Changes in cerebral energy metabolism under stress

Stress (general adaptive syndrome) is a set of stereotypical adaptive reactions that occur in the body in response to the action of an extreme stimulus of any nature. Factors causing a stress reaction are called stressors. As stressors, emotional stress, significant mental and physical efforts, injuries, intoxications, any disease, etc. can act.

The fundamental studies that laid the foundation for the concept of stress were made by Canadian physiologist Hans Selye (1960). The author described three main stages of stress: (1) anxiety, (2) resistance and (3) exhaustion. He also showed that the central role in the mechanisms of stress is played by the activation of the hypothalamic-pituitary-adrenal system (GGNS ), which leads to significant changes in the hormonal background in the body.

An anxiety reaction characterizes the acute proceeding mobilization of adaptation processes in response to the action of a stressor. At the stage of resistance, an increased resistance of the body to the stressor is established. With severe and prolonged stress, the general adaptation syndrome goes into the stage of exhaustion, when the body’s resistance drops sharply.

Later it was found that the hippocampus and amygdala, the structures of the limbic system involved in the regulation of anxiety, fear and depression, take a large part in the regulation of the activity of GNSS. Central amygdala nucleus enhances the activity of the HPA axis C . It has direct projections into the paraventricular nucleus of the hypothalamus, where the bodies of neurons containing corticotropin releasing factor, a substance that provides ACTH release by hypophysis, are located . Hippocampus through kortikogipotalamichesky tract has direct projections to the paraventricular nucleus and projections to the nucleus of terminal strips, which are also associated with paraventrikulyar nym nucleus hypothalamus sa . The hippocampus, in general, has a inhibitory effect on the activity of GNSS, exercising control by the mechanism of negative feedback .

Consider the sequence of events during the development of stress. Under the influence of an extreme stimulus (stressor) from the brain substance of the adrenal glands and formations of the sympathetic nervous system, the release of the “emergency” hormone adrenaline increases. The activity of the noradrenergic system also increases. Although the BBB prevents the adrenaline and norepinephrine secreted by the ends of the sympathetic nerve fibers and the adrenal medulla from entering the brain, these substances are able to penetrate the BBB in some of its areas – in the so-called circumventricular areas. Adrenaline and norepinephrine activate the structures of the limbic-reticular complex, in particular the tonsils and cerebral cortex. As a result of this, the activation of GGNS is mediated by an exciting mediator – nitrogen oxide . From the paraventricular nucleus of the hypothalamus allocated corticotropin-releasing factor that triggers the release of pituitary ACTH, which increases secretion of glucocorticoids by the adrenal cortex s . These hormones, in particular cortisol, affect the hippocampal neurons. In turn, it inhibits the activity of the hypothalamic-pituitary-adrenal axis by the mechanism of negative feedback.

Stress hormones provoke a variety of changes in the body: adrenal hypertrophy develops, the thymus and lymph nodes involve, the inflammation slows down, and the functional state of the central nervous system changes. (A detailed discussion of these changes is beyond the scope of this work, and the energy aspects of this problem will be considered in this section.)

Achievement of adaptation under stress is carried out primarily due to the restructuring of energy metabolism in the body. Adrenaline causes hyperglycemia and inhibition of insulin secretion. A decrease in insulin concentration due to a decrease in the antilipolytic effect ensures the intensification of lipolysis under the action of lipolytic “stress” hormones. As a result of this, the energy needs of the body are provided by non-esterified fatty acids. Even in the brain, in addition to glucose, fatty acid decomposition products – ketone bodies – begin to be used as an energy source. Under the influence of cortisol, gluconeogenesis intensifies, the structural substrate for which is mainly amino acids. In general, cortisol has a catabolic effect . Protective reactions under stress can be carried out with increased blood flow, which is provided by an increase in blood pressure under the influence of activation of the sympathoadrenal system.

