THE "MAIN PC" OF HUMAN BODY AND ITS DISOROERS

by Gennady POROSHENKO, Dr. Sc. (Biol.), Research Institute of General Reanimatology, Russian Academy of Medical Sciences (Moscow)

The plants and Protozoa maintain homeostasis (capacity to preserve constancy of humor under conditions of permanent metabolism involving exogenous substances and energy), obligatory for the existence of all representatives of the organic world, due to physico-chemical mechanisms, unlimited propagation and filling up of the entire space around them. Higher animals and humans have a special structure for regulation of processes in the body and its interactions with the environment-the nervous system with its central compartment-the brain.

The student at an exam in physiology was asked: "What rudimental organs do you know?" (i.e., organs inherited from animal ancestors, underdeveloped and seemingly not needed). He answered: "For example, brain." It may seem that this anecdote is not so far from the truth: sometimes, removing an appreciable part of the brain (of course, without involving vital zones), neurosurgeons observe no apparent disorders in thinking and other capacities in patients. The matter is that we still know almost nothing about some vast areas in the brain*.

Meanwhile, the central compartment of the nervous system controls maintenance of health: it reacts to any changes in the body, as it is connected with all its compartments by numerous nerves and the so-called endocrine bonds due to hormones and hormone-like protein substances circulating with blood in the vessels. In addition, it receives signals from organs of senses and, certainly, is responsible for thinking (mental) processes, which is still unknown to medical science**.

It is therefore clear why irreversible disorders in this "main PC" of human body is now regarded as the main

* See: M. Ostrovsky, "The Brain Science: Current Trends", Science in Russia, No. 4, 2010.–Ed.

** See: S. Medvedev, "Mechanisms of Brain Activity", Science in Russia, No. 4, 2010.–Ed.

Brain structure.

sign of death. It is not a problem today to trigger the heart that has stopped beating and restore respiration in a majority of cases, but we still cannot resuscitate the brain cortex sites dead from hypoxia (insufficient oxygen supply to the cells). That is why critical and terminal (borderline between life and death)* states are so dangerous for the brain, along with traumas, tumors, and many other diseases, affecting the brain perhaps more than any other organ.

When oxygen supply is resumed, the central compartment of the nervous system is damaged by free radicals and becomes one of the triggering mechanisms of post-resuscitation disease development**. Therefore, Academician (Academy of Medical Sciences of the USSR) Vladimir Negovsky, the founder of national reanimatology, famous pathophysiologist, who discovered this phenomenon, regarded the brain not only as an object, but also as a subject of emergence of this disease and its consequences.

The peculiarities of behavior, morphological changes in the structures of animals with a history of critical states have been studied at our Institute for many years. Great attention is paid to systemic circulation arrest as a result of electric traumas, mechanical asphyxia***, acute blood loss, compression cerebral ischemia****.

Recent studies based on new methods have shown that in such cases, when energy resources are absent (oxygen supply is arrested), pathological reactions develop in the gray matter tissue of the central compartment of the nervous system, first of all, changes affect physico-chemical characteristics of molecules (mobility in electric field, polymerization*****), impairment of cell membrane permeability and of intracellular structures. The more severe is the terminal state, the more intense are these processes. During the post-re-suscitation period they manifest themselves in the form of neurological disorders of different extent.

In addition, the reduction of nucleic acid levels was fixed in brain cells of the animals under study. This

* See: G. Poroshenko, "Medicine of Critical States", Science in Russia, No. 5, 2004; " Between Life and Death", Science in Russia, No. 1, 2006.–Ed.

** Post-resuscitation sickness is a process unfolding in a patient after clinical death and resuscitated due to a complex of reanimation measures; it is characterized by functional disorders of vital organs and systems, specifically, memory.–Ed.

*** Asphyxia is caused by oxygen starvation and carbonic acid excess in blood and tissues as a result of compression of the respiratory tract from without (strangulation), blocking of its lumen by edema, etc.–Ed.

**** Compression cerebral ischemia is compression of a blood vessel by a tourniquet, cicatrix, tumor, foreign body, exudate (opalescent protein-and cell-rich liquid produced at the site of inflammation).–Ed.

***** Polymerization is formation of high-molecular substance (polymer) by repeated joining of molecules of low-molecular substance (monomer, oligomer) to the active center at the terminal of the growing chain.–Ed.

reduction persisted even after timely and full compensation for blood loss (in the course of the first hour), which normalized the energy potential of the body. In addition to the progress of the initial biochemical pathologies, new ones formed during the immediate post-resuscitation period (14-21 days), leading primarily to the DNA destruction. The neurochemical transformations of the remote (3-4 months) period were both reparative and destructive: the activities of the studied enzymes and total RNA level normalized, but secondary reduction of a number of protein fraction levels progressed and the DNA concentration continued to drop, which made a rehabilitation therapy a necessity.

On the other hand, reduction of DNA content in experimental animals after resuscitation was paralleled by the formation of extensive foci of neuron death in the brain cortex (neurons are the main elements of the nervous system). Further observations showed that the process did not stop even later–in the course of 3-4 months–and progressed in the absence of hypoxia and in the presence of compensatory and reparative processes. After studies of this phenomenon, our specialists stated that the neuronal DNA structure could be destroyed even if there were no inflammatory reactions.

