Evolution of the regional blood deficit and energy metabolism after induction of transient cerebral ischemia by occlusion of the vertebral and carotid arteries in the rat

A transient brain ischemia of 10 min duration was produced in rats by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. Ischemia reduced blood flow to 10-18% of the control values in forebrain structures (cortex, striatum, thalamus) and to 25-50% in the mesencephalon, cerebellum and brain stem. In these last structures, after 30 min of recirculation, the flow rates returned to normal values but a 20-35% reduction of blood flow was present in the forebrain structures, indicating that the development of the postischemic hypoperfusion was related to the severity of the preceding ischemia. After 30 min of recirculation, there was a near complete recovery of the high energy compounds but a residual metabolic dysfunction was evidenced by an increase in lactate/pyruvate ratio and an elevation of the glucose content, suggesting a depression of cerebral metabolism which may account for the brain hypoperfusion.     

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.     

Regional cerebral blood flow changes during hypothermia

1. 1. When brain temperature was decreased from 38 to 22 °C using selective hypothermia, tissue blood flow decreased significantly in cerebral cortex, cerebellum, and thalamus, but did not significantly change in hypothalamic or brain stem tissue.

2. 2. A further decrease in brain temperature to 8 °C produced an increase in blood flow in all tissues except cerebral cortex compared to tissue blood flow measured at 22 °C. Compared to normothermic values, blood flow remained significantly decreased at 8 °C in cerebral and cerebellar cortex and was increased in brain stem.

3. 3. After rewarming, tissue blood flow returned to original baseline values in all tissues except cerebral cortex where blood flow was slightly but significantly decreased and brain stem, where blood flow was increased.

4. 4. These results indicate that the cerebrovascular effects of selective brain cooling are regionally specific. These changes appear to be due to both direct and indirect effects of cerebral hypothermia since brain tissue blood flow changes are apparent, compared to control values, after rewarming of the brain.

     

Cerebrovascular reserve in the cat after acute bilateral carotid occlusion

Cerebral blood flow in the cat was studied before and after acute bilateral common carotid occlusion under normocapnic and hypercapnic conditions and after induced hypotension. Regional blood flow to different brain structures was studied with the microsphere method. Local blood flow in the caudate nucleus, the cerebral cortex and medulla oblongata was studied with H2-polarography. Although the blood flow to the anterior brain regions is significantly decreased after bilateral common carotid occlusion, their blood supply is kept above ischaemic levels by re-distribution of the vertebrobasilar flow. Cerebrovascular reserve in anterior brain regions, however, is lost as indicated by the severe impairment of both the flow response to hypercapnia and to blood pressure decrease. After bilateral common carotid occlusion paradoxical CO2-reactions, indicating intracerebral steal, were seen in the caudate nucleus. In posterior brain regions resting blood flow, flow-reaction to hypercapnia and to hypotension are better preserved under these conditions. Measurement of the CBF responses to induced hypercapnia is a dependable test for appreciation of cerebrovascular reserve after cerebrovascular occlusion but may be potentially hazardous where local flow is close to ischaemic levels.     

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.     

Functional organization of the cortico-reticular system of the brain in response to physical loads

An estimation was carried out by factor analysis method of informative value of alpha-like rhythm, EEG theta-rhythm, local cerebral blood filling and oxygen tension (pO2) in estimation of functional state of cerebral structures under submaximal physical loads. Experiments were carried out on 35 rabbits with electrodes chronically implanted in the sensorimotor cortex and reticular formation. The obtained values were processed by a variant of factor analysis--a method of main components. For interpretation of factor loads matrix an orthogonal turn of factor axes was carried out according to varimax criterion. It has been established that informative value of the parameters depends on the brain structure where the given parameters were defined. Dynamics of pO2 and the theta-rhythm mostly influence the changes in other parameters. The states of structures before and during the period of physical load after-effect are mostly characterized by the brain local blood filling and less by the theta-rhythm amplitude.     