Under stress, the functional state of the brain and its energy metabolism naturally change. Using PET in people in this state, an increase in cerebral blood flow was detected in various parts of the brain, in particular in the frontal areas . Glucocorticoid hormones of stress increases the excitability of brain structures up to reduce the convulsive pore hectares . In stress hippocampus, the activity of glutamatergic neurons increases, and this effect is at least partially mediated by glucocorticoids, since it decreases in animals with removed adrenal glands . Glutamate is an exciting mediator that plays an important role in memory processes. This has been shown, in particular, on post-tetanic potentiation models. However, at elevated concentrations, this mediator has a neurotoxic effect mediated by excessive activation of NMDA receptors, accumulation of intracellular calcium and activation of Ca-dependent phospholipases, proteases, and endonucleases. Under the influence of these enzymes, the most important structures of neurons degrade and die. The neurotoxic effect of glutamate increases with increasing levels of glucocorticoids. So, in animals under conditions of natural social stress, as with chronic administration of corticosterone in a dose corresponding to its increase under stress, the development of atrophic changes in the hippocampus is observed; the result is a disruption in the learning process, and this effect is observed only in elderly animals . The increased concentration of glucocorticoids in the brain starts the processes of programmed cell death – apoptosis.

Under stress, the role of glycolysis in energy metabolism increases. This factor, as well as the use by the brain as an energy substrate of ketone bodies, leads to an increase in the concentration of acidic metabolic products in the brain .

Reduction in intracellular pH disrupts the mitochondrial respiratory chain, which enhances the process of free-radical oxide Niya . In addition, acidosis increases intracellular calcium and is a contributing factor to apoptosis.

Investigation of changes in brain SCP parameters under stress associated with waiting for an alarm

Our study compared the parameters of SCP in the rescuers of the Moscow Region, whose work is associated with the elimination of accidents in mines and is characterized by a high level of stress, and in the control group of healthy subjects – construction workers, whose professional activity is not associated with significant psychoemotional stress.

A characteristic feature of the work of mine rescuers is the expectation of an “alarm” signal – the need to suddenly and quickly switch from one type of activity, usually safe, to another type, associated with risk and danger to life during the liquidation of the mine accident. The constant expectation of an alarm leads to the development of stress (“Guidelines for the organization and conduct of professional selection of operational workers of paramilitary mine rescue units”, 1973).

13 mountain rescuers (average age 38.1 + 2.1 years) and 24 construction workers of the same age (36.4 + 2.5 years) were examined. In addition to the study of SCP in both groups, the state of the autonomic nervous system was evaluated by measuring heart rate, blood pressure and the Kerdo index, the value of which allows us to judge the predominance of the tone of the sympathetic or parasympathetic nervous system.

An analysis of vegetative indicators has confirmed the presence of stress among rescuers. In this group, the pulse was significantly increased compared with the control group of non-stressed healthy people of the same age. They had a significantly higher Kerdo index than in the control, which indicated greater activation of the sympathetic nervous system . Blood pressure indices in both groups did not significantly differ.

Autonomic indicators in rescuers and in the control group of healthy subjects

In rescuers under stress, the SCP was significantly increased in all monopolar leads, an increase in the averaged SCP was also noted (Fig. 6.8). In addition, they revealed a correlation between the Kerdo index value and the level of potential in the frontal region measured unipolar ( r = 0.6; p <0.05). In the control group of non-stressed healthy subjects, there was no such relationship.

AMR in mine rescuers and in the control group of healthy subjects.

On the ordinate axis – SCP values ​​in mV, on the abscissa axis – various leads of SCP

The increase in AMR in rescuers is obviously due to the fact that stress increases cerebral energy metabolism and cerebral blood flow, and the role of glycolysis and other metabolic pathways accompanied by the accumulation of acidic metabolic products in the brain structures increases. A significant increase in SCP was noted in all areas except the frontal, which indicates an increase in energy metabolism and a decrease in pH in most parts of the brain.

local_offerevent_note September 8, 2019

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