RU2319441C2 - Method for determining state of nerve tissue function and metabolism - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves recording electroencephalogram EEG and constant potential level CPL and comparing them with respect to measurement parameters variability and functional and metabolic condition is determined during the same time interval. CPL becoming shifted in negative direction and EEG power increasing, in accompanying neuron activity depolarization, bad functional and metabolic nerve cells condition is determined. CPL becoming shifted in negative direction and EEG power falling, in accompanying neuron activity depolarization, worse functional and metabolic condition is determined. CPL becoming shifted in positive direction and EEG power increasing in accompanying repolarizing neuron activity after depolarization inhibition or hyperpolarizing activity, good functional and metabolic nerve tissue condition is determined. CPL becoming shifted in positive direction and EEG power falling in accompanying repolarizing neuron activity after depolarization activation or hyperpolarizing inhibition, very good functional and metabolic nerve tissue condition is determined.

EFFECT: qualitatively new approach to determining nerve tissue condition.

3 dwg, 1 tbl

Description

The present invention relates to medicine, namely to neurology, psychopathology, neurosurgery, neurophysiology and experimental neurobiology, as well as psychophysiology and is intended to determine the functional and metabolic state of the nervous tissue in normal and pathological conditions.

A known method for determining the functional and metabolic state of nervous tissue by performing positron emission tomography of the brain / Buchsbaum MS, Gillin JC, Wu J, Hazlett E, Sicotte N, Dupont RM, Bunney WE Jr. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography // Life Sci 1989; 45 (15): 1349-56 /.

The disadvantage of this method is the difficulty of implementation, high economic costs and the use of expensive equipment for the study, the need for preliminary preparation of patients for the study. The disadvantages of the method are the impossibility of dynamic monitoring of the state of the brain during medical manipulations in the clinic, the complexity and inconvenience for implementation in experimental studies on small laboratory animals.

A known method of recording the total slow electrical activity of the brain from the surface of the head (EEG) / Human brain biopotentials. Mathematical analysis. // Ed. Rusinova B.C., M .: Medicine, 1987, 254 p. /. It is known that activation processes in the nervous system are accompanied by depression of alpha activity. The development of pathological conditions in connection with metabolic disturbances, as in brain ischemia, is associated with the appearance of slow-wave activity of the theta and delta ranges. Inhibition of the functional state with deepening hypoxia and ischemia leads to depression of EE.

Despite the fact that this method has a number of positive properties, it does not allow subtly differentiating many physiological and pathological FS.

The closest analogue is a method for determining the functional and metabolic state of nerve tissue / RF Patent No. 2245673, A61B 5/04, A61B 5/0476, 2005 /, including registration of an electroencephalogram (EEG), simultaneously with the EEG, the level of constant potential (SCP) is recorded and with negative SCP and an increase in EEG power, the depolarization activity of neurons and increased metabolism are determined; with negative SCP and a decrease in EEG power, depolarization inhibition of neurons and inhibition of metabolism; with positivization of SCP and increase in EEG power, repolarization or hyperpolarization activation of neurons and increased metabolism; with positivities of SCP and a decrease in EEG power, hyperpolarization inhibition of neurons and a decrease in the metabolism of nerve tissue.

However, the known method determines only the change in the needs of cells of the nervous tissue from a quantitative point of view, without characterizing the functional and metabolic state of the cells from a qualitative point of view. So in this method, an increase in metabolism is observed both with the negation of SCP and an increase in the power of EEG rhythms, and with the positivization of SCP and an increase in the power of EEG rhythms. Whether the nervous tissue is in the same functional state (FS) is not clear. The concept of FS requires a qualitative description of current activities / Medvedev V.I. Functional states of the operator // Ergonomics: Principles and recommendations. M., 1970. Issue 1. S.127-160; Doskin V.A., Lavrentieva N.A., Miroshnikov M.P., Sharay V.B. Functional differential self-assessment test. // Questions of psychology, 1973, No. 6, p.141-145; Medvedev V.I., Leonova A.B. Functional conditions of a person. In: The Physiology of Labor. St. Petersburg: Nauka, 1993, p. 25-61 /. Characterizing the metabolic and FS of nerve cells from these positions, it is necessary to describe whether they are in good condition or poor. In the known method, this is not determined.

