Vascular reactivity of the brain in the pigeon Columba livia

In experiments on awake relatively unrestrained pigeons, studies have been made on the reactions of the cerebrovascular bed to fixed functional loads of physical (orthostasis) and chemical (inhalation of hypoxic and hypercapnic gas mixtures) nature. Using hydrogen clearance method, the increase in the intensity of local cerebral blood flow in different structures of the telencephalon during inhalation of the mentioned gas mixtures was demonstrated. Bilateral vagotomy resulted in inversed reactions. Influence of functional loads was accompanied by changes in rheoencephalographic parameters. The data obtained suggest the existence of an evident reactivity of cerebral vessels in birds which is controlled by neurogenic mechanism of regulation of vascular tone.     

Functional state of the frontal cortex and ventromedial hypothalamus during physical overexertion and experimental neurosis in the rabbit

A change of excitability, pO2 and local cortical blood flow under a long-term maximum physical load and in conditions of experimental neurosis, was investigated in rabbits with electrodes implanted in the frontal cortex and ventromedial hypothalamus. It was found that functional activity of these structures under physical orverstrain rises as the blood flow and pO2 increase, and the excitability also increases. In experimental neurosis, a discoordination in functioning of the cortex and hypothalamus is observed. Relative stabilization of the functional state of tested structures, observed during physical overstrain, is absent in conditions of experimental neurosis.     

Blood flow and pO2 in the posterior hypothalamus of cats during paradoxical sleep

In chronic experiments on cats it has been found by recording of the brain local blood flow (BLBF) and of oxygen tension (pO2) in the posterior and anterior hypothalamus, that at sleep phases alternation, the changes of these parameters are differently directed: during the paradoxical sleep the level of BLBF and pO2 oscillations frequency increased in the posterior hypothalamus and decreased in the anterior one. During slow-wave sleep opposite relations were observed. Opposite directions of changes of BLBF level and pO2 oscillations frequency in one and the same phase of sleep show that they are of local origin and must be determined by functional-metabolic shifts. In particular, the increase of BLBF level and frequency of pO2 oscillations must reflect a rise of posterior hypothalamus functional-metabolic activity during paradoxical sleep.     

Effect of fentanyl and morphine on local blood flow and tissue oxygen tension in cortical frontal-parietal area and nucleus accumbens in albino rats

The aim of this study was to examine effects of i.p. injected Fentanyl (0.005 mg/kg) and Morphine (1 mg/kg) on local cerebral blood flow (ICBF) and tissue pO2 level in frontal-parietal area of the cortex and nucleus accumbens of the rat's brain. Either fentanyl or morphine injection resulted in significant increase of local blood flow in the n.accumbens and its decrease in frontal-parietal area of cortex. Measurement of oxygen partial pressure revealed the opposite (to ICBF) changes: a decrease in n.accumbens and its increase in cortical area of the brain. Analysis of this data and electrical activity recorded from both said structures allow to conclude that they are conditioned by respective changes in functional-metabolic activity induced by intraperitoneal injection either fentanyl or morphine: its suppression in frontal-parietal area of the cortex and development of seizure-like activity in the n.accumbens.     

Functional differentiation of the theta-rhythm of the hippocampus in the cat

On the model of discriminating alimentary conditioned reflex with spatial separation of the sources of conditioned (CR, light flashes) and unconditioned (feeding trough) stimuli the theta-rhythm of the dorsal hippocampus was evaluated in cats. Two types of the theta-rhythm were observed in the spectrum of the hippocampal electrical activity: low-amplitude, consisting of a slow growing theta-waves (type I) and high-amplitude consisting of rapidly increasing theta-waves (type II). The type I theta-rhythm is sensitive to noradrenaline and correlates with behavioural forms directed immediately to the realization of alimentary motivation, while the type II is sensitive to serotonin and correlates with behavioural forms directed to the source of the conditioned stimulus. Enhancement of the type II theta-rhythm takes place during a delay of the expected conditioned stimulus. It is suggested that type I theta-rhythm reflects a level of activity of the brain structures connected with unconditioned mechanisms, with realization of biological motivations, while type II theta-rhythm is connected with conditioned reinforcing stimuli; it correlates with various forms of conditioned orienting reflexes and reflects the work of the "nervous model of reinforcing stimulus".     

