[Acute period in a rat model of brain trauma: immediate seizures, damage to functional neocortical zones and behavioral disturbances]. / Ostryi period pri modelirovanii cherepno-mozgovoi travmy u krys: nemedlennye sudorogi, povrezhdenie funktsional'nykh zon novoi kory i narusheniia povedeniia.

BACKGROUND: Establishing the relationship between the damage in the neocortex and the functional manifestations of these lesions is important to understand the mechanisms of acute seizures and their consequences. An analysis of immediate seizures in patients with a traumatic brain injury (TBI) in practice is difficult, however it can be performed in animal models. AIM: To compare the damage to functional neocortical areas with the semiology of immediate seizures and behavioral disturbances in the acute period after lateral fluid percussion (TBI model) in rats. MATERIAL AND METHODS: The study was performed on 48 Wistar rats. TBI was modelled using lateral fluid-percussion injury to the right sensory-motor cortex. To study the semiology of immediate seizures, video recording was performed at the moment of the injury and 5 min after it. After that, a number of behavioral tests were employed. RESULTS AND CONCLUSION: This study presents the first detailed evaluation of damage to the functional neocortical areas in the acute period of TBI using the 'unfolded maps' approach. The focus of damage in the cortex increased from 3rd to 7th day and demonstrated a complex shape, extending far beyond the area of the direct impact. TBI induced immediate seizures with a variability which cannot be explained by the involvement of certain areas of the neocortex alone, as well as behavioral disturbances suggested to reflect developing necrosis predominantly in the sensory area of the neocortex.

[Early electrophysiological consequences of dosed traumatic-brain injury in rats]. / Rannie élektrofiziologicheskie posledstviia dozirovannoi cherepno-mozgovoi travmy u krys.

AIM: To analyze the pathological electrical activity during the acute period after traumatic brain injury (TBI) and to search for potential morphological correlates of this activity in the neocortex and hippocampus. MATERIAL AND METHODS: The study was performed on male Sprague Dawley rats. TBI was modeled using a lateral hydrodynamic impact in the sensorimotor cortex area. ECoG was continuously recorded one week before and one week after TBI. A histological analysis was performed one week after TBI. Brain slices were Nissl stained as well as immunohistochemically stained for astrocytes (GFAP) and microglia (Isolectin B4). The damage to the neocortex and hippocampus was evaluated. RESULTS AND CONCLUSION: The slowdown of the background activity one and six hours after TBI and appearance of epileptiform activity in a half of animals one week after TBI were shown. The number of discharges was correlated with the area of astrocyte gliosis in the neocortex and with the number of dark (ischemic-like) neurons in the hippocampus. Microglial activation did not correlate with the epileptiform activity. These data are important to understanding early mechanisms of post-trauma epileptogenesis.

[The Effects of Chronic Combined Stress: Changes in Behavior of Rats with Various Responses to Novelty].

We studied the effect of chronic combined stress (model of experimental neurosis) on behavior of rats with different basal strategies of behavior in novelty conditions. Chronic stress resulted in decreases in the body weight and testosterone contents in the blood and neocortex in all animals. Animals with initially low orient- ing-exploratory response in the "open field" test did not exhibit substantial alterations of behavior during repeated testing in this test of the "dark-light chamber" test; however, the depression-like behavior was more expressed in the second forced swim test. Chronic combined stress did not significantly affect the behavior of this group of rats. Animals with initially high orienting-exploratory response in the "open field" test exhibited decreased locomotor and exploratory activity in the repeated "open field" tests. The decreases in the locomotor and exploratory activity were substantially less expressed in the repeated tests in these rats after chronic combined stress. The indices of depression-like behavior increased one month after the end of exposure to chronic combined stress. Our data demonstrate that different responses to novelty in the "open field" test do not allow predict with reasonable certainty the development of depression-like behavior after exposure to chronic combined stress.

[CHANGES OF THE CEREBRAL CORTEX AFTER DOSED TRAUMATIC BRAIN INJURY IN RATS OF DIFFERENT AGES].

