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  • 1
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cathodoluminescence and fluorescence microscopy have been used to study vasogenic edema in experimentally induced brain tumors in rats. Both methods are suited for the demonstration of FITC- or TRITC-coupled antiserum, and thus allow the evaluation of serum protein extravasation. Cathodoluminescence is more time consuming and laborious than fluorescence microscopy, but it has distinct advantages: Contrast enhancement improves the differentiation between certain cell types, and the higher resolution of the scanning electron microscope allows the identification of subcellular regions which cannot be recognized by conventional fluorescence microscopy.
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  • 2
    ISSN: 1432-1238
    Keywords: Key words Brain resuscitation ; Cardiac arrest ; Cerebral ischemia ; Microcirculation ; Thrombolytic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Successful resuscitation of the brain requires complete microcirculatory reperfusion, which, however, may be impaired by activation of blood coagulation after cardiac arrest. The study addresses the question of whether postischemic thrombolysis is effective in reducing cerebral no-reflow phenomenon. Design: 14 adult normothermic cats were submitted to 15-min cardiac arrest, followed by cardiopulmonary resuscitation (CPR) and 30 min of spontaneous recirculation. The CPR protocol included closed-chest cardiac massage, administration of epinephrine 0.2 mg/kg, bicarbonate 2 mEq/kg per 30 min, and electrical defibrillation shocks. Interventions: During CPR, animals in the treatment group (n=6) received intravenous bolus injections of 100 U/kg heparin and 1 mg/kg recombinant tissue type plasminogen activator (rt-PA), followed by an infusion of rt-PA 1 mg/kg per 30 min. Measurements and results: Microcirculatory reperfusion of the brain was visualized by labeling the circulating blood with 300 mg/kg of 15% fluorescein isothiocyanate albumin at the end of the recirculation period. Areas of cerebral no-reflow – defined as the absence of microvascular filling – were identified by fluorescence microscopy at eight standard coronal levels of forebrain, and expressed as the percentage of total sectional area. One animal in the treatment group was excluded from further analysis because of intracerebral hemorrhage due to brain injury during trepanation. Autopsy revealed the absence of intracranial, intrathoracic, or intra-abdominal bleeding in all the other animals. In untreated animals (n=8), no-reflow affected 28±13% of total forebrain sectional areas, and only 1 out of 8 animals showed homogenous reperfusion (i.e., no-reflow 〈15% of total forebrain sectional areas). Thrombolytic therapy (n=5) significantly reduced no-reflow to 7±5% of total forebrain sectional areas and all treated animals showed homogeneous reperfusion at the microcirculatory level. Conclusions: The present data demonstrate that thrombolytic therapy improves microcirculatory reperfusion of the cat brain when administered during reperfusion after cardiac arrest.
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  • 3
    ISSN: 1432-1238
    Keywords: Cardiopulmonary bypass ; Extracorporeal circulation ; Cerebrovascular circulation ; Energy metabolism ; Electroencephalogram ; Evoked potentials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective Recently, extracorporeal life support (ECLS) by venoarterial bypass perfusion has been recommended for the treatment of refractory respiratory and/or cardiac failure but the safety of this application for the brain is not yet established. Therefore, the effects of normothermic ECLS on cerebral blood flow, metabolism and electrophysiology were studied in cats with total arrest of cardiopulmonary circulation. Design An extracorporeal circulation (ECC) system, consisting of a roller pump, a membrane oxygenator and a heat exchanger, was connected to the circulation of cat by cannulae inserted via the jugular vein and femoral vessels. After 2 h ECLS brains were frozen in situ and investigated for changes in regional metabolism. Measurements and results During 2 h ECC hematocrit declined from 37±7% to 21±10% (means±SD,p〈0.05), cerebral blood flow decreased to 73±14% of control (p〈0.05) and cerebral oxygen delivery to 46±13% of control (p〈0.05) although arterial blood pressure and bypass flow rate did not change. Plasma lactate increased from 0.8±0.3 to 9.2±4.2 μmol/ml (p〈0.05), and brain tissue lactate from 2.3±0.9 to 10.6±2.7 μmol/g (p〈0.05). Hematocrit correlated positively with cerebral oxygen delivery (r=0.86,p〈0.001). Conclusions These data demonstrate that ECLS is associated with reduced cerebral oxygen delivery and may cause brain hypoxia despite normal blood pressure. This complication may contribute to the high incidence of neurological disturbances after prolonged ECLS.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 21 (1995), S. 132-141 
    ISSN: 1432-1238
    Keywords: Brain resuscitation ; Cardiac arrest ; Cerebral ischemia ; Closed chest cardiac massage ; Microcirculation ; No-reflow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective Successful resuscitation of the brain requires unimpaired blood recirculation. The study addresses the question of the severity and reversibility of no-reflow after cardiac arrest. Design Adult normothermic cats were submitted to 5, 15 and 30 min cardiac arrest by ventricular fibrillation. The extent of no-reflow was assessed in each cardiac arrest group after 5 min closed chest cardiac massage in combination with 0.2 mg/kg epinephrine or after successful resuscitation followed by 30 min recirculation. Measurements and results Reperfusion of the brain was visualized by labelling the circulating blood with FITC-Albumin. Areas of no-reflow, defined as absence of microvascular filling, were identified by fluorescence microscopy at 8 standard coronal levels of forebrain, and expressed as percent of total sectional area. During cardiac massage, noreflow affected 21±5%, 42±38% and 70±27% of forebrain after 5, 15 and 30 min cardiac arrest, respectively. After 30 min spontaneous recirculation following successful resuscitation of the heart, no-reflow significantly declined to 7±11% after 5 min cardiac arrest (p〈0.05) but persisted in 30±11% and 65±21% of forebrain after 15 and 30 min cardiac arrest, respectively (n.s.). Conclusion Our observations demonstrate that resuscitation of the heart by closed chest massage causes severe (and after prolonged cardiac arrest irreversible) no-reflow of the brain. This suggests that no-reflow is an important cause of postresuscitation brain pathology.