Kinetic properties of the 5 alpha-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain

The 5 alpha-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5 alpha-reductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5 alpha-reductase has a higher activity in immature animals. This study was performed in order to verify whether the differences in the 5 alpha-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60-90-day-old), immature (23-day-old), and aged (greater than 20-month-old) male rats. The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 +/- 0.2, 2.72 +/- 0.73 and 3.83 +/- 0.49 microM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 +/- 5.54), in the white matter (19.57 +/- 2.36) and in the cerebral cortex (6.47 +/- 1.03 ng/h/mg protein) of adult animals have been found to be consistently different. Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 +/- 0.11 and 3.39 +/- 0.75 microM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 +/- 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 +/- 5.54); a Vmax (34.31 +/- 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats.     

Analysis for Distinctive Activation Patterns of Pain and Itchy in the Human Brain Cortex Measured Using Near Infrared Spectroscopy (NIRS)

Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (τ = +18.7 sec) and itch (τ = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.     

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.     

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.     

Total RNA content and blood flow in rat brain after RNA administration

The changes in blood flow through selected brain structures and the changes in the total RNA content of cells of these structures were examined after a single administration of yeast RNA to 6-month-old male rats. The total content of ribosomal RNA in cells of the limbic system (septum, hippocampus, hypothalamus) increased 48 hrs after the administration of 100 mg i.p. yeast RNA , dropped after 7 days (in hypothalamus), 21 and 30 days (in hippocampus), 30 days (in septum). In cells of the limbic system as a whole there is a higher total RNA content in experimental rats. No changes were observed in the cells of parietal brain cortex. Blood flow increased in limbic structures 21 and 30 days after RNA administration and in septum and in hippocampus also 90 days after application. No changes were observed in parietal brain cortex, bulbi olfactorii, cerebellum and brain stem. Histochemical changes correlated positively with blood flow changes in the limbic system 14, 21, 30 and 90 days after RNA application. The body weight of experimental rats did not differ from that of control animals. The changes in haemodynamic parameters were transient and were demonstrated as fluctuations in heart rate, cardiac output, and peripheral resistance. Blood pressure experienced no changes.     

Comparative Effect of Transient Global Ischemia on Extracellular Levels of Glutamate, Glycine, and γ-Aminobutyric Acid in Vulnerable and Nonvulnerable Brain Regions in the Rat

We evaluated whether regional differences in the magnitude of glutamate, gamma-aminobutyric acid (GABA), and glycine release could explain why some regions are vulnerable to ischemia whereas others are spared. By means of the microdialysis technique, the temporal profile of ischemia-induced changes in extracellular levels of glutamate, GABA, and glycine was compared in regions that demonstrate differing susceptibilities to a 10- and 20-min ischemic insult (dorsal hippocampus, anterior thalamus, somatosensory cortex, and dorsolateral striatum). The degree of ischemia (as established by local cerebral blood flow reduction) and the magnitude of histopathological neuronal damage were also evaluated in these regions. The blood flow reduction was severe and uniform in all regions; however, the histopathological outcome illustrated a different pattern. Whereas the CA1 sector of the hippocampus was severely damaged, the thalamus and cortex were relatively spared from both 10 and 20 min of ischemia. Striatal neurons were resistant to a 10-min insult but severely damaged after 20 min of ischemia. Ischemia-induced increase in glutamate and GABA content were of a similar magnitude and temporal profile in all four brain regions. A uniform increase in extracellular glycine levels was also observed in all four brain structures. The postischemic response, however, was different. Glycine levels remained twofold higher than baseline in the hippocampus but fell to baseline in the cortex and thalamus after both 10- and 20-min insults. In the striatum, glycine levels returned to baseline after 10 min of ischemia but remained relatively high after a 20-min insult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI

Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data. These results open the door to a new type of fMRI analysis that more accurately reflects the true neuronal activity.     

Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.     