Using dosed lateral fluid percussion, moderate and severe traumatic brain injury (TBI) was modeled in one- and two-year-old rats. Brain sections were stained using the Nissl cresyl violet method and an immunohistochemical reaction was performed for the demonstration of glial fibrillary acidic protein (GFAP), a marker of astrocytes. The results obtained indicate the formation in the cerebral cortex, ipsilateral to the impact, the zones of direct and remote of injury. The zone of direct injury corresponded to the area of immediate contact of the liquid column with the dura mater, whereas the remote area of damage was located laterally and caudally to the former. Morphological signs of the injury depended on the force of impact and were manifested in both age groups by astrocytic gliosis and the thinning of layer I of the cortex resulting from neuronal death. The emergence of ischemia-modified neurons, probably, was due to a local disruption of the blood supply. Disorders in the brain in one-year-old rats had a local character and those in two-year-old rats were diffuse, while gliosis was inhomogeneous. The reproducibility and adequacy of the model allow its use for research of molecular-genetic mechanisms of TBI outcomes in humans, as well as for the identification of common mechanisms of TBI consequences and the pathogenesis of the major diseases, comorbid with TBI, primarily depression and epilepsy.

[Functional effects of transcranial electromagnetic stimulation (60 and 70 Hz) of the brain of intact rats and rats with acute brainstem damage].

Behavior and brain electrical activity of 79 male Wistar rats (intact and with acute experimental brainstem injury) were studied during the course of therapeutic transcranial electromagnetic stimulation (TEMS) with frequencies 60 and 70 Hz. In intact animals this effect was accompanied by a decrease in voluntary motor activity and increase in synchronization of the brain electrical activity, in particular, in the delta and beta1 frequency ranges. This inhibitory effect was similar to that of sleep. In the early period of acute experimental stem pathology, the TEMS course was accompanied by suppression of EEG signs of adaptive post-operative stress response and could lead to increased severity of the condition of an animal, along with the slowing of postoperative recovery. Cytomorphological evidence was obtained to the importance of vascular factor in the formation of cerebral reactions to TEMS.

[Remote control of the goal-directed behavior of freely moving rats by telestimulation of the rewarding brain structures].

The procedures are described that make it possible to train laboratory rats for remote control of their goal-directed behavior in open environments by telestimulation of rewarding brain structures. Rats were implanted electrodes in the lateral hypothalamus and lateral preoptic area. A week after surgery, rats were placed in an operant chamber and given electrical stimulation of increasing/decreasing intensity to each location to determine the most suitable site/hemisphere for reward delivery as well as the optimal stimulation parameters and the thresholds of behavioral reactions elicited. Then in T-maze, the animals were trained to obtain rewarding brain stimulation by running forward and turning correctly to the left or right arm of the maze in response to corresponding left- or right-turning light signal. At the last stage, rats were worn a backpack containing receiver-based remote-controlled microstimulator, connected to the implanted brain electrodes, and the animals were placed in open environments. The rewarding brain stimulation was delivered remotely using a transmitter connected to a laptop PC. Rats moved forward performing 'scanning' left-right head movements. Head movement in a desirable for the experimenter direction was reinforced. Animals remotely controlled by electrical stimulation of rewarding brain structures moved from one place of the environment to another according to any route given by an experimenter, overcame obstacles of different difficulties, not reacting to bright illumination, sounds and other external stimuli, and not exhibiting fear or curiosity, which are the typical reactions to novel surroundings. The more difficult was an obstacle the more stimulation was required to force an animal to overcome it.

[Study of the role of the right and left orbitofrontal cortex in compensatory cerebral reactions after acute brainstem damage].

Significance of the right and left orbitofrontal cortex (OFC) in recovery after acute brainstem lesion (at the level of n. Deiters) was investigated using rat model of complex brainstem-orbitofrontal cerebral damage. It was found that the right-side lesion of the OFC combined with isolated brainstem damage resulted in aggravation of the animal condition and highly probable lethal outcome within the first two weeks after surgery (because of the brain circulation disorder of hemorrhagic type). It may be associated with sympathetic activation. It is suggested that a certain "stimulation" of the left OFC (as the effect of its incomplete destruction) involves a parasympathetic compensatory reaction that allows animals with a severe brainstem pathology to survive. It is shown that, with the general nonspecific tendency to postoperative increase in emotionality, the greatest shifts in the emotional sphere take place under conditions of a combined damage of the brainstem and left OFC.

Changes in spontaneous brain bioelectrical activity during transcranial electrical and electromagnetic stimulation.

