Protective effect of cerebrocrast on rat brain ischaemia induced by occlusion of both common carotid arteries

Diabetes mellitus is accompanied by several cardiovascular complications including atherosclerosis, cerebral ischaemia and stroke. We examined the neuroprotective effect of a 1,4-dihydropyridine derivative cerebrocrast (C, a new antidiabetic agent, synthesized in the Latvian Institute of Organic Synthesis) on the level of ATP in the brain, and on changes of the EEG and ECG, as well as blood pressure parameters in anaesthetized Wistar male rats before and during 10-min occlusion of both common carotid arteries. Cerebrocrast was administered i.v. at doses of 1.0 and 10 microg/kg in the v. femoralis 20 min prior to ischaemia. After 10-min ischaemia animals were decapitated and the brain was immediately frozen in liquid nitrogen and subsequently used for analysis of changes of ATP contention. Cerebrocrast, administered at doses of 1.0 and 10 microg/kg 20 min prior to occlusion of both common carotid arteries, completely prevented a fall in the ATP content of brain compared with the control rats. In control rats the content of ATP in brain during ischaemia decreased from 2.77 +/- 0.22 (basal level) to 1.74 +/- 0.20 micromol/g as a result of ischaemia. By administration of cerebrocrast 20 min before occlusion of the arteries, the content of ATP in the brain remained at the level of preischaemia (1.0 microg/kg C + ischaemia 2.82 +/- 0.36; 10 microg/kg C + ischaemia 2.42 +/- 0.22 micromol/g). Analysis of EEG parameters both before and during 10 min of occlusion showed that at a C dose of 1.0 microg/kg before occlusion produced a regular alpha rhythm during ischaemia and prevented cerebral bioelectric activity from significant changes. The depression of basal rhythm was observed at a C dose of 10 microg/kg during ischaemia in two rats out of six as well as an increase in the ECG ST segment above the isoelectric line. Blood pressure was decreased by about 10-20 mm Hg. We propose that pretreatment of rats with cerebrocrast at doses of 1.0 or 10 microg/kg 20 min prior to ischaemia can prevent ischaemic damage of rat brain, maintain necessary energy consumption, promote ATP production in brain cells, and prevent significant changes in EEG and ECG parameters. These properties are important in diabetes mellitus and its evoked cardiovascular complications as stroke, ischaemia, etc.     

Effects of weak solutions of aldehydes on EEG changes in rats

Alternations of EEG have been investigated after single intraarterial infusion of formaldehyde, glutaric aldehyde and its mixture in 50 adult male rats. The dissolved solutions of aldehydes were shown to have complicated inhibitive activity which consists of two phases. The first phase of EEG inhibition rapidly develops and it isn't very long in its duration. The second one is much more durable. Formaldehyde causes the first phase of inhibition in general, though glutaric aldehyde promotes especially the appearance of the second phase. The mixture of two aldehydes demonstrates synergic activity which is shown as significant increase of EEG inhibition as compared to individual inhibitive activity of aldehydes. The inhibitive influence of aldehydes is fully reversible, nonspecific and doesn't cause post-experimental disorders. The highest effect of brain protection from ischaemia damages coincides with development of maximum inhibition of specific brain functions during the second phase of EEG depression.     

Time-dependent changes in superoxide dismutase, catalase, xanthine dehydrogenase and oxidase activities in focal cerebral ischaemia

