed to form ions, the speed of crossing the blood-brain barrier slows down, such as NH3, salbonate (unresolved), CO2 is faster than NH4, salbonate root, HCO3-entering brain tissue.
    of H-plus is also slow, in sharp contrast to the rapid spread of CO2. It is important to note that this characteristic is important for understanding the insodaency between blood pH and brain tissue pH, i.e. Pco2 in blood is more reflective of
    acid and alkali
    pH in blood pH. Caution is exercised when correcting diabetic acidosis with alkaline drugs (NaHCO3), as CO2 spreads faster than HCO3-enters brain tissue, which may further reduce pH in brain tissue.Iii, the impact factors the difficulty of material through the blood-brain barrier depends on two factors: one is the nature and state of the substance itself;(a) the pro-fat and hydrophoticcell membrane is a lipid-based bi-molecular layer structure, so any fat-pro-fat substance is easy to pass through the cell membrane; The pro-fat and hydrophobic properties of the substance depend on the chemical structure of the substance: those with polar groups are hydrophobic, while those with hydrophobic groups are less polar and more pro-fat. That is, there is a negative correlation between the polarity of the substance and the pro-fatness. Applying this principle in pharmaceutical science can chemically modify certain drugs that act on the central nervous system, reduce their polarity, enhance their hydropathy, and enable them to pass through the blood-brain barrier more quickly, thus improving the efficacy of the drug. For example, the transformation of barbito into phenytosis improves the effectiveness of hypnotic drugs.(ii) binding to plasma proteinin the capillaries of general tissue, hydromassive substances mostly enter the tissue through the gap between endothyl cells and across the substrate membrane (permeability, permeability). However, as mentioned earlier, cerebral capillary endothial cells are very closely "welded" and less permeable, and experiments have shown that substances with a molecular weight greater than 2,000 cannot be passed by endoth endoblast joints. Therefore, the substances that bind to plasma protein are difficult to pass through the blood-brain barrier, and in fact many substances in the plasma (
    hormones
    , fatty acids, bilirubin, etc.) are transported in combination with plasma proteins, because the binding of substances and plasma proteins is reversible, so the dynamic balance of binding and dissosis directly affects the speed at which substances pass through the blood-brain barrier. For example, in infants with high bilirubinemia (see Liver
    Biogenic
    ), bilirubin in the blood binds to plasma proteins to prevent bilirubin from entering brain tissue to cause damage. But if you give sulfonamide at this time. Because the latter can compete with bilirubin and plasma protein binding, so that a large number of free bilirubin (lipid-pro-fat) quickly through the blood-brain barrier, can cause serious consequences.(iii) Carrier transport system There are a variety of carrier proteins on the endoblast membrane of cerebrovascular endocrine, which can promote the transport of polar molecules that would otherwise be difficult to pass through the blood-brain barrier. The confirmed carrier systems are: (1) sugar carriers, (2) neutral amino acid carriers, (3) alkaline amino acid carriers, (4) short-chain monocrystic acid carriers, etc. glucose carrier has strong specificity as described above. In addition, sugar can also enter brain tissue more quickly, semi-lactose, while fructose is difficult to pass through the blood-brain barrier. Because of the lack of acidic amino acid carriers, glutamate and tianmen dongine are difficult to pass through the blood-brain barrier. Essential amino acids, especially aromatic and branch chains, are most likely to pass through the blood-brain barrier, and methionine passes more quickly. Although there are many amino acids that can pass through the blood-brain barrier, there are only a few amino acid vectors found, so at least some amino acid vectors are not very specific, so there may be competition. For example, in children with congenital phenylketonuria (phenylketonuria, PKU), the concentration of phenylalanine in the blood is too high, affecting tryptophan into brain tissue, resulting in brain dysplis in children. (iv) Bio-transformation Certain substances will be destroyed by the action of the cytosine endoenzyme system when passing through cerebrovascular endoblast cells, so even substances that can enter capillary endoblast cells may not necessarily be able to enter the brain through the blood-brain barrier. Cerebral capillary endoskine cells have been found to contain monoamine oxidase (MAO) to oxidize and break down neurotransmitters belonging to monoamines (e.g. cerium phenolamine, 5-serotonin, etc., see later), and γ-aminobutyric acid (GABA) Although it can be ingested by cerebral capillary endothyl cells, it is also destroyed by the role of GABA
    traminase
    in cells, if the enzyme is inhibited with β-aminoacetic acid, GABA can enter brain tissue. This bio-transformation in the cerebrovascular wall enhances the shielding of the blood-brain barrier and protects the inner environment of brain tissue from sudden changes in chemical composition in the blood. (v) the effect of the blood-brain barrier of newborns is not fully developed and the permeability is high. The rapidly growing brain tissue has a significant increase in the intake of certain substances that are actively metabolized, perhaps due to the accelerated transport itself or to the high conversion rate of metabolites. , there are differences in the blood-brain barrier in different areas of the brain. Pathological conditions, such as angioedema, brain tumors, and ionizing radiation damage, can increase the permeability of the blood-brain barrier.
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