The systems responses of the brain to therapeutic transcranial electrical and electromagnetic stimulation were studied and the neurophysiological criteria for assessing the efficacy of this treatment were identified using comparative clinical and experimental studies with analysis of spontaneous bioelectrical activity, along with assessment of behavioral and clinical measures. Study groups consisted of six patients with chronic post-traumatic unconscious states during courses of transcranial electrical stimulation and 17 intact Wistar rats subjected to transcranial electromagnetic stimulation. A relationship was found between the effects of transcranial stimulation and the initial level of intercenter interactions of brain bioelectrical activity assessed in terms of coherence. Hypersynchronization of biopotentials, identified as a major element in the reactivity to this type of stimulation, may be of the greatest value in the recovery of patients with cerebral pathology in cases with initially reduced levels of intercenter interactions in the absence of pathologically increased functional connections in the brain.

[Changes in the brain spontaneous bioelectrical activity during transcranial electrical and electromagnetic stimulation].

In order to study systemic brain reactions on transcranial electrical or electromagnetic medical stimulation and specify the neurophysiological criteria of its efficiency, comparative clinical and experimental examination was performed with the analysis of spontaneous bioelectric activity and behavioral or clinical parameters. We examined 6 patients with prolonged posttraumatic unconsciousness states treated with electrical stimulation and 17 intact Wistar rats subjected to electromagnetic stimulation of the brain. The effect of the transcranial stimulation was shown to depend on the initial level of the intercentral interactions of brain bioelectrical activity, estimated by the EEG coherence. Hypersynchronization of biopotentials as the main element of the brain reactivity can be the most useful for the rehabilitation of patients with cerebral pathology in cases of initially lowered level of the intercentral interactions in the absence of pathologically strengthened functional connections.

[Selection of behavioral test parameters for estimation of typological features of rat behavior]. / Vybor pokazatelei povedencheskikh testov dlia otsenki tipologicheskikh osobennostei povedeniia krys.

Behavior of 86 rats was examined in three behavioral tests, i.e., open field, forced swimming and emotionality by F. King. The results of statistical analysis of all the indices obtained with application of factor analysis suggest that the three tests characterize four relatively independent behavioral components: emotionality, locomotor-exploratory activity, olfactory performance, and resistance to adverse emotional factors. A contribution of each measured parameter to the above components was estimated. Such an approach makes it possible to reasonably select most important behavioral features when estimating locomotor activity and emotionality of animals.

Monitoring of the oxidation-reduction state of brain structures in freely moving rats during sleep-waking cycles by potentiometric recording.

Freely mobile mongrel male rats weighing 300-350 g were used for studies of changes in the oxidative-reductive (redox) state of brain tissue during cycles of waking, slow-wave sleep, and paradoxical sleep, by recording the potential of the oxidative-reductive state of brain tissue with platinum electrodes implanted into the cerebral cortex ad hippocampus. Electromyograms were also recorded from the cervical muscles, and overall movement activity was also recorded. A common platinum reference electrode was implanted into the nasal bones. These experiments showed that in rats, episodes of waking and paradoxical sleep occurred on the background of increases in the oxidation-reduction potential state of brain tissue at a series of brain points, which we termed "metabolically active." Transitions from waking and paradoxical sleep to slow-wave sleep were accompanied by decreases in the potential of the redox state. The magnitude of changes in the tissue redox state varied up to 100 mV. It is suggested that transitions from waking and paradoxical sleep to slow-wave sleep are accompanied by dynamic changes in the balance of brain tissue energy metabolism between the main energy sources. Oxidative phosphorylation dominates in waking and paradoxical sleep, while aerobic glycolysis dominates slow-wave sleep. We suggest that this latter should be interpreted as a decrease in the potential of the tissue redox state and the formation within the tissue of oscillations during slow-wave sleep. Formation of oscillations is typical for acceleration of glycolytic processes. Recently published data suggest that the major compartment or aerobic glycolysis is the astroglia.

[Rat brain reactions to acute brain stem lesion on dynamics of parameters of cerebral electric activity]. / Reaktsiia mozga krys na ostroe stvolovoe povrezhdenie v dinamike pokazatelei tserebral'noi élektricheskoi aktivnosti.