Time-dependent changes in the activities of antioxidant enzymes and an oxidant enzyme, xanthine oxidase (XO), were detected in primary and peri-ischaemic brain regions during permanent occlusion of the middle cerebral artery (MCAO) in rats. There were no changes in superoxide dismutase (SOD) and catalase (CAT) activities after 3 h of MCAO, whereas antioxidant enzyme activities decreased significantly in ischaemic brain areas following 24 h of ischaemia. After 48 h, the enzyme activities returned to the baseline but then a further increase was observed in ischaemic brain areas by 72 h post-ischaemia. Normally, XO exists as a dehydrogenase (XD), but it is converted to XO which contributes to injury in some ischaemic tissues. The XO activity increased slightly at 3 h after ischaemia, but after 24 h of ischaemia it returned to the baseline and then remained relatively unchanged in ischaemic areas. Pretreatment with allopurinol before ischaemia prevented changes in SOD and CAT activities and attenuated brain oedema during 24 h of ischaemia. Neither XO nor XD activity changed in allopurinol-treated rats at the times of ischaemia. These results indicated that ischaemic brain tissue remained vulnerable to free radical damage for as long as 48 h after ischaemia, and XO was probably not an important source of free radicals in cerebral ischaemia.     

Influence of protective drugs on the EEG during short-term transient ischaemia

Influence of drugs on the cessation time of the brain electrical activity (resistance time) during total cerebral ischaemia evoked by clamping of the aorta for 50 sec; on the duration of its reappearance during reperfusion (restitution time) and on the background activity of EEG were studied. The experiments were carried out in 7 groups. Each group contained 5 animals. Nine clampings with intermittent reperfusion periods of 10 min were performed in each animal. One group served as control. In the remaining ones after the first three clampings the animals were given Glyo-6, Nootropil, Verpamil, Epanutin, Inactin or Lidocain. The resistance and restitution times measured in the control group as well as the reproductibility of the power spectrum values of the EEG provided evidence for the stability of the model. Glyo-6 in a dose of 10 mg/kg, Nootropil in a dose of 100 mg/kg or Verpamil in a dose of 0.125 mg/kg did not alter the above-mentioned parameters. As an effect of the administration of Epanutin in a dose of 10 mg/kg, the resistance time increased slightly, whereas restitution time decreased significantly. Administration of Inactin in a dose of 15 mg/kg, or Lidocain in a dose of 100 mg/kg increased considerably resistance time for a period of about one hour. The results indicate that in the initial phase of ischaemic brain damage both the cessation of EEG activity and the restitution during reperfusion after short-term occlusion of the circulation can be influenced favourable with drugs which decrease cerebral metabolism, inhibit synaptic transmission and have membrane stabilizing effect.     

EEG characteristics of bioelectrical activity of the brain in women with normal and complicated pregnancy

Spectrum and coherent EEG analysis has been made at 109 pregnant women during 35-36 weeks of gestation. It has been shown, that functional interhemispherical asymmetry of the brain is the sensible parameter of normal and complicated gestation. It has been found out that as for normal pregnancy prevailing activation in central and temple areas of the brain contralateral to the side of placenta placement in uterus is characteristic. The development of gestation complications accompanied by the inversion of interhemispherical asymmetry of EEG activation. It was pointed out that correlative relations of bioelectrical activity of the brain in women with normal gestation are the indicator of dominating of nervous centers of left hemisphere in the integrational process.     

The hippocampus as the determinant structure generating epileptic activity during korazol kindling

It has been shown in chronic experiments on rats that two periods of EEG and behavioral alterations may be distinguished during korazol kindling. The bursts of slow waves and spike-wave activity appear on the EEG during the first period as response to subthreshold doses of korazol, which is accompanied behaviorally by standing and myoclonuses. The second period is characterized by the appearance of high-frequency polymorphous generalized seizure discharges on the EEG accompanied by clonicotonic seizures. Interictal and ictal epileptic discharges appear primarily in the hippocamp and then in other brain structures during the development of korazol kindling. The conclusion is made that the hippocamp plays the role of a pathological determinant structure in the development of chronic brain epileptization during korazol kindling.     

Long-range temporal correlations in the EEG bursts of human preterm babies

The electrical activity in the very early human preterm brain, as recorded by scalp EEG, is mostly discontinuous and has bursts of high-frequency oscillatory activity nested within slow-wave depolarisations of high amplitude. The temporal organisation of the occurrence of these EEG bursts has not been previously investigated. We analysed the distribution of the EEG bursts in 11 very preterm (23-30 weeks gestational age) human babies through two estimates of the Hurst exponent. We found long-range temporal correlations (LRTCs) in the occurrence of these EEG bursts demonstrating that even in the very immature human brain, when the cerebral cortical structure is far from fully developed, there is non-trivial temporal structuring of electrical activity.     