Continuous measurement of cerebral blood volume in rats with the photoelectric technique: effect of morphine and naloxone

The validity of a photoelectric method for continuous cerebral blood volume (CBV) measurement was tested and modified for the rat's brain. A new way of introducing a miniature light source between the two hemispheres and fixing a light sensitive silicone blue cell to the outer surface of the parietal bone was developed. Light extinction factor of the rat's blood was determined experimentally (Eb rat = 1.38 +/- 0.15) in order to calculate absolute CBV value in this species, resulting in a 4.77 +/- 0.13 vol % absolute CBV value. Data obtained in anesthetized, artificially ventilated rats by simultaneous recording of CBV and local cerebral blood flow (H2-gas clearance technique) show that local hypothalamic blood flow decreased significantly after morphine (1.0 mg/kg s.c.), while total CBV remained unchanged. Opiate receptor blockade with naloxone (1.0 mg/kg s.c.) on the contrary, as well as naloxone and morphine administration, caused no change in local hypothalamic blood flow, but resulted in a significant increase of total cerebral blood volume.     

Factor analysis of the reorganization of the brain structures in patients with multiple sclerosis: A positron emission tomography study

The functional reorganization of the human brain cortex and basal ganglia in patients with multiple sclerosis (MS) was studied. Comparative estimation of the local cerebral metabolic rate of glucose (lCM-Rglu) in regions of interest (ROIs) corresponding to the anatomical and functional brain areas was performed. This research was based on the results of positron emission tomography (PET) of healthy volunteers (n = 31) and patients with the relapsing-remitting and progressive types of MS (n = 59 and 39, respectively). Analysis of the factor structure of the obtained patterns of lCMRglu distribution showed similarity to the factor structure of another functional parameter, the regional cerebral blood flow (rCBF); this indicated that the obtained factor solutions mainly reflected the functional organization of the brain. The differences found in the factor structures of the lCMRglu distribution in patients with different types of MS and healthy volunteers allow us to suggest that, despite the normally close anatomical and functional connections between basal ganglia, these structures are functionally separated in MS patients. The bipolarity of the revealed factors possibly reflects different directions of the processes: deafferentation of particular regions caused a relative decrease in the functional activity in the regions directly responsible for the impaired functions, and a compensatory increase in the functional activity in functionally connected regions.     

Behavioral, electrophysiologic and vegetative correlates of self stimulation in dogs]

Summary electrical activity of different brain structures (chiefly the hippocampal theta-rhythm) and cardiac and respiratory rhythms were recorded during self-stimulation (SS) in dogs. Emotional-motivational excitation in dogs, preceding SS, is attended with a moderate increase in theta-activity in the hippocampus. The SS period is characterized by desynchronization of the electrical activity, the appearance of high-frequency rhythmics and diminished theta-rhythm. After withdrawal of the pedal, hypersynchronization of the theta-rhythm sets in in most of the structures studied. SS is accompanied by considerable shifts of the cardiac and respiratory rhythms. The dynamics of behavioral, electrophysiological and vegetative shifts during SS in dogs points to a successive involvment of the brain mechanisms of search, positive reinforcement and emotional-negative interruption of the pedal pressing series. Complex interaction of the three mechanisms underlies the external phenomenology of the SS instrumental conditioned reflex.     

Distribution of oxygen tension in the brain of spontaneously hypertensive rats

The distribution of cerebral tissue pO2 in spontaneously hypertensive Okamoto-Aoki rats (SHR) and normotensive Wistar-Kyoto rats (WK) was studied by means of polarographic microelectrodes 1-3 microns in diameter. SHR exhibited pO2 shifts towards low values and an increased heterogeneity of pO2 distribution in the cerebral tissue. Morphological studies of the brain have revealed diffuse and focal ischemia in the grey and white matter of the brain in SHR.     