Despite an old history of a question, adaptive brain reactions that develop after an acute brainstem lesion have not been adequately investigated. With the aim to study the central mechanisms of compensation/decompensation and to specify the character of involvement of orbitofrontal cortex and hippocampus into these processes the spatiotemporal organization of brain electric activity was analyzed in 8 rats before and after electrolytic brainstem lesion at the level of the lateral vestibular nucleus Deiters (VND). The electric activity was recorded from symmetric frontal and somatosensory cortical areas, hippocampal areas CA1, and intact VND. Spectralcoherent analysis showed that adaptive reactions are most clearly manifested by changes in the spatiotemporal organization of the theata activity: 1) early brainstemhippocampal synchronization of the electric activity in the frequency range of 6-7 Hz with subsequent involvement of anterior cortical regions is characteristic of survived animals; 2) independent hippocampal-cortical hemispheric system of excitation in the frequency of 4-5 Hz precedes the fatal outcome. On the day before the fatal outcome the interhemispheric coherence in the orbitofrontal cortex dropped, which suggests the involvement of these brain regions into the processes of visceral regulation.

[Potentiometric monitoring of the redox state of brain structures of freely-moving rats in sleep-wake cycles]. / Monitoring okislitel'no-vosstanovitel'nogo sostoianiia struktur golovnogo mozga svobodno-podvizhnoi krysy v tsiklakh bodrstvovanie-son putem potentsiometricheskoi registratsii.

Variations of brain tissue redox state potential (E) of freely-moving white rats (300-350 g) in cycles of wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) were measured by platinum electrodes symmetrically implanted into the frontal and occipital cortices and hippocampus. In addition, EMG of neck muscles and general motor activity of animals were recorded. The common reference electrode was implanted in the nasal bone. It was shown that in some brain sites (called active), episodes of W and PS were accompanied by a rise of E, and during transitions from W and PS to SWS, E dropped. The value of E varied in the range of 100 mV. It is suggested that transitions from W and PS to SWS are accompanied by shifts in the balance between the main energy sources. Oxidative phosphorylation prevails in W and PS, whereas aerobic glycolysis is the main source of energy during SWS. We think that this suggestion is supported both by a decrease in E in SWS and its oscillations typical of glucolytic processes [Aon et al., 1992]. Recent literature data [Bitter et al., 1996] suggest that astroglia is the main compartment for aerobic glycolysis.

Changes in redox potential in rat brain tissue developing during episodes of paradoxical sleep.

Paradoxical sleep is regarded by many authors as consisting of episodes of integrative brain activity, this view being based on data relating to changes in overall brain electrical activity (depression of electrocorticograms or the appearance in electrocorticograms of oscillations at the theta rhythm) and increases in neuron activity, data showing negative changes in the potential of the direct current, and data demonstrating increases in brain temperature and local brain blood flow, increases in glucose utilization, and increases in the levels of free oxygen in brain tissue. We have previously observed that episodes of paradoxical sleep are accompanied by increases in the redox potential of brain tissue (E) by several millivolts. In these experiments, we used a direct current amplifier with a low input resistance (1 Mohm), which decreased the true magnitudes of changes in E accompanying episodes of paradoxical sleep. One of the aims of the present work was to determine more accurate measures of the functional changes of this type of sleep, by using a direct current amplifier with a high input resistance (1 Gohm). The second aim of the present work was to obtain more accurate data on differences in changes in oxidative metabolism in different parts of the brain during episodes of paradoxical sleep, by making simultaneous recordings of E from two points of the brain, using several different combinations of pairs of points.

[The effects of combined electrolytic brain stem-orbitofrontal and brain stem-hippocampal damages to the rat brain]. / Effekty sochetannogo élektroliyicheskogo stvolovo-orbitofrontal'nogo i stvolovo-gippokampal'nogo povrezhdeniia mozga krys.

Morphofunctional studies of animals with associated electrolytic orbitofrontal and hippocampal brainstem lesions as compared to variants of isolated brainstem coagulation showed participation and specific role of orbitofrontal cortex and hippocampus in adaptive-compensatory brain reactions of rats with brainstem lesions. Associated brainstem-orbitofrontal damages result in aggravation of the animals' condition and highly probable lethality within the first two weeks after surgery due to blood circulation dysregulation of hemorrhagic type and probably due to secondary hypothalamus dysfunction. Associated brainstem-hippocampal coagulation intensifies primarily brainstem neurologic symptoms and prolongs time of their reverse development, i.e. supports the brainstem centre of stable pathological activity.

[Oscillations in the oxidation-reduction potential of the brain tissue in rats developing during wakefulness and slow-wave sleep]. / Ostsilliatsii v potentsiale okislitel'no-vosstanovitel'nogo sostoianiia tkani golovnogo mozga krysy, razvivaiushchiesia pri bodrstvovanii i medlennom sne.