Functional interrelation of the brain structures of the cat during the generation of rhythmic activity. I. The frequency characteristics of the electroencephalogram

The similarity of frequency parameters of electroencephalograms (EEG) recorded from visual, associative and sensorimotor cortical area, caudate nucleus and several thalamic nuclei have been analysed using the period analysis of EEG and cluster analysis of data obtained to clarify the functional interrelationships between these parts of the brain during generation of rhythmic activity of different types. Functional interrelationships between brain structures in freely moving cats during the states of drowsiness and slow-wave sleep have been shown to differ from "classical" thalamo-cortical pacemaker relations.     

THE RELEASE OF BRAIN FREE FATTY ACIDS DURING ISCHAEMIA IN ESSENTIAL FATTY ACID-DEFICIENT RATS

—The release of free fatty acids and especially of free arachidonic acid occurring in rat brain during ischaemia has been studied in essential fatty acid-deficient animals. Free fatty acid levels are lower in essential fatty acid-deficient brains before and especially after 5 min of ischaemia. The percentage of arachidonic acid, in respect of total free fatty acids, is similar in both control and essential fatty acid-deficient brains before ischaemia (0 min), but is greatly reduced in deficient brains in respect of controls after ischaemia (5 min). Total levels of free arachidonic acid are thus greatly reduced after ischaemia in the brain of essential fatty acid-deficient rats. Focussed microwave irradiation of the brain, a technique which instantaneously kills the animals, and which was used for the determination of brain basal levels of free fatty acids and free arachidonic acid, does not per se modify brain lipid and fatty acid composition.     

Photoperiodism and changes in brain bioelectric activity in schoolchildren in the arctic zone

The dynamics of the main electroencephalographic patterns and their relationship with natural illumination periods have been described in this study. We have determined periods, which are the most favorable for brain functioning and development of cognitive function in northerner schoolchildren. We have found that adaptive changes in bioelectric activity of the brain take place during transitional seasons. An increase in the activity of all EEG rhythms in spring and predominance of the slow-wave Δ and θ activity in autumn have been found. The discovered dynamics of amplitude and spectral parameters of EEG are not dependent on age-related changes. The formation of bioelectric activity of the brain in northerner schoolchildren was mostly affected by the sex of a child and changes in the daytime duration.     

Anti-ischemic protection of the brain using water-soluble form of aspirin-acelisin]

The domestic water-soluble aspirin (acelisin) has been used as an anti-ischemic brain protector. The total brain ischemia has been implemented in accordance with an original technique for 17 to 35 min. The doses of acelisin from 25 to 250 mg/kg have been tested during experiments. The infusion of solutions has been carried out before ischemia, 15 min before reperfusion and just after the beginning of reperfusion. The functional status and survival of rats have been evaluated during a week. The best result has been reached with 150 mg/kg acelisin injected 30 min before ischaemia. A positive effect was reported when acelisin was used in early postischaemic period.     

EEG Mu Rhythm in Typical and Atypical Development

Electroencephalography (EEG) is an effective, efficient, and noninvasive method of assessing and recording brain activity. Given the excellent temporal resolution, EEG can be used to examine the neural response related to specific behaviors, states, or external stimuli. An example of this utility is the assessment of the mirror neuron system (MNS) in humans through the examination of the EEG mu rhythm. The EEG mu rhythm, oscillatory activity in the 8-12 Hz frequency range recorded from centrally located electrodes, is suppressed when an individual executes, or simply observes, goal directed actions. As such, it has been proposed to reflect activity of the MNS. It has been theorized that dysfunction in the mirror neuron system (MNS) plays a contributing role in the social deficits of autism spectrum disorder (ASD). The MNS can then be noninvasively examined in clinical populations by using EEG mu rhythm attenuation as an index for its activity. The described protocol provides an avenue to examine social cognitive functions theoretically linked to the MNS in individuals with typical and atypical development, such as ASD.      

