High blood-brain barrier permeability

Introduction Central nervous system diseases often cause dramatic changes in the structure and function of the blood-brain barrier. The permeability of the barrier is significantly increased so that macromolecular substances such as plasma albumin can pass through the barrier. Severe brain damage leads to severe damage to the blood-brain barrier, allowing serum proteins to enter the brain tissue through the barrier. Neonatal nuclear jaundice and vascular cerebral edema make the tight junction between brain capillary endothelial cells open, and the permeability of the barrier is significantly increased, so that macromolecular substances such as plasma albumin (molecular weight of 69,000) can pass through the barrier.

Cause

The cause of high blood-brain barrier permeability

Neonatal nuclear jaundice and vascular cerebral edema make the tight junction between brain capillary endothelial cells open, and the permeability of the barrier is significantly increased, so that macromolecular substances such as plasma albumin (molecular weight of 69,000) can pass through the barrier. Severe brain damage leads to severe damage to the blood-brain barrier, allowing serum proteins to enter the brain tissue through the barrier. With the repair of the damage, the macromolecular substances first stop in the brain. After the complete recovery, the phenomenon of accelerated exchange of small molecules will disappear, and the blood-brain barrier function is normal. Ionizing radiation, laser and ultrasound can increase the permeability of the blood-brain barrier.

an examination

Related inspection

Electroencephalography CT examination

High blood-brain barrier permeability test

Under normal circumstances, the central transmitter can hardly pass the blood-brain barrier, which is conducive to maintaining the stability of the central transmitter level in the brain and eliminating the interference of extra-brain stimulation factors. Therefore, it may be related to the enzyme system in brain capillary endothelial cells. It has been found to contain monoamine oxidase, and various central transmitters are monoamines, such as catecholamines, serotonin, histamine, etc., which can be eliminated by monoamine oxidase. Live, this biochemical transformation in the cytoplasm of endothelial cells strengthens the function of the blood-brain barrier, which can stabilize the environment inside the brain tissue, and is less affected by the dramatic changes in the content of substances with strong physiological effects in the circulating blood.

1 using a smaller molecular weight horseradish peroxidase (a protein, molecular weight of about 40,000, molecular diameter of about 500 ~ 600 nm) or a fragment thereof as a marker for permeability of the capillary wall, a small molecular weight horseradish peroxidase fragment It can quickly enter the muscle tissue through the capillaries of the muscle, but this enzyme fragment in the brain capillaries is blocked in the blood vessels and cannot enter the brain tissue. In this barrier action, the basement membrane and the perivascular foot intermittent membrane only play a supporting role.

2 The pinocytosis of brain capillary endothelial cells is weak. Therefore, there is little material exchange between vascular endothelial cells and brain tissue. After ionizing radiation, the animals increased their vesicles and the permeability of the blood-brain barrier increased.

Differential diagnosis

Blood-brain barrier permeability is highly confusing

The fat solubility of the substance: The solute in the blood must pass through the endothelial cells of the brain capillary to the brain tissue, and the endothelial cell membrane is a lipid-based bilayer membrane structure, which is lipophilic and easily passes through the fat-soluble substance. Therefore, the fat solubility of the solute in the blood determines the difficulty and speed of its passage through the barrier. The higher the fat-soluble solute, the faster the solute enters the brain tissue through the barrier. According to this rule, certain central nervous system drugs can be modified to make it easier to enter the brain tissue for faster drug effects. For example, barbital is a central anesthetic but its lipophilicity is weak, so it is very slow to enter the brain tissue, but if it is transformed into phenobarbital, it is easier to pass through the blood-brain barrier because of its strong lipophilicity. The brain tissue quickly exerts its hypnotic anesthetic effect. Another example is the transformation of morphine into diacetylmorphine, which is easier to achieve its analgesic effect by reaching the brain tissue through the lipophilic endothelial cell membrane.

Hydrophilicity of a substance: No matter whether it is a positively or negatively charged solute, it dissolves with water and forms a hydrogen bond with the oxygen atom of the water molecule. The more the charge of the solute, the stronger the ability to form a hydrogen bond, and the more water-soluble. Strong, the ability to pass the blood-brain barrier is also worse. However, water itself and solute such as glucose have a small molecular weight and can enter the brain through the junction of endothelial cells and astrocytes. Adrenaline and norepinephrine are difficult to pass through the barrier into the brain due to their high water solubility and high hydroxyl content. Amino acids can cross the blood-brain barrier, but amines are difficult.

Degree of binding to plasma proteins: Many compounds in plasma bind to plasma proteins. Small molecule compounds, such as hormones, do not easily cross the blood-brain barrier after binding to plasma proteins, so they do not exert their physiological effects; they must be freed before they can exert their effects through the barrier. For example, thyroxine, more than 99% in plasma combined with plasma protein, less than 1% free; thyroxine content in cerebrospinal fluid is low, but similar to the free thyroxine content in plasma, it can still meet physiological needs. Free thyroxine easily enters the interstitial fluid of the brain. Any drug that prevents the binding of thyroxine to plasma proteins can increase free thyroxine in the plasma and increase the dose through the barrier.

Carrier Operating System: Brain capillary endothelial cells have a variety of carrier proteins that can transport bloodborne substances out of endothelial cells. Carrier proteins have high selectivity. A carrier protein can only transport one substance. The specific carrier protein of brain vascular endothelial cells can make some substances that are difficult to pass the blood-brain barrier smoothly transport into the brain quickly. For example, glucose is The main energy source of brain tissue metabolism is originally slower through the blood-brain barrier, but the glucose carrier can quickly meet the brain metabolism needs through the blood-brain barrier. Affirmed carriers include: hexose carriers, neutral amino acid carriers, basic amino acid carriers, and short-chain monocarboxylic acid carriers, all of which facilitate the smooth passage of suitable transport materials through the blood-brain barrier.

Under normal circumstances, the central transmitter can hardly pass the blood-brain barrier, which is conducive to maintaining the stability of the central transmitter level in the brain and eliminating the interference of extra-brain stimulation factors. Therefore, it may be related to the enzyme system in brain capillary endothelial cells. It has been found to contain monoamine oxidase, and various central transmitters are monoamines, such as catecholamines, serotonin, histamine, etc., which can be eliminated by monoamine oxidase. Live, this biochemical transformation in the cytoplasm of endothelial cells strengthens the function of the blood-brain barrier, which can stabilize the environment inside the brain tissue, and is less affected by the dramatic changes in the content of substances with strong physiological effects in the circulating blood.

1 using a smaller molecular weight horseradish peroxidase (a protein, molecular weight of about 40,000, molecular diameter of about 500 ~ 600 nm) or a fragment thereof as a marker for permeability of the capillary wall, a small molecular weight horseradish peroxidase fragment It can quickly enter the muscle tissue through the capillaries of the muscle, but this enzyme fragment in the brain capillaries is blocked in the blood vessels and cannot enter the brain tissue. In this barrier action, the basement membrane and the perivascular foot intermittent membrane only play a supporting role.

2 The pinocytosis of brain capillary endothelial cells is weak. Therefore, there is little material exchange between vascular endothelial cells and brain tissue. After ionizing radiation, the animals increased their vesicles and the permeability of the blood-brain barrier increased.

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