The objective of the invention is to create a method that allows you to characterize the current metabolic and FS of the nervous tissue from a qualitative point of view, by recording and differentiating the nature of changes in SCP and EEG.

The problem is achieved in that in the known method for determining the functional and metabolic state of nerve tissue, including the simultaneous registration of an electroencephalogram (EEG) and constant potential level (SCP), polarization and activation processes observed by the nature of changes in SCP and EEG are compared with the state of lability and resistance nerve cells and their biochemical systems and give a qualitative characteristic of metabolic and FS of nervous tissue.

Positivization of SCP and a decrease in the power of EEG rhythms are considered either as the formation of hyperpolarizing inhibition of neurons and the development of excellent metabolic and PS of nervous tissue, or as repolarization of the membrane after a period of depolarization excitation and improvement of metabolic and PS of nervous tissue.

The positivization of SCP and the increase in the power of EEG rhythms are considered either as post-hyperpolarization activation of neurons and the development of good metabolic and FS in them, or as the development of repolarization activation of neurons and improvement of their metabolic and FS after depolarization inhibition (parabiosis).

Negatiation of SCP and increase in the power of EEG rhythms are considered as the development of depolarization activation of neurons and poor metabolic and FS of nervous tissue.

An even greater negativity of SCP and a decrease in the power of EEG rhythms are considered as the development of depolarization inhibition and very poor metabolic and FS of the nervous tissue.

A comparison of the polarization and activation processes observed by the nature of changes in SCP and EEG with the state of lability and resistance of nerve cells and their biochemical systems allows us to give a qualitative characteristic of metabolic and FS of nervous tissue.

The method is as follows.

Using a direct current amplifier, a non-polarizing (silver chloride) electrodes are simultaneously used to record the level of constant potential and total slow electrical activity (EEG) in the studied nerve tissue.

With positive changes in SCP and inhibition of EEG power, accompanying an increase in the resting potential of cells (re- or hyperpolarization) and inhibition of neuronal activity, either an improvement in the metabolic and FS of the nervous tissue in the case of a return of the membrane potential to the level of the resting potential after depolarization excitation of excitability, or the development of excellent metabolic and FS in the case of hyperpolarizing inhibition of cells.

With positive changes in SCP and an increase in EEG power, accompanying an increase in the resting potential of cells (re- or hyperpolarization) and activation of neuronal activity, the improvement of metabolic and FS in connection with the release of cells from parabiosis, or good metabolic and FS in the case of hyperpolarization excitability, is determined.

With negative changes in SCP and an increase in EEG power, accompanying a decrease in resting potential (depolarization) and activation of nerve cells, the development of poor metabolic and PS cells of the nervous tissue is determined.

With negative changes in SCP and inhibition of EEG power, accompanying a strong decrease in the resting potential (strong depolarization) of cells and inhibition of neuronal activity (by the type of parabiosis), the development of very poor metabolic and PS cells of the brain is determined.