The role of adrenergic structures in the control of cerebral circulation]

A study of the cerebral blood flow carried out by the thermoelectric method demonstrated that stimulation of the cervical sympathetic nerve led to marked changes in the cerebral blood supply. The blood flow changes were two-stage in character: an initial slight increase changed to a decrease below the initial level. Pharmacological analysis with the use of alpha- and beta-adrenoblockers showed a constrictor reaction of the cerebral vessels to be caused by excitation of the alpha-adrenoreactive structures, and the dilatator reaction - by the beta-adrenoreactive structures. An opinion is put forward on a possible mechanism of these changes.     

Seasonal changes in cardiovascular indices and monoamine content in the brain of rabbits

In our previous studies a rather substantial difference between the initial values of the cerebral blood flow was found. On the other hand the brain monoamine content varies in different months of the year when studied. Comparative analysis of these parameters in rabbit brain was the aim of this paper. The content of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in cortical and subcortical structures and the local cerebral blood flow (ICBF), the systemic arterial pressure (SAP) and pulse rate (PR) were studied. There were found seasonal variations in all parameters. A certain LCBF retardation in subcortical structures and cortex and the weakest effect of the stimulation was observed in May. There was a drop in SAP and some PR increase in the spring (April-May). Brain NA and 5-HT content showed seasonal changes with the lowest values near the winter months and reaching maximum in May as the PR does. Content of DA was low in May. So it seams possible that the ion ICBF in May can be explained by the decrease of brain DA at that time. The ICBF and the reactivity of cerebral microvessels seem to depend on the monoamine content and show seasonal variability.     

Local and global cerebral blood flow and glucose utilization in the α-galactosidase A knockout mouse model of Fabry disease

Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency.     

Infrared method of studying the action of vasoactive substances on cerebral circulation

A method for the investigation of cerebral blood flow changes under the influence of vasoactive drugs has been suggested. The method is based on continuous infrared radiation and registration of the reflection from the local brain region through the cerebral cranium. The experiments were conducted on anesthetized cats. The dependence of Pa CO2 on the recorded parameters is shown. The changes in the cerebral blood flow (in conventional units) determined by the alterations of the infrared radiation reflection are shown upon the injection of 1.2 microgram/kg, 2.5 micrograms/kg and 5 micrograms/kg of noradrenaline.     

The functional state classification and evaluation of the stability level in mental loads based on the factor structure of heart rate variability parameters

In the paper, outcomes of the researches devoted to factor analysis of heart rate variability parameters and definition of the most informative parameters for diagnostics of functional states and an evaluation of level of stability to mental loads, are presented. The factor structure of parameters, which unclude integral level of heart rate variability (1), balance between activity of vagus and brain cortical-limbic systems (2), integrated level of cardiovascular system functioning (3), is substantiated. Factor analysis outcomes have been used for construction of functional state classification, for their differential diagnostics, and for development and check of algorithm for evaluation of the stability level in mental loads.     

Cerebral Blood Oxygenation Measurement Based on Oxygen-dependent Quenching of Phosphorescence

