Search

EEG power changes in anaesthetized and conscious rats were studied (under repeated experiments) in wide frequency band (0.1-200 Hz) during cortical spreading depression wave (SD). In anaesthetized rats the decrease of EEG spectral power was shown through all diapasons under consideration. The most pronounced decay of the EEG power was marked in the 30-40 Hz band (27.3 ± 18.5, p = 2.46 x 10-(11)). In other frequency ranges the power decrease was less but its significance remained high. In conscious rats the simultaneous decay of the EEG power from 20 to 100 Hz range was also the most informative index of SD wave. The maximum power loss was found for band 30-40 Hz (11.2 ± 7.8, p = 2.55 x 10(-7)). It was shown that besides of EEG power decay the development of SD wave was characterized by the appearance of high frequency activity in front of SD and at the end of it. The increase of high-frequency activity in front of SD wave appeared in the ipsilateral hemisphere and moved along the cortex with the velocity of the SD wave itself. However the bursts of high frequency activity at the end of unilateral SD occurred simultaneously in both hemispheres and lasted 1.5-2.5 min. Findings contribute to detection of SD wave on basis of EEG spectral analysis.

EEG aftereffects of spreading depression waves were studied in waking rabbits in chronic experiments by spectral coherence analysis. Experiments were divided in two groups: early (from the first to the third-fourth experiments) and late (fifth-tenth experiments). During the early experimental series, unilateral persistent EEG changes consisting in an increase in the delta- and beta-band power with a simultaneous depression of the gamma-band activity were observed in the ipsilateral to SD hemisphere. In addition, interhemispheric coherence between symmetrical cortical points decreased. During the late experimental series, a generalized bilateral increase in the power of the delta and beta activity was demonstrated with a rise in coherence in the beta band. This generalized activity occurred cyclically and was distinct during a long period of time (2-3 hours) after propagation of a single SD wave. Such kind of cyclical activity blocked the propagation of subsequent SD waves in the neocortex of a waking rabbit and decreased the probability of recurrent wave origin up to a complete cessation of wave generation. Thus, a cortical SD wave provoked the appearance of synchronized beta oscillations in the EEG, which in turn actively influenced the properties of recurrent waves.

The EEG spectral analysis applied to electrical brain activity of rabbits in the state of animal hypnosis revealed a 2-4-fold increase in the power of the sigma frequency band (12-17 Hz) and a 1.5-2-fold decrease in the gamma frequency (especially 40-70 Hz) in addition to well-known growth of delta (0.3-3 Hz) and reduction of theta activity (4-8 Hz). The changes were more prominent in the frontal cortex areas. The influence of hypnotic state on cortical gamma activity pharmacologically augmented by ketamine injection was analyzed. Administration of subanesthetic ketamine doses led to behavioral locomotor excitation of an animal accompanied by a long-lasting (up to 2 h) increase in the gamma electrical activity. If the animal hypnosis was induced after the ketamine injection, it resulted in an almost instant reorganization of the spectral power. The slow-wave power increased and the gamma-power decreased to the baseline levels. Thus, the animal hypnosis eliminated the reorganization of cortical rhythmicity produced by ketamine, which suggests a stabilizing and, to a certain extent, protective function of this kind of hypnosis in the states of behavioral locomotion and stress.

It was shown that the manifestation of the SD phenomenon in dynamics of the cortical high-frequency gamma activity is rather prominent after bipolar interpretation of the common reference electrode derivations, i.e. when the modeling of the bipolar signal on the base of monopolar EEG recordings is used. The SD wave was accompanied by significant decrease in the power of the EEG gamma band (37-47 Hz) in all observed cortical areas. A curve of decline of gamma activity power had distinct fore and back fronts, so the time of SD appearance in different cortex areas and it's spread succession could be well determined. In the long-term experiments SD waves were characterized by normal (i.e. successive) spread through the cortex mainly in initial three-four experiments. In the subsequent tests latency of SD waves in different cortex areas changed and disturbance of propagation became obvious. Sometimes SD arose rapidly (due 0.5-2 min) on the whole dorsal neocortical surface, when the standard injection of the KCI was done. In the most of experiments the delay of the SD wave appearance was prolonged till 6-9 min or no SD wave occur at some cortical regions. Week epileptiform activity could conduct abnormalities in the SD. In many instances electrophysiological signs of the cortical excitability changes were absent. However the modified spatial SD characteristic and spontaneous occurrence of the repeated. SD waves indicated the increased functional inhomogeneities of the neighboring cortical areas. So, spectral EEG analysis in awake rabbits made it possible to characterize the SD wave both in case of its normal propagation through the cortex and in unusual forms of this reaction.