Example

It has long been known that anesthetics of the barbiturate series when acting on nerve cells cause their hyperpolarization / Sato P., Austin G., Yai H. Increase in permeability of the postsynaptic membrane to potassium produced by "nembutal" // Nature, 1967, 215, p. 1506-1509 / and inhibition of neuronal activity. At the same time, it is shown that these substances have a neuroprotective effect / Samushiya O.Sh. Ultrastructural manifestations of the treatment effect of ischemic brain damage with sodium oxybutyrate // Questions of modern neurology. Collection of scientific papers. Tbilisi, 1985, p. 184-190 /. Adenosine and its analogues also exert hyperpolarizing inhibition and neuroprotective effect / Kulinsky V.I., Usov L.A., Sufianova G.Z., Sufianov A.A. The protective effect of intercerebroventricular administration of A-Agonists with complete cerebral ischemia // Bulletin of Experimental Biology and Medicine, 1994, No. 6, p.622-624 /. The study of functional mobility (lability) of the elements of the nervous tissue / Sologub M.I. Functional characteristics of cells during their hyperpolarization and depolarization // Physiological mechanisms of the main nervous processes. Proceedings of the Leningrad. about-va naturalist. L., 1985, v. 75, issue 5, pp. 31-40 / showed that an increase in the resting potential (PP) of cells (hyperpolarization) is accompanied by an increase in their functional mobility, i.e. lability. Finally, there is evidence that hyperpolarized neurons generally have higher resistance to adverse factors / Nasonov D.N. Local protoplasm reaction and pervasive arousal. L., 1959 .; Golikov N.V. The problem of local and pervasive excitation in modern neurophysiology // Mechanisms of local reaction and pervasive excitation. L .: Nauka, 1970, p. 5-12 /. The positive biological effect of hyperpolarization can be associated with the mobilization during this period of energy, and, accordingly, homeostatic mechanisms of the cell / Gorban E.I. The relationship of the membrane potential of adrenocorticocytes and functional activity of the adrenal glands in adults and old.

With depolarization of PP cells, their lability decreases / Sologub M.I. Functional characteristics of cells during their hyperpolarization and depolarization // Physiological mechanisms of the main nervous processes. Proceedings of the Leningrad. natural islands L., 1985, v. 75, issue 5, pp. 31-40., Golikov N.V. Physiological lability and its changes in the main nervous processes. L., 1950, 240 pp. /. At the same time, with stable depolarization of cells, a whole series of pathogenetic processes develop in them: Ca ²⁺ ion input, activation of lipid peroxidation / Dupin AM, Barskov IV, Viktorov IV, Erin AN The level of lipid peroxidation in the focus of compression ischemia of the rat cerebral mohag cortex // Bulletin of Experimental Biology and Medicine, 1994, No. 12, pp. 589-590. Golubev A.G. Nitric oxide (NO) in the central nervous system // Bulletin of experimental biology and medicine, 1994, No. 2, p.201 /, violation of energy metabolism / Gayevskaya M.S. Carbohydrate metabolism of the brain and its relationship with the functional state of the central nervous system during the extinction and restoration of vital functions of the body // Biochemistry; Shapot BC, Gromova K.G. Energy metabolism of the brain and the problem of the nervous system, Kiev: Publishing House of the Academy of Sciences of Ukraine Ukr SSR, 1954, p.151-161; Mac-Ilvein G. Biochemistry and central nervous system. M .: Publishing house of foreign countries. literature, 1962 /, leading ultimately to cell death / Isaev N.K., Zorov DB, Lyzhin A.A. and other Glutamate causes a decrease in the membrane potential of mitochondria in cultured cereal cereal cells // Bulletin of Experimental Biology and Medicine, 1994, No. 2, p.208; Glushkov S.I., et al. Acute poisoning. M .: Medicine, 1989, 432 p .; Puzyrev V.P., Golubenke N.V., Freidin M.B. The competence of mitochondrial genetics // Vestnik RAMS, 2001, No. 10, p.31-37; Kristian T., Siesjo BK Calcium in ischemic cell death // Stroke, 1998, v.29, 3, p.705-718, Mattson MP, Culmsee C., Yu ZF Apoptotic and antiapoptotuc mechanisms in stroke // Cell Tissue Res. , 2000, v. 301, 1, p. 173-187 /.

Thus, at present, there is every reason to say that an increase in PP (hyperpolarization) is accompanied by the development of good metabolic and FS, while a decrease in PP (stable (stationary) depolarization) is accompanied by the development of poor metabolic and PS of nerve cells.

In order to evaluate the functional and metabolic state of the nervous tissue, in our method, an investigation of SCP and EEG was carried out with intracerebroventricular administration of cyclopentyladenosine (CPA). Figure 1 shows the change in SCP and EEG in rats (n = 10) after intracerebroventricular administration of CPA in the neocortex. It is seen that the injection of CPA caused a positive deviation of AMR with primary activation of the power of most (delta-1, delta-2 and beta) EEG rhythms, which then (after 5-10 minutes) gave way to their depression (see table).