EEG correlation and impulse activity of neuronal populations of individual structures of the cat brain during elaboration and reproduction of motor and alimentary reactions in instrumental conditioned reflexes]

Stable changes in EEG and spike activity of neuronal populations in different brain formations were studied on models of instrumental conditioned reflexes: motor and motor alimentary. A depencence has been established of the EEG amplitude-frequency parameters in the motor and striate cortical zones and the hippocampus on definite changes of unit spike activity in these areas. Simultaneous recording of the EEG and the spike activity of neuronal populations helps to elucidate the neurophysiological nature of individual rhythms of bio-electrical activity. Learned animals exhibit a stable reproduction of the spatial-temporal EEG patterns and motor alimentary reactions when automatic presentation of reinforcement is changed over to an arbitrary one.     

Analysis of the brain bioelectrical activity of the suslik Citellus parryi during hibernation

Computer analysis has been made of the diurnal rhythm of the brain activity in the ground squirrel Citellus parryi during hibernation (body temperature 7-8 degrees C). The data obtained are presented in the form of graphical plots with two-dimensional density of probability of distribution of intermittent bursts of spindles and isoelectric EEG.     

The reflection of compensation processes in the structure of the EEG spatial-temporal relationships in patients with disordered brain regulatory mechanisms]

Studies of intercentral relations of electrical activity in the cerebral cortex of the patients with hypophysis tumours under the conditions of chronic (before operation) and acute (after tumour ablation, early post-operative period) influence of the focus on the regulatory brain systems allowed to reveal definite changes of spectral-coherent EEG characteristics, reflecting the functional state of the cerebral adaptive-compensatory apparatus. It has been shown that reciprocal character of changes of various forms of the brain electrical activity and their intercentral relations is one of manifestations of development of the processes of cerebral compensation. At the same time, global fall of the EEG intercentral relations indicating the disintegration of the cerebral functional connections, reflects a loss of CNS compensatory mechanisms. The revealed EEG-characteristics at the present time are applied in Burdenko Institute of Neurosurgery for diagnostic-prognostic estimation of the brain functional state in patients during pre- and post-operative period.     

Post-radiation effect on the interhemispheric asymmetry in EEG and thermography characteristics

Complex analysis of EEG and thermographic parameters carried out in 10 healthy subjects and 34 patients, Chernobyl clean-up participants revealed a correlation between EEG and brain temperature changes in the baseline state and during mental arithmetic. During cognitive activity the maximal increase in the average EEG coherence and temperature shifts in healthy subjects were observed in the left frontotemporal and right parietotemporal areas. In patients changes in both parameters under study were most pronounced, the interhemispheric relations were impaired. The visual analysis revealed "flat" and "hypersynchronous" EEG types in patients. The dominant pathologic activity in the betal range indicative of mediobasal and oral brainstem lesions was characteristic of the flat EEG. This type of activity was observed in 60% of patients. In these cases, a general decrease in EEG coherence and temperature was most pronounced in the left hemisphere. The hypersynchronou EEG type (40% patients) was characterized by paroxysmal activity in the theta and alpha ranges suggesting diencephalic brain lesions. In these cases, EEG coherence and temperature were more variable; changes in the right hemisphere were significant, be it increase or decrease. Our complex approach to investigation of brain activity in different aspects seems to be promising in estimation of the brain functional state both in healthy persons and patients in remote terms after exposure to radiation. The specific hemispheric temperature changes revealed in Chernobyl patients especially during cognitive activity can be the sequels of postradiation disorders of vascular neuro-circulation. The EEG findings suggest subcortical disorders at different levels (diencephalic or brainstem) and functional failure of the right or left hemispheres in remote terms after exposure to radiation.     