Variations of the brain cortex redox state potential (E) were recorded in freely moving white rats (mass of 300-350 g) with implanted platinum electrodes (with the platinum reference electrode in the nasal bone) during sleep-wake cycles. It was found that transitions from the slow-wave sleep to wakefulness were accompanied in the number of cortical areas (metabolic-active sites) by the E rise, while the transitions from the wakefulness to slow-ware sleep were associated with a drop of E. However, the episodes of the short-term arousals during the slow-wave sleep were accompanied by the respective decreases in E thus forming the irregular E variations (1.5-3 min in duration). It was also found that the oscillations of a typical pattern (quasisinusoidal with the frequency of 10-20 osc/min and the amplitudes up to several mV) could take place in the metabolic-active cortical sites. These oscillations were defined as fast E oscillations. During the slow-wave sleep, the less regular oscillations with the lower frequency (1.2-10 osc/min) and higher amplitude were recorded in the same cortical sites. These oscillations were defined as slow. It is suggested that the fast metabolic oscillations of wakefulness are mainly controlled by the mitochondria of neuronal populations, whereas the slow metabolic oscillations which occur in the slow-wave sleep are related with glycolysis in populations of glial cells.

[The modelling of the glycolytic oscillations in the potential of the oxidative-reductive status of the brain tissue in waking and anesthetized rats]. / Modelirovanie glikoliticheskikh ostsilliatsii v potentsiale okislitel'no-vosstanovitel'nogo sostoianiia tkani golovnogo mozga bodrstvuiushchikh i narkotizirovannykh krys.

It was found that chemical hypoxia created by intraperitoneal injection of potassium cyanide (5-7 mg/kg) induced in both waking and anaesthetized (pentobarbital, 40 mg/kg) albino rats a significant decrease in the brain redox state potential (E) monitored with platinum electrodes. This decrease could be accompanied by a generation in some brain points of local chains of gradually damped quasisinusoidal E oscillations. Such oscillations were more expressed in waking than in anaesthetized animals. The frequency range of these oscillations was 4-7 cycles/min. This is the range of overlapping frequency ranges characteristic for the high level of vigilance (5-20 cycles/min) and slow-wave sleep and drowsiness (1.5-6 cycles/min). The amplitude of the observed oscillations was close to the maximal amplitude of the brain E oscillations characteristic for the high level of vigilance (up to several mV). The obtained evidence favors our suggestion that behavior-related E oscillations are formed by the oscillations in the redox balance of glycolysis. The similarity of the normal physiological oscillations and those simulated by us under abnormal conditions suggest a certain common mechanism of their generation.

[Local destruction of Deiters' lateral vestibular nucleus (an experimental model of a focal brain stem lesion)]. / Lokal'noe razrushenie lateral'nogo vestibuliarnogo iadra Deistersa (éksperimental'naia model' ochagovogo porazheniia stvola mozga).

The experimental rat model of the local brainstem destruction by isolated electrical coagulation of the lateral vestibular nucleus Deiters was offered for studying the adaptive-compensatory CNS reactions after acute brainstem lesions. Morphological changes and functional derangements were correlated in 22 animals. Neurological disorders and behavioural reactions were reproducible and stable in rats with exact localization of coagulated foci. The results demonstrate the adequacy of the proposed model.

Is the electrical activity of the brain always electrical? (The factors forming the potential of the metallic electrode during its direct contact with the brain).

This article is devoted to an analysis of the factors forming slow changes in the potential of a metallic electrode coming into direct contact with living tissue. Data are presented in this paper according to which, the electrochemical activity of the tissue also participates, in addition to electrical activity, in the formation of the electrode potential. The article is in the nature of a discussion.

[Is the electrical activity of the brain always electrical? (The factors that generate the potential of a metal electrode in direct contact with the brain)]. / Vsegda li élektricheskaia aktivnost' mozga--élektricheskaia? (O faktorakh, obrazuiushchikh potentsial metallicheskogo élektroda pri neposredstvennom ego kontakte s golovnym mozgom).

In the paper are analysed the factors creating slow potential changes of a metal electrode directly contacting with the living tissue. In the paper are presented the data according to which electrochemical tissue activity participates in creating the electrode potential besides the electrical activity. The paper carries a discussion character.