Table. EEG rhythm power (μV) of different ranges before and after CPA injection Delta 1 Delta 2 Theta Alpha Beta Before CPA 174.7 ± 14.6 113.4 ± 9.07 77.6 ± 9.15 35.7 ± 4.3 7.34 ± 0.84 4 min after administration 343.4 ± 29.4 *** 137.5 ± 12.2 * 60.97 ± 5.66 * 30.55 ± 2.5 12.00 ± 1.11 *** 16 min after administration 178.7 ± 21.9 75.6 ± 8.63 *** 45.1 ± 5.8 *** 19.92 ± 2.3 *** 4.61 ± 0.49 ***

Asterisks indicate rhythm amplitude values that are significantly different from the period preceding drug administration: * -p <.05, ** - p <.01, *** - p <.001.

On average, the positive deviation of the SCP after 4 minutes after the introduction of the CPA was 6890 ± 2418 μV.

40 minutes after CPA injection, the power of EEG rhythms decreased by 34.56 ± 1.96% (p <0.001). The decrease in EEG power against the background of CPA was approximately the same for all rhythms and ranged from 32.77 ± 5.37% (for alpha) to 37.19 ± 2.64% (for beta rhythm).

Thus, the introduction of CPA over time caused multidirectional changes in the power of EEG rhythms against the background of a positive deviation from AMR. Immediately after administration of the drug, the rhythm power increased, and then, after 5-10 minutes, its inhibition occurred.

According to the literature / Kostopoulos G.K., Phillis J.W. Purinergic depression of neurons in different areas of the rat brain // Exp. Neurol. 1977. Vol. 55. P.719-724, Shefner S.A. Chiui R.H. Adenosine inhibits locus coereleus neurons: an intracellular study in a rat brain slices preparation // Brain Res. 1986. VoL 366, No. 1-2. P.364-368 /, adenosine and its analogues (which includes CPA) inhibit the impulse activity of neurons and cause membrane hyperpolarization. The positivization of SCP, obtained in our experiment, also indicates the hyperpolarization of neurons. The fact that hyperpolarizing effects increase the resistance of nerve cells to the action of adverse factors / Samushiya O.Sh. Ultrastructural manifestations of the treatment effect of ischemic brain damage with sodium oxybutyrate // Questions of modern neurology. Collection of scientific papers. Tbilisi, 1985, p. 184-190; Kulinsky V.I., Usov L.A., Sufianova G.Z., Sufianov A.A. The protective effect of intercerebroventricular administration of A-Agonists with complete cerebral ischemia // Bulletin of Experimental Biology and Medicine, 1994, No. 6, p.622-624; Nasonov D.N. Local protoplasm reaction and pervasive arousal. L., 1959 /, as well as increasing their lability, allows us to say that under the action of adenosine a good metabolic and FS developed in the nervous tissue. However, hyperpolarization could be combined both with an increase in the power of rhythms and its inhibition. The primary activation of the EEG in the delta and beta ranges (Fig. 1) with a positive shift in SCP indicates, most likely, the development of a good functional state similar to anodic exaltation with some increase in metabolic demand against the background of maintaining ionic homeostasis, which gradually changes to complete hyperpolarization inhibition and development of an even better (superior) metabolic and FS. The inhibition of rhythm power that developed after the introduction of CPA was stable and took place over 60 minutes of observation.

Figure 2 shows the change in recorded biopotentials with intraperitoneal administration to rats (n = 22) of ethaminal sodium (nembutal). It can be seen that initially, after the injection of the drug, a negative deviation of SCP (p <0.001) and an increase in EEG power (p <0.001) were observed. Potential negativization averaged 638.8 ± 124.1 μV, and the increase in rhythm power was 28.0 ± 2.3%. After 1-2 minutes, a positive shift in constant potential appeared while maintaining increased rhythm power (Fig. 2, A), while the animal was in a drowsy state. The loss of pain sensitivity and falling asleep of the animal occurred against the background of further positivization of SCP, while reducing the amplitude of the EEG rhythms, the inhibition of which reached a maximum with deepening sleep. The average value of the positive potential shift in etaminal sleep was 1043 ± 283 μV. The nature of the change in the ranges of EEG rhythms during anesthesia did not differ significantly from each other.