The "root of malice" in this case is stimulation of the enzymes involved in the destruction of nuclear DNA. We mean, among other things, its cleavage into structural subunits–nucleosomes; this process is the basis of apoptosis (i.e., programmed death of certain cells, not involving adjacent cells; it is compared to the leaves falling off in autumn, when dying leaves quietly come off the branch, without damaging other leaves). The cause of this phenomenon is presumably a steady self-destruction of neurons. Vyacheslav Kozhura, Dr. Sc. (Med.), a staff member of our Institute, and his colleagues, demonstrated for the first time in 2000 that critical states led to an increase in the incidence of apoptosis in the brain of experimental animals.

The hypothalamic cell nuclei are more resistant than other structures to ischemia (local deterioration of blood supply, leading to transitory dysfunction or stable injury) in case of massive blood loss. However, destructive changes in the cerebral cortex progress more rapidly than in the liver and hypothalamus. The matter is that the work of the central compartment of the nervous system needs a tremendous amount of energy, and it is extremely sensitive to the slightest failures in energy supply, which can cause grave injuries.

It is known that energy requirements of all living organisms are implemented at the expense of the Sun. The founder of the Russian school of plant physiology Kliment Timiryazev*, Corresponding Member of St. Petersburg Academy of Sciences (from 1917), called the green leaf Prometheus, stealing fire from the Heaven for humans. Under the effect of the Sun, water and carbon dioxide molecules binded to each other in plant cells synthesize nutrients, which then get into animal and human organisms (while oxygen, as a "byproduct" of the reaction, is released into the atmosphere).

* See: A. Druchek, "Sun, Life and Chlorophyll", Science in Russia, No. 4, 2008.–Ed.

Brain connection with organs of senses.

A reverse process takes place in our cells: compounds forming as a result of consumption of plants decompose under the effect of oxygen into carbon dioxide and water with the formation of important products essential for vital activity, primarily adenosine triphosphate*. It is produced in mitochondria–"power plants", which need oxygen for functioning. It is therefore clear that hypoxia (an essential manifestation of critical states) is dangerous for them.

A lot of people were in situations between life and death. Thus, in the USA, 2 percent of population take a course of intensive therapy and pass through resuscitation department. Unfortunately, such statistical data for Russia are unknown, but presumably, the percentage is similar. The majority of such patients suffer from different diseases, and if these are mental diseases, they can be cured. However, significant cognitive and emotional disorders can emerge and persist in subsequent life. Hence, we can speak about an important social problem.

Brain dysfunctions (primarily deterioration of short-term and long-term memory, intellectual abilities, reduction of the attention concentration) are often observed after cardiosurgical interventions in the conditions of artificial blood circulation. This allows to regard them as an individual case of complications, developing in hypoxia (presumably caused by transitory failures of the cerebral bloodflow during surgery). Studies of these conditions in such patients are un-fold-ed at our Institute. According to the published data, 30-80 percent of them suffer from cognitive disorders, but mechanisms of their development remain unclear.

Ultrasonic studies have revealed that operations in conditions of artificial blood circulation are always associated with thromboembolism**, one of the main factors of brain injury. The development and use of a complex of measures preventing it led to reduction of the incidence of severe neurological complications (to 0.3 percent of patients) in our country; cognitive dysfunction remains rather prevalent (up to 79 percent).

One more important cause of neuropsychological changes in the patients under consideration is diffuse hypoxia of the central compartment of the nervous system, resultant from insufficient supply of oxygen-rich blood to this compartment during the intervention. It is particularly important for elderly patients with atherosclerotic involvement of the respective vessels. In addition, a method of anesthesia, minimally modulating the cerebral bloodflow, has to be selected. Observations by our scientist Alexei Mozalev, Cand. Sc. (Med.), confirm this fact: cognitive functions are less impaired in the patients aged over 60, who underwent an operation under combined narcosis. And, finally, one should remember that blood circulation recovery (reperfusion) is paralleled by the production of active oxygen forms in the "main PC" cells, and these forms can impair intracellular structures.

A lot of scientists think that the main cause of failures of cognitive functions is apoptosis in the brain cells, which, in its turn, results from reduced energy potential of mitochondria, formation of active oxygen forms, and direct stimulation of respective genes. The genetic status of the body and expression are modified significantly during critical and terminal states and these shifts are associated with direct damage inflicted to some genes, including those responsible for factors of apoptosis. This leads to significant morphological and functional disorders in the work of the central compartment of the nervous system, essential for the development of the post-reanimation disease.

All this means that the brain is an extremely intricate structure, not only determining the pattern of mental and emotional reactions, but also regulating all processes in the organism and largely remaining a mystery for us. Nevertheless, prevention of its disorders is one of the priority problems in the treatment of critical and terminal states.

* Adenosine triphosphate is a nucleotide playing an exceptionally important role in energy and substance metabolism in organisms; a universal source of energy for all biochemical processes in living systems.–Ed.

** Thromboembolism is acute obstruction (embolism) of the blood vessel by a clot detached from the site of its formation (heart or vascular wall) and released into circulating blood. As a result, the bloodflow in the vessel is blocked, tissue ischemia emerges in the basin of this vessel, often eventuating in its infarction.–Ed.