Brain Metabolism and Intracellular pH During Ischaemia: Effects of Systemic Glucose and Bicarbonate Administration Studied by 31P and 1H Nuclear Magnetic Resonance Spectroscopy In Vivo in the Lamb

Brain metabolism and intracellular pH were studied during and after episodes of incomplete cerebral ischaemia in lambs under sodium pentobarbitone anaesthesia. 31P and 1H magnetic resonance spectroscopy was used to monitor brain pHi and brain concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), beta-nucleoside triphosphate (beta NTP), and lactate. Simultaneous measurements were made of arterio-cerebral venous concentration differences (AVDs) for oxygen, glucose, and lactate. Cerebral ischaemia was induced by a combination of bilateral carotid clamping and hypotension, and the acute effects of systemic administration of glucose and sodium bicarbonate were examined. The molar ratio of glucose to oxygen uptake by the brain (6G/O2) increased above unity during cerebral ischaemia. Statistically significant AVDs for lactate were not observed. Cerebral ischaemia was associated with a reduction in brain pHi PCr/Pi ratio, and an increase in brain lactate. No effect of arterial plasma glucose on brain lactate concentration or brain pHi was evident during cerebral ischaemia or in the postischaemic period. Administration of sodium bicarbonate systemically in the postischaemic period was associated with a rise in arterial and brain tissue PCO2. A fall in brain pHi occurred which was attributable in part to coincidental brain lactate accumulation. The increase in brain lactate measured by 1H nuclear magnetic resonance in vivo during ischaemia was insufficient to account for the change in buffer base calculated to have occurred from previous estimates of brain buffering capacity.     

Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia

Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (≥3 g/m² die), 4 with standard dose (100 mg/m² die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6 months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.     

Alpha-Theta Effects Associated with Ageing during the Stroop Test

The Stroop effect is considered as a standard attentional measure to study conflict resolution in humans. The response of the brain to conflict is supposed to change over time and it is impaired in certain pathological conditions. Neuropsychological Stroop test measures have been complemented with electroencephalography (EEG) techniques to evaluate the mechanisms in the brain that underlie conflict resolution from the age of 20 to 70. To study the changes in EEG activity during life, we recruited a large sample of healthy subjects of different ages that included 90 healthy individuals, divided by age into decade intervals, which performed the Stroop test while recording a 14 channel EEG. The results highlighted an interaction between age and stimulus that was focused on the prefrontal (Alpha and Theta band) and Occipital (Alpha band) areas. We concluded that behavioural Stroop interference is directly influenced by opposing Alpha and Theta activity and evolves across the decades of life.     

THE EFFECT OF LIMB ISCHAEMIA ON THE TURNOVER OF NORADRENALINE IN THE HYPOTHALAMUS AND BRAIN STEM OF THE RAT

The effect of ischaemic limb injury on the turnover of noradrenaline in the hypothalamus and brain stem has been studied in rats. There are theoretical reasons for thinking that these regions are activated in trauma and previous work showed that during limb-ischaemia the concentration of noradrenaline in the hypothalamus decreased by 27 per cent. The tourniquets were applied to both hind-limbs 1 h after the injection of [¹⁴C]-tyrosine when the labelling of the noradrenaline was maximal. During 4 h limb ischaemia the endogenous tyrosine concentration in the plasma decreased while that in the hypothalamus first rose and then fell. Changes in a similar direction in the brain stem were not statistically significant. Limb ischaemia did not affect the decline in the specific activity of the plasma or tissue tyrosine. It was concluded that the injury increased the utilization of tyrosine by the body. During the 4 h bilateral hind-limb ischaemia the rate of decline of [¹⁴C]noradrenaline was significantly increased in the brain stem but not in the hypothalamus. Conditions in the brain stem were sufficiently close to ‘steady-state’ to be able to conclude that the injury increased the metabolism of noradrenaline in the brain stem. Conditions in the hypothalamus were too complicated for definite conclusions to be drawn. The possible reasons for this and the limitations of this method for studying noradrenaline turnover are discussed.