In general, the results of the latest study showed that a complex picture of the relationship between SCP and EEG rhythms, revealed on the model of intracerebroventricular administration of CPA, is also observed after intraperitoneal injection of nembutal. The pre-sleep state (drowsiness) was combined with a positive deviation of the SCP and a relatively high power of the EEG rhythms, while falling asleep was accompanied by an even greater positivity of the SCP, which, however, combined with a decrease in the power of the EEG rhythms. The data obtained indicate the formation of hyperpolarization processes in the brain tissue under the influence of Nembutal. The nature of the changes in the recorded indicators suggests that Nembutal, like CPA, causes the development of a generally good metabolic and FS of the nervous tissue of the brain. Common shifts of AMR and EEG also allow you to see the dynamics of this state and the development of excellent metabolic and FS during the transition from nap to sleep.

This study also revealed the period when a negative shift in SCP was observed, combined with a high power of EEG rhythms. These changes in biopotentials were observed immediately after intraperitoneal injection of nembutal. It is obvious that the procedure of administering anesthesia (fixing the animal in the hands, piercing the skin with an injection needle and administering the drug) strongly motivated the animals, and the rats were very excited for the first 1-2 minutes. In this state, there was a negative SCP and an increase in the power of EEG rhythms. The nature of the changes in these biopotentials suggests that depolarization processes, combined with high neuronal activity, develop in the nervous tissue of the cerebral cortex at this time. state type of cathodic exaltation. In a similar state, a decrease in the content of macroergs is recorded in the nervous tissue, and in general, the metabolic state of the nerve cells is similar to that which develops during hypoxia. In addition, the stable depolarization of PP cells activates a whole cascade of intracellular pathogenetic processes / Isaev N.K., Zorov DB, Lyzhin A.A. Glutamate causes a decrease in the membrane potential of mitochondria in cultured cereal cereal grains // Bulletin of Experimental Biology and Medicine, 1994, No. 2, p.208, Dupin AM, Barskov IV, Viktorov IV, Erin A.N. The level of lipid peroxidation in the focus of compression ischemia of the cerebral cortex of rats // Bulletin of Experimental Biology and Medicine, 1994, No. 12, p. 589-590, Puzyrev VP, Golubenko NV, Freidin MB The scope of competence of mitochondrial genetics // Vestnik RAMS, 2001, No. 10, p.31-37 .; Kristian T., Siesjo B.K. Calcium in ischemic cell death // Stroke, 1998, v.29, 3, p.705-718; Mattson M.P., Culmsee C., Yu Z.F. Apoptotic and antiapoptotuc mechanisms in stroke // Cell Tissue Res., 2000, v. 301, 1, p. 173-187 et al. /. The fact of decrease in depolarized neurons of lability / Sologub M.I. Functional characteristics of cells during their hyperpolarization and depolarization // Physiological mechanisms of the main nervous processes. Proceedings of the Leningrad. about-va naturalist. L., 1985, v.75, issue 5, pp.31-40 / also suggests that the stable depolarization of the membrane potential reflects the development of relatively poor metabolic and PS nerve cells.

Figure 3 and 3A shows friendly changes in SCP and EEG when modeling brain ischemia of different severity in rats. Ischemia modeling was carried out in two ways on the same rats sequentially during one experiment. Previously, 2-3 days before the experiment, outbred white rats weighing 150-200 g of both sexes (n = 12) under nembutal anesthesia under the bones of the skull above the frontal cortex of the right and left hemispheres, silver chloride electrodes were implanted. An indifferent silver chlorinated electrode was placed in the bones above the frontal sinuses. Electrode leads were attached to the skull with quick-hardening plastic.