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  • 5
    ISSN: 1432-1238
    Keywords: Isovolemic hemodilution ; Brain tissue ATP ; Brain tissue pH ; Brain tissue lactate ; Cats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective It has been established that during constant presure arterio-venous bypass perfusion, brain metabolism gradually deteriorates in parallel with the declining hematocrit. However, whether this is due to a disturbance of flow regulation or to the decline in the oxygen-carrying capacity of the blood has not been documented. Therefore, intact animals were submitted to severe hemodilution to determine the threshold for the beginning of functional and biochemical impairment of the brain. Methods Six anesthetized and paralyzed adult mongrel cats were submitted to gradual isovolemic hemodilution by stepwise exchange of blood with Ringer lactate/dextran (1∶1) solution. Exchange of 80 ml/kg body weight resulted in a final hematocrit level ranging from 6.1% to 11%. Results Cerebral blood flow gradually increased during hemodilution, with a sharp rise to eight times the prehemodilution value when the hematocrit fell below 10%. The calculated oxygen delivery to the brain remained relatively unchanged. Hemodilution did not cause suppression of spontaneous ECoG or somatically evoked primary cortical potentials, even at the lowest hematocrit value of 6.1%. Brain tissue ATP and phosphocreatine content were largely maintained, although tissue lactate content was elevated (9.54±5.99 μmol/g). Conclusions The hemodynamically unimpaired healthy mammal is able to support a substantial degree of hemodilution without major functional or biochemical disturbance to the brain. The previously observed disturbances during prolonged bypass perfusion are, therefore, most probably due to the associated abnormalities of flow regulation.
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  • 6
    ISSN: 1432-1106
    Keywords: Reticular formation ; Convergence ; Inhibition ; Cat ; Chloralose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Ein konditionierender corticaler Reiz inhibiert den somatischen Startlereflex bei Katzen unter Chloralosenarkose für eine Dauer von mehr als 200 ms. Die Interaktionen zwischen beiden Reizen laufen in der bulbären und pontinen Formatio reticularis ab. 2. Dem Startlereflex liegt eine polysynaptische Erregungsschleife zugrunde, die die bulbäre und pontine Formatio reticularis durchzieht. Die Resistenz der reticulären Neurone gegenüber repetitiver Stimulation wurde als Kriterium ihrer funktionellen Lokalisation auf dem polysynaptischen Reflexbogen gewertet. 3. Die corticale Inhibition wird im Verlaufe der polysynaptischen Erregungsschleife zunehmend stärker. Neurone, die von den Startlereflexafferenzen direkt erregt werden, werden durch den corticalen Reiz nicht inhibiert. Dies schliebt eine präsynaptische Inhibition der reticulopetalen Fasersysteme aus.
    Notes: Summary 1. The startle reflex evoked by cutaneous stimulation in cats under chloralose anesthesia is inhibited for more than 200 ms by a conditioning cortical volley. The interaction between the cutaneous and the cortical volley takes place in the bulbar and pontine reticular formation. 2. The startle reflex involves a series of reticular neurones. Resistance to repetitive stimulation has been determined to evaluate the functional localization of each neurone within this polysynaptic path. 3. Inhibition following the cortical volley becomes increasingly more effective along the course of the polysynaptic path and is completed within 5–6 ms. Reticular neurones excited directly by the spino-reticular afferents are not inhibited, thus excluding a presynaptic inhibition of the spinoreticular fibres.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 45 (1979), S. 195-203 
    ISSN: 1432-0533
    Keywords: Brain edema ; Blood flow ; Peritumorous edema ; Encephalography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 23 cats, vasogenic brain edema was produced by stereotaxic xenotransplantation of the glial cell clone RG 2 into the internal capsula of the brain. The resulting tumor grew to a diameter of 0.5–1 cm within 2–3 weeks; thereafter it was either rejected, or the animal died. One to 4 weeks after the implantation, the EEG, intracranial pressure, and blood flow were recorded using labelled microspheres. The permeability of the blood-brain barrier was tested with Evans blue, and the animal was subsequently killed by air embolism. Tissue samples were taken from peritumorous and contralateral white and grey matter, and assessed for water and electrolyte content, and blood flow. Adjacent sections were fixed in formalin and investigated for permeability disturbances of the blood-brain barrier, and for the spread of peritumorous edema by tracing intracerebral serum albumins with a specific immunofluorescent technique. Permeability disturbances of the blood-brain barrier were restricted to the tumor, but there was, after 2 weeks, massive leakage of serum albumins into the surrounding white matter. Water content in the peritumorous white matter increased from 69.1±0.9 to more than 80%, reaching a maximum after 2–3 weeks. Sodium content rose from 163 to 390 meq/kg d.w., whereas potassium remained almost constant. Blood flow in the edematous white matter was markedly reduced from 32.2±5.6 to 16.5±1.4 ml/100 g/min after 4 weeks. The decrease was due to the expansion of tissue volume and not to an increase in vascular resistance. Fourier transform of the EEG revealed a significant slowing of the mean frequency on the affected side in 6 out of 13 animals. There was no consistent correlation with either the duration of survival, the water content, electrolyte shifts, blood flow or intracranial pressure. EEG changes, in consequence, seem to result from direct influence of the tumor on brain parenchyma, rather than from peritumorus edema or intracranial hypertension.