A spreading depression (SD) can spontaneously develop in seizures, attacks of migraine, vascular disorders and other pathological states of the brain. However, problems in technique of recording the DC-potential in the neocortex of humans and waking animals substantially restrict the possibilities of studying functional consequences of the SD. In this article, the EEG pattern was studied in detail at the moment of the SD development. Specific features were revealed, which make it possible to detect the SD without recording shifts of the DC-potential. At the moment of the SD arrival, the interhemispheric balance drastically disturbs because of a strong decrease in the high-frequency activity. By the time indices, the course of the suppression of the gammal and gamma2 EEG frequencies is the most reliable symptom of the SD wave development. The EEG spectral power in the delta band increases with a certain delay in reference to the deep depression of the high-frequency activity and is, in essence, an SD aftereffect. The found EEG signs of an SD wave can substantially simplify the identification of this phenomenon both in experiment and clinical conditions in certain pathological states of the brain.

Effects of a single wave of the cortical spreading depression (SD) on the ECoG of a waking rabbit was studied with chronically implanted intracortical calomel and silverball epidural electrodes. DC potential shifts and integral electrical activity were recorded monopolary in reference to a nasal-bone electrode. ECoG spectral analysis (FFT) showed that an SD wave was accompanied by a suppression of the neocortical activity in a broad frequency range (0.25-80 Hz). However, the SD-related ECoG depression was a rather short phenomenon (5-7 min) as compared to a following rebound effect, i.e., persistent (1.5-2 h) unilateral exaltation of bioelectrical activity. The spectral power in the delta (6-14 fold) and beta bands (2-6-fold) increased, whereas the high-frequency activity (40-80 Hz) remained suppressed. Similar changes in the contralateral neocortex were poorly pronounced or absent; this resulted in a strong interhemispheric asymmetry. It is suggested that (1) exaltation of the delta activity after SD wave is related not only to a dendrite swelling and changes in the extracellular space structure but to increase in synaptic transmission efficiency, probably, by the type of anoxic potentiation, (2) activation of some subcortical structures by the mechanism of their release from the inhibitory neocortical control is an additional factor of the augmentation of the delta and spindle-like beta activity after an SD wave, and (3) the long-term attenuation of the high-frequency gamma activity is a result of its strong suppression during the SD and its reciprocal relations with the exalted delta activity.

Cortical negative DC potential shifts were studied on two experimental models: focal cortical ischemia provoked by a photothrombotic occlusion of the distal part of the middle cerebral artery (dMCA) and a combination of systemic hypoxia induced by bilateral ligation of the common carotid arteries (temporary ligation of the left artery and permanent ligation of the right one) with breathing with 0.5% carbon monoxide (CO). The perifocal ischemic depolarization (ID) after the dMCA thrombosis was found to reach 28-33 mV and then gradually decline during 80 min to a certain residual level about 5 mV. Spontaneous depolarization didn't occur during hypoxia but it was easily provoked in one or both hemispheres by the waves of the cortical spreading depression (SD). The amplitude of hypoxic depolarization (HD) didn't exceed 20 mV, was remarkably stable during hypoxic condition (more than 60 min) and returned to the baseline level within 20-30 min after the cessation of CO breathing and releasing of the left carotid artery. Despite the similar durations of the ID and HD, their functional consequences differed greatly. The ID led to a damage of the nervous tissue as evidenced by a reduction of the SD amplitude (to 20-25%) and biphasic change in persistent negative potential (PNP) evoked by the SD wave alone. The 1.5-2-fold increase in the PNP amplitude in the perifocal region was the most prominent outcome of the ID. In contrast to the ID, the SD and PNP characteristics were unchanged after the HD. Such a discrepancy between the ID and HD can be related with their different origin. The results suggest that the HD is produced by blood-brain barrier processes associated with the intensive vasospasm and vasogenic edema. Besides these phenomena, the other well-known factors such as a disturbance of permeability of neuronal membranes, glutamatemediated exitotoxicity, and tissue destruction determine the ID noxious influences.