The first model of ischemia ("Ischemia-1") consisted in bandaging both common carotid arteries. The duration of the isolated action of this model of ischemia was 20 minutes, after which an additional administration of the occluder to the middle cerebral artery (CMA) of the left hemisphere (Ischemia-2) was carried out / Sufianova GZ, Usov LA, Sufianov A.A ., Shapkin A.G., Raevskaya L.Yu., Golubev S.S., Murik S.E. A minimally invasive model of focal cerebral ischemia in rats // Experimental and Clinical Pharmacology. 2001, t. 64, No. 4, p. 63-67 /. Combined modeling of two types of circulatory ischemia was carried out for 60 minutes, after which the occluder was removed and SCP and EEG were recorded for another 16 minutes.

Figure 3 and 3A shows the change in the power of the EEG and SCP during modeling of ischemia in two ways. It can be seen that ligation of the common carotid arteries (Ischemia 1) led to an increase in EEG power in the frontal and parietal cortex of the right and left hemispheres. The increase in the power of the rhythm spectrum in all leads as a whole for the entire sample of rats was 14.04 ± 1.75% (p <0.001). The largest increase in amplitude (20.04 ± 3.2%) was observed in the alpha range, where it increased from 23.71 ± 0.86 to 28.46 ± 1.09 μV (p <0.001). For the theta rhythm, the increase was 16.31 ± 3.15%, and it changed from 46.52 ± 2.03 to 54.01 ± 2.08 μV (p <0.01). The increase in the amplitude of the delta rhythm was 10.61 ± 2.79%: from 106.85 ± 3.96 to 118.38 ± 3.74 μV (p <0.01). The beta rhythm has changed the least. Its power increased only by 9.21 ± 4.33% from 7.31 ± 0.34 to 7.98 ± 0.33 μV. Nevertheless, this increase was statistically significant (paired Student's t-test showed differences at p <0.01). Simultaneously with an increase in the power of EEG rhythms, a slight negative deviation of the SCP was observed, which by the end of the period was 1222.51 ± 290.1 μV (p <0.01).

The nature of changes in SCP and EEG during Ischemia-1 modeling indicates that depolarization processes combined with neuronal activation develop in the nervous tissue, i.e. condition type catholic exaltation.

The additional introduction of the occluder in the left hemisphere SMA against the background of the development of general inhibition of EEG rhythms led to more significant changes in the SCP in the neocortex, which had both a positive and a negative orientation (Figure 3, "Ischemia-2"). In the left hemisphere, both in the frontal and parietal cortex, a significant negative deviation of the SCP was observed, which amounted to 20929 ± 8177 and 12880 ± 4175 μV, respectively. In some cases, in the frontal cortex, negativeization reached about 40 mV.

The average inhibition of EEG rhythms in the left hemisphere as a whole in the sample amounted to 25.62 ± 2.41 in the frontal cortex and 22.74 ± 1.94% in the parietal cortex. Most of all, the changes affected the slow frequencies. In the right hemisphere, the inhibition of rhythms was significantly less than in the left hemisphere, and amounted to 14.28 ± 2.49% for the frontal cortex and 13.03 ± 2.19 for the parietal. Analysis of changes in the EEG in the right hemisphere, separately for frequencies, that inhibition affected only the delta rhythm. In the remaining frequency ranges, the introduction of the occluder into the left hemisphere SMA did not lead to significant changes in rhythms compared with the period preceding brain ischemia. Differences in changes in biopotentials in the right hemisphere also affected SCP. In the parietal cortex of the right hemisphere, the negative deviation was almost 3 times less than in the left hemisphere and amounted to 7705 ± 1373 μV. In the frontal cortex of the right hemisphere, the deviation of the constant potential was generally positive and equaled 6183 ± 2605 μV.

Thus, the development of circulatory ischemia, according to model 1, was accompanied by a relatively small negative deviation of SCP and an increase in the power of EEG rhythms in all leads. The use, in model 2, of the left hemisphere SMA occlusion led to additional significant negation of the left hemisphere SCP and inhibition of EEG in this, against this background.