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  • 8
    ISSN: 1432-0533
    Keywords: Experimental brain tumor ; Brain edema ; Horseradish peroxidase ; Serum protein extravasation ; Corticosteroid therapy ; Cats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental brain tumors were produced in 20 cats by stereotaxic xenotransplantation of a blastomatous glial cell clone into the internal capsule of the left hemisphere. Ten of these animals were treated after 2 weeks with a single injection of 10 mg dexamethasone in crystalline suspension. Three weeks after xenotransplantation vascular permeability was studied by electron microscopy with horseradish peroxidase as the barrier tracer (four animals), and extravasation of serum proteins was visualized by immunohistochemistry, using an image processing system (16 animals). In animals used for immunohistochemistry, the water content of peritumoral brain tissue was also determined. In both treated and untreated animals, spherical tumors with a diameter of about 10 mm were present at the implantation site. Extravasation of horseradish peroxidase was detected only in the tumor, but there was accumulation of serum proteins both in the tumor and the peritumoral white matter. Edema, in consequence, originated mainly in the tumor from where it spread into the surrounding brain tissue. Corticosteroid therapy reduced the water content of peritumoral brain tissue but did not affect increased barrier permeability of tumor vessels, and only slightly improved peritumoral accumulation of serum proteins. It is concluded that amelioration of tumor edema by corticosteroids cannot result solely from tightening of the blood-brain barrier to circulating macromolecules but must be due to an active restoration of cerebral water homeostasis despite persisting serum protein extravasation.
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  • 9
    ISSN: 1432-0533
    Keywords: Gerbil ; Pentobarbital ; Morphometry ; Selective vulnerability ; Ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Mongolian gerbils were subjected to bilateral carotid occlusion for 5 and 10 min, followed by 7 days of recirculation. After this interval, serial sections were made of the posterior region of the dorsal hippocampus, and the number of surviving neurons was determined per mm length of CA1 sector. In halothane-anesthetized animals only 21.1% of CA1 neurons survived 5-min ischemia, but this percentage could be raised to 78.6% when animals were pretreated with 25 mg/kg pentobarbital before ischemia. Pretreatment with 50 mg/kg pentobarbital before 5-min ischemia or pretreatment with 25 mg/kg pentobarbital before 10-min ischemia did not reduce CA1 lesions. It is concluded that a non-anesthetic dose of barbiturates is able to prevent selective vulnerability of CA1 sector, but that this effect is limited to the initial 5 min of ischemia.
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  • 10
    ISSN: 1432-0533
    Keywords: Brain tumors ; Rats ; Blood flow ; Metabolism ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental brain tumors were produced in rats by stereotactical implantation of various neoplastic cell lines (RG 2, RGl 2.2, G 13/11, F 98, RN 6, B 104, and E 367). Using autoradiographic, bioluminescence, and fluoroscopic methods, the following regional hemodynamic and metabolic parameters were measured on intact brain sections: blood flow, glucose utilization, pH, and the tissue content of ATP, glucose, and lactate. Tumors exnhibited a considerable diversity of regional blood flow and metabolic activity which did not correlate with the implanted cell line, location, or growth pattern. In solid regions of tumors the most consistent finding was a higher glucose utilization rate, a higher lactate, and a higher pH than in the surrounding brain tissue. Tumor ATP was slightly higher and glucose sightly lower than in the brain. In large spherical tumors a declining gradient of blood flow, glucose, and ATP from the periphery to the central parts was frequently observed, the decline being more pronounced for glucose than for ATP. In regions with high ATP tissue pH was usually higher than in the brain, but it decreased in areas in which ATP was depleted. The results obtained indicate that tumors are able to control tissue pH despite increased glycolysis and lactate production, as long as the energy state is not impaired. The mechanisms of pH regulation, therefore, have to be considered for establishing therapeutic procedures which intend to lower tumor pH for induction of tissue necrosis.
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