The role of the blood-brain barrier in the generation of a constant brain potential level

Let us turn to the consideration of those experiments in which the AMR arising on the BBB is studied. Anatomically, the BBB is a complex of capillary endothelial cells with their basement membrane and an adjacent layer of astrocytes. It is assumed that the basement membrane is common to both astrocytes and endothelium. The transport of substances through the endothelium, which forms the BBB, is controlled by three types of cells (astrocytes, pericytes and neurons), which have direct contact with the endothelium to the apillaries . The endothelium of the cerebral vessels is much thicker, and its permeability is much less than in other organs and tissues of humans and animals . Due to this, conditions are created for a significant voltage drop on the BBB membrane, in contrast to histohematological barriers, the electrical resistance of which is much less.

According to many researchers, a stable potential difference of the millivolt range appears at the BBB boundary. Measurements of this potential difference were carried out with the active electrode located on the surface of the brain or in the cerebral ventricles, and the reference electrode inside the vessels, often in the veins. The potential difference was sensitive to changes in the concentration of various ions on both sides of the membrane. This allowed us to suggest that the potential difference at the BBB boundaries arises due to different concentrations and diffusion rates of different ions through the BBB, i.e. this potential difference behaves as a diffusion or membrane-diffusion potential . Let us briefly consider the main experiments obtained by these authors in studying the BBB potentials.

The potential difference between the different parts of the central nervous system and the blood of the jugular vein was measured in rats, rabbits, cats and dogs. It was found that in these animals the surface of the brain is more negative (by 1-5 mV) than the blood of the jugular vein. This potential difference is sensitive to alveolar CO 2 voltage , but depends on the concentration of H + to a greater extent + than on CO 2 . While an increase in the concentration of H ions in the blood led to a positive shift in the potential of the brain with respect to blood, the application of acidic solutions to the cortex decreased the positivity of the central nervous system. The same relationships were found with the intravenous administration of a solution containing K + ions and with its application to the cortex. Anoxia and cessation of blood circulation caused a negative shift in the potential difference, reaching 15 mV, which did not return to zero and one day after the death of the animal. Simultaneous measurement of arterial blood pH, cerebral cortex pH and the difference in potential of the BBB revealed the following relationship between these values:

 RP = k  log [H + ] а / [H + ] l , where RP is the potential difference between cerebrospinal fluid and blood, [H + ], a is the concentration of H + in arterial blood, [H + ] l is the concentration of H + in the cerebrospinal fluid;  RP – change in the potential difference.

This pattern is in accordance with the Nernst equation. The authors assumed that the source of constant potentials is the diffusion potential created by the [H + ] and [HCO 3 – ] ions on both sides of the BBB .

The dynamics of the SCP recorded between the cortex and blood of the jugular vein (upper curve), and the pH difference between the cortex and blood of this vein (lower curve) with the intravenous administration of 0.1 normal hydrochloric acid solution.

On the abscissa axis is the time in minutes, on the ordinate axes: on the left is the pH, on the right is the SCP in millivolts. Perfusion of hydrochloric acid was carried out from the second to the fifteenth minute. Measurement of the SCP was made by non-polarizable electrodes, the reference electrode was in the jugular vein .

Diffusion potential arises only when the mobility of anions and cations is different in the applied solution . This condition was met by applying hydrochloric acid to the brain, since hydrogen and chlorine ions have different mobilities. When there is a different concentration of the same compounds with the same mobility of anions and cations on both sides of the membrane, the diffusion potential does not arise.

The evidence that the BBB potential is due to different concentrations of hydrogen ions on both sides of the barrier caused the appearance of a large number of studies summarized in the monograph by M. Bradbury , a brief summary of which is given below.

In the work of, the acidity of the cerebrospinal fluid was changed by injecting bicarbonate into the brain ventricles, which shifts the pH to the alkaline side. At the same time, no noticeable shifts in the BBB potential occurred. These authors put forward the idea of ​​the asymmetric sensitivity of the BBB membrane to the concentration of hydrogen ions, since in the same experiments it was shown that with metabolic and respiratory acidosis in the blood, the positivity of SCPs recorded from the brain increased also showed that in many animals, including rats, the cerebrospinal fluid potential is positive with respect to blood. In 5 goats, the potential difference recorded between the liquid of the large cistern and the blood of the external jugular vein was +6.8 mV; between the fluid of the lateral ventricle and the same blood, it was +6.1 mV. In healthy anesthetized 40 dogs, it ranged from -2 to +7 mV for a large tank. In general, fluctuations in this indicator could be attributed to fluctuations in the pH of arterial blood. At normal arterial blood pH (7.4), the potential was +4 mV. The sensitivity of the potential difference to the pH of arterial blood in acute metabolic disorders was 43 mV per unit pH, and for respiratory – 32 mV per unit pH .

local_offerevent_note September 16, 2019

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