The nature of the change in the recorded potentials in the left hemisphere after the introduction of the occluder into the left hemisphere SMA indicates the development of strong depolarization processes in the neocortex, combined with inhibition of neuronal activity. In other words, a condition such as parabiosis or Catholic depression Verigo develops in the nervous tissue of the left hemisphere at this time. The metabolic and FS neurons accompanying this phenomenon are obviously even worse than with Ischemia-1.

The changes in the EEG and SCP observed in the right hemisphere during Ischemia-2 are most likely associated with the redistribution of blood flow due to the activation of collateral circulation mechanisms. In the literature there is evidence of an increase in blood flow in the pool of symmetrical arteries of the opposite hemisphere stroke. The positive shifts of SCP in the frontal cortex of the right hemisphere, which we observed simultaneously with the negation of potential in the left hemisphere, indicate an increase in blood flow in this part of the brain and the development of repolarization processes in it, and a decrease in the power of EEG rhythms reflects an improvement in the metabolic and functional state of the nervous tissue, worsened during " Ischemia 1 ". In other words, in the frontal cortex of the right hemisphere, after the introduction of the occluder, it seems that a state close to preoperative was formed. This is evidenced by the histological analysis of the state of the nervous tissue of the right hemisphere / Sufianova GZ, Usov L.A., Sufianov A.A., Shapkin A.G., Raevskaya L.Yu., Golubev S.S., Murik S .E. A minimally invasive model of focal cerebral ischemia in rats // Experimental and Clinical Pharmacology. 2001, t. 64, No. 4, p. 63-67 /. Due to increased blood supply to the frontal cortex of the right hemisphere, most likely, there was a partial "robbery" of the parietal cortex of the same hemisphere. A negative shift in the SCP in the parietal cortex of the right hemisphere, together with a slight decrease in the rhythm power in it, indicates that a relatively unfavorable metabolic and functional state also formed here in the period of Ischemia-2.

Figures 3 and 3a also show that after the occluder was removed in the leads, as a rule, changes in the constant potential were recorded, opposite to those that occurred when it was introduced into the MCA. On average, over the entire group, in the left hemisphere in the frontal and parietal cortex for a period of 16 minutes, the potential positively increased by 42.7 ± 10% (P <0.05) and 40.0 ± 22% (P <0.05), respectively . In the right hemisphere in the frontal cortex, occluder extraction caused a decrease in constant potential by 23.8 ± 12.7% (P <0.05). In the parietal cortex of the same hemisphere, a slight positivization of SCP was observed, equal to 17.2 ± 11.2%.

An analysis of the rhythm changes that occurred in this case showed that reperfusion led to an increase in EEG power in all channels and all frequencies by an average of 11.6 ± 2.03% (p <0.001). Comparison of EEG changes in the right and left hemispheres revealed an increase in rhythm power mainly in the parietal cortex of the right and frontal cortex of the left hemisphere. The largest increase in the average amplitude of all rhythms was observed in the parietal cortex of the right hemisphere and amounted to 29.08 ± 2.86% (p <0.001), while the increase most affected the alpha and beta ranges (respectively, 31.47 ± 5.14% (p <0.002) and 36.13 ± 9.3% (p <0.004) versus 20.25 ± 3.05% (p <0.01) for delta and 18.98 ± 2.86% (p < 0.01) for theta rhythms).

The increase in rhythm power in the frontal cortex of the left hemisphere was 16.59 ± 2.89% (p <0.001) without a clear predominance in any of the ranges. In the frontal cortex of the right hemisphere, there was only a tendency to increase the amplitude in the theta rhythm region. In the parietal cortex of the left hemisphere, against the background of increased activity in the corresponding region of the right hemisphere, no significant changes were found in any frequency.

Thus, according to EEG data, reperfusion changes affected mainly the parietal cortex of the right hemisphere, in which the power of all rhythms increased. In the left hemisphere, a slight increase in the amplitude of the rhythms was observed in the frontal cortex. Comparison of the EEG established within 16 min after reperfusion with the EEG observed in these animals before and during Ischemia 1 showed that the right hemisphere was closer to the Ischemia I period in characterizing the basic rhythms, although the amplitude was slightly lower . In the left hemisphere as a whole, the rhythm power, as well as during ischemia, remained on average lower, even compared with the preoperative period, by 18.89 ± 2.63% (p <0.001).