Monitoring of the spatiotemporal characteristics of cerebral blood and tissue oxygenation is crucial for better understanding of the neuro-metabolic-vascular relationship. Development of new pO2 measurement modalities with simultaneous monitoring of pO2 in larger fields of view with higher spatial and/or temporal resolution will enable greater insight into the functioning of the normal brain and will also have significant impact on diagnosis and treatment of neurovascular diseases such as stroke, Alzheimer''s disease, and head injury.Optical imaging modalities have shown a great potential to provide high spatiotemporal resolution and quantitative imaging of pO2 based on hemoglobin absorption in visible and near infrared range of optical spectrum. However, multispectral measurement of cerebral blood oxygenation relies on photon migration through the highly scattering brain tissue. Estimation and modeling of tissue optical parameters, which may undergo dynamic changes during the experiment, is typically required for accurate estimation of blood oxygenation. On the other hand, estimation of the partial pressure of oxygen (pO2) based on oxygen-dependent quenching of phosphorescence should not be significantly affected by the changes in the optical parameters of the tissue and provides an absolute measure of pO2. Experimental systems that utilize oxygen-sensitive dyes have been demonstrated in in vivo studies of the perfused tissue as well as for monitoring the oxygen content in tissue cultures, showing that phosphorescence quenching is a potent technology capable of accurate oxygen imaging in the physiological pO2 range. Here we demonstrate with two different imaging modalities how to perform measurement of pO2 in cortical vasculature based on phosphorescence lifetime imaging. In first demonstration we present wide field of view imaging of pO2 at the cortical surface of a rat. This imaging modality has relatively simple experimental setup based on a CCD camera and a pulsed green laser. An example of monitoring the cortical spreading depression based on phosphorescence lifetime of Oxyphor R3 dye was presented. In second demonstration we present a high resolution two-photon pO2 imaging in cortical micro vasculature of a mouse. The experimental setup includes a custom built 2-photon microscope with femtosecond laser, electro-optic modulator, and photon-counting photo multiplier tube. We present an example of imaging the pO2 heterogeneity in the cortical microvasculature including capillaries, using a novel PtP-C343 dye with enhanced 2-photon excitation cross section.Click here to view the related article Synthesis and Calibration of Phosphorescent Nanoprobes for Oxygen Imaging in Biological Systems.Download video file.^{(53M, mov)}     

Analysis of the theta-rhythm of the rabbit neocortex by estimation of particular coherence functions

Situations characterized by differences in the genesis of the theta-rhythm were distinguished by the analysis of activity recorded simultaneously from various points of the rabbit neocortex and hippocampus by means of the estimation of particular coherence functions. With maximal cross-correlation between potentials from different parts of the neocortex, in most cases (not less than 75%) the high coherence of these potentials in the theta-band is determined by a theta-rhythm generated actually in the neocortex. In about 20% of cases the high coherence of these potentials may be the result of the passive conduction of hippocampal theta-activity to the surface of the neocortex. To increase the likelihood of the passage of excitation from the afferent to the effector system active generation of rhythmic waves in the theta-band in both the neocortex and hippocampus is essential. Rhythmic processes in both structures must be coherent with each other.     

Changes in the frequency of the hippocampal theta-rhythm in the dog exposed to a conditioned food stimulus

Frequency changes of hippocampal theta-rhythm in the process of elaboration of coinciding or delayed instrumental alimentary reflex was studied in two dogs. Determination of dominating frequency of rhythmical activity was carried out by means of mathematical methods of analysis on a computer. It was found out, that during the action of conditioned alimentary stimulus the frequency of dominating oscillations became enhanced. Animals with a more frequent initial theta-rhythm formed the delayed alimentary reflex more rapidly.     

Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism

The purpose of the present investigation was to examine the effects of an extract of Ginkgo biloba (EGB) on blood glucose levels, on local cerebral blood flow as well as on cerebral glucose concentration and consumption. The local cerebral blood flow (LCBF) was measured in conscious rats by means of the 14C-iodoantipyrine technique and local cerebral glucose utilization (LCGU) by 14C-2-deoxy-glucose autoradiography. EGB increased the LCBF in 39 analyzed, anatomically defined brain structures by 50 to 100 per cent. No influence of EGB on LCGU was demonstrable. However, EGB enhanced the blood glucose level dose-dependently. Substrates and metabolites of energy metabolism were measured in the cortex of the isolated rat brain perfused at constant rate and with 7 mmol/l glucose added to the perfusion medium. In these experiments EGB decreased the cortical glucose concentration without other substrate levels being changed. These results suggest that glucose uptake may be inhibited by EGB. It is argued that the effects of EGB on brain glucose concentration and blood flow may contribute to its protection of brain tissue against ischemic or hypoxic damage.     

Microwave method of determining cerebral blood flow

A noninvasive method of quantitative assessment of cerebral blood flow based on heat clearance from brain tissues is described. The rate of heat clearance depends essentially on the blood flow. The employment of microwave techniques permits to warm the investigated brain zone and to record the temperature decrease extracranially. As a thermometer, a microwave radiometer was used. The experiments were carried out on cats. The method was tested by current vasoactive drugs.