Decreased functional activity of the brain

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A decrease in the functional activity of the brain is accompanied by a decrease in local cerebral blood flow and glucose consumption, while the pH rises. Such changes occur under the influence of sedative drugs during at rkoze etc .

Extracellular and intracellular pH are interconnected. Thus, upon activation of hippocampal pyramidal neurons, an increase in intracellular Ca 2+ associated with depolarization is accompanied by a noticeable drop in intracellular pH in these neurons. Such acidification is caused by the exchange of intracellular Ca 2+ for extracellular protons through the Ca 2+ / H + pump mechanism . The powerful neuromodulatory effect of H + increases the possibility of changes in excitability and synaptic plasticity .

With increased activity of neurons, a change in the acid-base balance in a certain way is associated with the use of macroergic phosphates. Already in the first seconds of an increase in functional activity, a decrease in phosphocreatinin is observed in all subjects with or without a change in pH. According to theoretical calculations, short phase nervous activity requires more energy, at least three times higher than the initial level of consumption. During short activation, vascular reactions precede a significant decrease in the content of intracellular macroergic phosphates. As the duration of stimulation increases, the amount of energy required decreases. The phosphate level returns to normal in parallel with the restoration of vascular reactions .

The sensitivity of many ion channels to protons, their modulation with pH can affect the functional activity of the brain, especially when the pH shift is large enough and fast. It was shown that intraneuronal acidosis suppresses the functional activity of hypocampal neurons . When measuring pH with ion-selective electrodes, a noticeable cellular and regional activity variability was detected, depending on the pH shift. There is speculation that the extracellular pH is regulated by glial cells, ligandozavisimymi ion channels, as well as intra- and extracellular carbonic anhydrase th .

In the conditions of pathology, acidosis can also develop with a low functional activity of the nervous tissue. For example, in organic diseases of the central nervous system, a change in the acid-base balance is determined by the nature and severity of the pathological process. As a rule, with meningitis, persistent cerebral acidosis occurs. With cerebral tumors in the brain, generalized acidosis of the brain is observed, but in the area of ​​the tumor – alkalosis. With cerebral ischemia, the development of acidosis is characteristic. While normal decrease in pH is associated with an increase in the functional activity of the brain, energy metabolism and local cerebral blood flow, then with pathology, lactic acidosis is usually associated with low cerebral blood flow and a transition to the glycolytic pathway of metabolism.

Changes in pH affect many metabolic processes. Even mild acidosis disrupts the respiratory chain of mitochondria, as a result of which the formation of free oxygen radicals, damaging the cell, is intensified. A more pronounced acidosis (pH 6.5) causes the death of neurons by necrosis or apoptosis – programmed cell death . Acidosis promotes the formation of sparingly soluble amyloid protein, disrupting the normal metabolism of the amyloid precursor protein, which plays a role in the pathogenesis of Alzheimer’s disease.

The processes of obtaining energy in the brain and other organs are basically similar. When splitting high-molecular substances – glucose, fatty acids and ketone bodies, as well as certain amino acids, nineteen energy is released, which accumulates in the form of macroergic compounds – ATP and creatine phosphate, and then is spent to maintain the structure of the cell and ensure its functions. By the intensity of energy processes, the brain takes a leading place in the body. The highest metabolic rate was found in the cerebral cortex, the lowest in the spinal cord. Peculiarities of brain energy exchange are that it practically does not contain a supply of substances used as energy substrates and needs to be continuously supplied through the cerebral bloodstream, in addition, the brain’s energy needs are satisfied mainly due to glucose catabolism (85-90%). As additional energy substrates, the brain uses amino acids, mainly glutamate, as well as free fatty acids and ketone bodies.

Aerobic and anaerobic digestion of glucose is accompanied by the accumulation of acidic metabolic products – lactic acid during glycolysis and carbonic acid during the Krebs cycle. However, there are mechanisms that maintain the acid-base balance in the brain and in the body as a whole at a fairly constant level. This is gas exchange of the lungs and excretory functions of the kidneys, as well as the buffering properties of body fluids, depending on the presence of bicarbonates, inorganic phosphates and proteins, which combine with an excess of acids or bases and form substances that do not affect pH. In addition, there are specific mechanisms for maintaining pH in the brain and cerebrospinal fluid. This selective BBB permeability, targeted ion transport and compensatory changes in metabolism. Transport systems that carry out targeted transport of HCO 3 – and H + ions through the BBB play a significant role in maintaining cerebral pH. Their activity, obviously, is carried out due to changes in the electrochemical potential at the BBB border, which helps to remove or vice versa the absorption of hydrogen ions from the brain and cerebrospinal fluid into the blood.

A close relationship has been established between the functional activity of the brain, its energy metabolism and cerebral blood flow. When neurons are activated, their depolarization occurs, as a result of which potassium ions accumulate in the intercellular fluid, which are a trigger factor in enhancing cerebral blood flow. In neurons, aerobic and anaerobic oxidation of glucose increases, accompanied by the accumulation of acidic metabolic products – lactate and carbon dioxide. An increase in the concentration of hydrogen ions contributes to a prolonged increase in cerebral blood flow.

Despite the activity of mechanisms aimed at maintaining a constant pH, with an increase in the functional activity of the brain, as well as with many types of pathology (epileptic seizures, ischemia, meningitis), the brain pH shifts to the acid side – acidosis develops. Acidification reduces the functional activity of neurons, affects metabolic processes, in particular, enhances free radical processes, and in cases of significant changes in pH causes the death of neurons by the mechanisms of necrosis or apoptosis.

local_offerevent_note September 24, 2019

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