Thus, extraction of the occluder and reperfusion of the brain by MCA as a whole caused an increase in the power of EEG rhythms in all leads. In the frontal and parietal cortex of the left hemisphere and the parietal cortex of the right hemisphere, a positive deviation of SCP was observed. In the frontal cortex of the right hemisphere, reperfusion of the SMA of the left hemisphere led to an increase in EEG power against the background of negative SCP. In other words, the restoration of the blood flow regime corresponding to the period of "Ischemia-1" in the left hemisphere according to electrophysiological data, reflected a way out of the parabiotic state, that is, an improvement in the metabolic and functional state of the nervous tissue. Similar processes took place in the parietal cortex of the right hemisphere, while occluder extraction in the frontal cortex, reducing collateral blood supply, apparently worsened its metabolic state, which activated it again (as in the simulation of Ischemia-1).

Reperfusion data indicate that brain activation observed by EEG is possible against a background of both negative and positive abnormalities of SCP. If in the first case this indicates a deterioration of the functional and metabolic state (as well as with "Ischemia-1"), then in the second case it indicates an improvement in connection with the exit from the state of cathodic depression with increased blood flow.

An analysis of the literature data and the nature of the changes in the complex of bioelectric indicators (EEG and SCP) obtained in our experiments with ischemia allows us to draw a conclusion about the functional and metabolic processes in the nervous tissue of the brain that accompany these changes:

- negative changes in SCP and an increase in EEG power occur during depolarization of the membrane of neurons, accompanied by an increase in excitability and reflect the development of poor metabolic and FS nervous tissue;

- negative shifts in SCP and inhibition of EEG power occur with even greater depolarization of neurons, the development of depolarization inhibition (parabiotic or Catholic type) and reflect the development of even worse metabolic and FS of the nervous tissue;

- reverse changes in SCP and EEG power reflect an improvement in the functional and metabolic state of the nervous tissue of the brain.

The results of the presented experiments demonstrated high diagnostic capabilities of the proposed method. According to bioelectric activity data, our method for the first time allowed to differentiate from a qualitative point of view the change in metabolic and FS of the nervous tissue of the brain under the influence of CPA, Nembutal and ischemia of different severity on the brain. This method can be used not only to identify the specific effects of drugs and various environmental conditions on brain cells, but also the role of changes in metabolic and FS of nerve cells in the mechanism of various mental phenomena, in particular, in motivational-emotional reactions. The proposed method allows to register and differentiate the transition of one functional and metabolic state to another, thereby increasing the accuracy of diagnosis of pathological and normal conditions.

Thus, the proposed method makes it possible, on the basis of a qualitative analysis, to accurately determine the current functional and metabolic state of nerve tissue and to adequately differentiate physiological and pathological phenomena in the brain, and also allows the development of new neuroprotective drugs and to study the mechanisms of pathological and physiological conditions in the experiment.

Claims (1)

A method for determining the functional and metabolic state of nerve tissue, including simultaneous recording of an electroencephalogram (EEG) and constant potential level (SCP), comparing them and determining the functional and metabolic state of nerve tissue by the nature of changes in the measured parameters over the same period of time, characterized in that with negative SCP and increasing the power of the EEG accompanying the depolarization activation of neurons, the development of poor metabolic and functional thawing (PS) of nerve cells, with negative SCP and a decrease in EEG power accompanying depolarization inhibition of neurons, determine the development of an even worse metabolic and FS, with positive CT and increase in EEG power accompanying repolarization activation of neurons after depolarization inhibition, or hyperpolarization activation, determine the development of good metabolic and FS of the nervous tissue, and with positivization of SCP and a decrease in the power of the EEG, accompanying either repolarization inhibition of neurons after depolarization activation, or hyperpolarization inhibition, they determine the development of very good metabolic and PS cells of the nervous tissue.

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