The role of spreading depression (SD) in the development of ischemic brain damage in rats was studied in two models: focal cortical ischemia provoked by a photothrombotic occlusion of the middle cerebral artery (MCA) and systemic hypoxia induced by breathing with 0.8% carbon monoxide (CO). Spontaneous cortical SD waves occurring during illumination were found to delay the irreversible MCA occlusion. Thrombosis was probably prevented by episodes of striking vasodilation and hyperemia lasting for 1-2 min and accompanying every SD wave. The SD-induced hyperemia after permanent MCA occlusion seems to improve the oxygen supply of the penumbra zone. During hypoxia induced by one-hour respiration with 0.8% CO, COHb saturation of the blood reached 50-60%. SD waves occurred in different brain regions of lightly anesthetized rats (pentobarbital, 20 mg/kg) changed under the above conditions into prolonged depolarizations (HDs) which led to a substantial increase in animals' mortality (60%). The SDs evoked in the cortex and hippocampus of deeply anesthetized rats (pentobarbital, 50 mg/kg) showed that hippocampus became highly vulnerable by CO hypoxia. Duration of the SD-provoked HDs often reached 30-60 min after a single SD wave. Decreased cell density was found in CA1 area of the hippocampus 20-30 days after the CD-enhanced CO hypoxia. Cerebrolysin (2.5 ml/kg daily, during 10 days) prevented from severe hippocampal injury (formation of granulomas) usually seen in the left hemisphere of rats not treated with cerebrolysin.

The persistent negative potential (PNP) developed after a single wave of cortical spreading depression (SD) in the cortex, hippocampus, thalamus, and caudate nucleus. The PNP lasted for about 3-4 hours, its amplitude was 6-7 mV in the ipsilateral and 3-4 mV in the contralateral structures. After development of bilateral primary cortical SD waves the amplitudes of the respective PNP were summed up and reached 9-11 mV. However, after the repeated waves of cortical SD produced with 15-30-min intervals, the PNP level remained unchanged. We think that the PNP is an electrographic manifestation of the well known persistent vasoconstriction after a single wave of cortical SD. It seems to be related with reticular activation due to functional decortication.

Character of spreading depression (SD) wave propagation was studied on two-dimensional model of excitable tissue. It was shown that strips with diminished density of active elements were of different permeability for the waves depending on their front orientation and curvature. When triggered near the border with a rarefied strip the wave could not penetrate through it and the effect of wave "sliding" along this strip was observed. In several-compartment model imitating the diffusely connected cortico-striatal system of the rat brain the sequence of events was determined by a primary focus position. In this model a single stimulus could provoke not only one wave but re-entry waves and reverberators. Described mechanism of repetitive waves generation in inhomogeneous tissue allow to interpret unusual SD wave consequences observed in electrophysiological experiments.

Spreading depression (SD) in the cortex and the caudate nucleus induced by 40 mg/kg i.p. pentylenetetrazole (PTZ) injection was studied in awake rats with implanted carbon electrodes. It was shown that spontaneous bilateral occurrence of cortical SD was the most probable and had an effective inhibitory influence on seizures after the first PTZ application. Penetration of cortical SD waves into the caudate nucleus and their return to the cortex substantially prolonged the anticonvulsive effects of SD. In the course of daily repeated PTZ injections the cortico-caudate SD propagation reduced progressively being accompanied by a decrease of efficiency of its inhibitory effect and interictal spike activity intensification. Similar restriction of SD propagation was observed without any seizure manifestations under the conditions of daily cortical electrical stimulation (without systemic drug treatment). So, reducing the cortico-caudate SD incidence during PTZ kindling is rather the cause of seizure facilitation than its consequence.

Behavioral manifestations of spreading depression (SD) were compared with SD electrophysiological characteristics in these structures. Carbon electrodes were suitable for recording DC slow potential changes in freely moving animal. It was shown that short (0.1 s) high-frequency (200 Hz) electrical stimulation of thalamus and hippocampus with intensity 50-300 microA easily triggered SD wave in these structures in narcotized and awake rats. The threshold of SD occurrence in dorsal hippocampus was the same or sometimes lower than that of the primary afterdischarge. Penetrating SD into ventral hippocampus provoked long latency seizure discharge and wet-dog shakings in awake rats. Intensity of locomotor activity accompanying bilateral hippocampal SD exceeded orienting response significantly. Contrary to hippocampus, thalamic SD was usually subseizure and unilateral phenomenon and had a clear tranquil effect on the rat locomotor activity. It was found that the rats didn't change the compartment preference after 20-45 SD waves in the thalamus or in the hippocampus.

Shifts of steady potentials (SP) in the cerebral cortex of rats were studied during formation of stationary excitation foci by low-frequency electric stimulation and application of penicillin. The dynamics of SP shifts reflects summary effect of depolarization and hyperpolarization processes, actively involved in each cycle of excitation. As a result of functional heterogeneity of different cortical areas, a spontaneously appearing wave of spreading depression (SD) may be transformed into a spiral wave, actively influencing the dynamics of excitation resulting from direct stimulation of the cortex. The cause of long-term inhibition of paroxysmal activity foci may be repeated generation of slow negative waves of SD persisting in conditions of rapid restoration of cortical ability to conduct SD.