Binding of Paroxetine to the Serotonin Transporter in Membranes from Different Cells,Subcellular Fractions and Species

The binding of [³H]-paroxetine to membrane serotonin transporter (SERT) has been studied in membranes from different sources and subcellular fractions. From rat were membranes from venous blood platelets, brain total cortex, brain microsomes, brain crude and purified synaptosomes. Membranes were obtained from venous blood platelets from human volunteers and from brain cortex tissue from neurosurgery (cerebral lobectomies following craniocerebral injuries). The main finding was that the K _D of paroxetine binding to the SERT was the same for platelet and nerve ending (synaptosomal) membranes. That parameter was significantly lower in membranes from brain microsomes and cortex total tissue. No species related difference was found, where comparison was possible, between human and rat tissue. The equality of K _D of paroxetine binding to blood platelet membranes and to membranes from nerve endings appears to encourage the use of such membranes as a model for brain SERT. Binding at two different temperatures for several of the fractions suggests that paroxetine–SERT interaction is entropy-driven.     

Local blood flow in the dorsal hippocampus and cerebellar cortex in progeny of iodine-deficient rats

Experimental studies show depressive behavior in rats caused by hypothyroidism and antidepressant effect of thyroid hormones. The present study analyses changes in the hippocampal and cerebellar cortex local blood flow in the progeny of rats suffering from iodine deficiency before mating and during the whole period of gestation. The diet with very low iodine content results in a decrease of local blood flow in both brain structures, but the greatest changes were observed in hippocampus. Addition of the iodine to the diet eliminates the above blood flow changes.     

Conceptual approaches to revealing the function of the structural organization of a neuronal network

Brain is an unexcelled instrument of perception and analysis of intensive information flows and decision making. Joint achievements of neurophysiology and morphology highlight the pathways between neuronal formations of different brain regions and their functions and fine organization of relationships within these formations. However, the principles of information transmission and signal processing in such structures remain hypothetical. The structure of the network executing the function of extrapolation or prediction of input signal values is discussed. Organization of neurons in this network is compared with relationships of neurons in the cerebellar cortex. It is suggested that the considered organization of neuronal relationships and the functions executed by the network are inherent for all brain formations including the brain cortex.     

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.     

Regional distribution of cerebral blood flow during exercise in dogs

This study was performed to determine whether exercise produces vasodilatation in regions of the brain that are associated with motor functions despite the associated vasoconstrictor effect of hypocapnia. Total and regional cerebral blood flow (CBF) were measured with microspheres in dogs during treadmill exercise of moderate intensity. Flow was also measured at rest after stimulation of ventilation with doxapram. During moderate exercise, total CBF was not changed significantly, but regional flow was increased in structures associated with motor-sensory control; blood flow to motor-sensory cortex, neocerebellar and paleocerebellar cortex, and spinal cord increased 30 +/- 7%, 39 +/- 8%, and 29 +/- 4%, respectively (P less than 0.05). After doxapram, which increased arterial blood pressure and decreased arterial PCO2 to levels similar to those during exercise, total CBF decreased and there was no redistribution of CBF. These results indicate that exercise in conscious dogs increases blood flow in regions of the brain associated with movement despite the associated vasoconstrictor stimulus of arterial hypocapnia. Thus, during exercise, local dilator influences that presumably result from increases in metabolism predominate over a potent constrictor stimulus in regulation of cerebral vascular resistance.     

Functional interrelations of brain structures in the cat during the generation of rhythmic activity. III. Cluster analysis of rhythmic indices

The functional interrelationships of the brain structures of freely moving cats in generation of rhythmic EEG activity during the states of drowsiness and light sleep were evaluated using the claster analysis of mean values indexes of rhythms in different structures as well as correlation coefficients between them in time. It was shown that according these parameters visual cortical areas and lateral geniculate body appeared in different clusters. Lateral geniculate body suggested not to be the only pacemaker of EEG rhythms in visual cortex. The wide convergence of subcortical inputs to the visual cortex and possibility of autonomic generation of EEG rhythms at the cortical level are discussed as putative mechanisms of dissociation of EEG activities in visual cortex and thalamus.