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  • 1
    ISSN: 1432-0533
    Keywords: Cerebral hypoxia ; Cerebral ischemia ; Ultrastructure ; Neocortex ; Brain isolation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The acute cortical response to surgical brain isolation and subsequent extracorporal normoxic or 30 min hypoxic (PaO2=20 mm Hg) perfusions (hypoxic hypoxia with relative ischemia) was evaluated. Cerebral blood flow, arterial pH and CO2 were maintained constant during both perfusions; only the arterial oxygen content was changed. The isolated brain model used in this and previous investigations produces no qualitative ultrastructural changes in the neocortex following brain isolation and normoxic perfusion. However, the acute cortical structural response to 30 min of hypoxic hypoxia with relative ischemia demonstrated a number of important observations. Hypoxic hypoxia produced ultrastructural responses common to cerebral ischemia such as nuclear chromatin clumping, nucleolar condensation and cytoskeletal breakdown. Although neuronal abnormalities seen after 30 min of hypoxic hypoxia were similar to those acute neuronal changes observed following complete cerebral ischemia without recirculation, they differed three ways: (a) mitochondrial swelling and microvacuolation were observed in many cortical pyramidal neurons. (b) Glycogen particles within astroglial processes were observed even after a 30-min period of hypoxic hypoxia. (c) Perivascular astroglial swelling was minimal despite considerable perineuronal swelling. In contrast, incomplete cerebral ischemia produces mitochondrial changes similar to those in hypoxic hypoxia but also causes the depletion of tissue glycogen and perivascular glial swelling. Thus, hypoxic hypoxia with relative ischemia produces a unique acute ultrastructural response compared to either complete or incomplete cerebral ischemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We have studied the metabolic and functional effects of two new platelet-activating factor (PAF) antagonists (BN 50726 and BN 50739) and their diluent (dimethyl sulfoxide; DMSO) during reoxygenation of the 14-min ischemic isolated brain. Blood gases, EEG, auditory evoked potentials, cerebral metabolic rate for glucose (CMRglc), and cerebral metabolic rate for oxygen (CMRO2) were monitored throughout the study. Frozen brain samples were taken for measurement of brain tissue high-energy phosphates, carbohydrate content, and thiobarbituric acid-reactive material (TBAR, an indicator of lipid peroxidation) at the end of the study. Following 60 min of reoxygenation in the nontreated 14-min ischemic brains, lactate, AMP, creatine (Cr), intracellular hydrogen ion concentration [H+]i), and TBAR values were significantly higher and ATP, creatine phosphate (PCr), CMRglc, CMRO2, and energy charge (EC) values were significantly lower than the corresponding normoxic control values. PCr and CMRO2 values were significantly higher, and glycogen, AMP, and [H+]i values were significantly lower in the BN 50726-treated ischemic brains than in DMSO-treated ischemic brains. In brains treated with BN 50739, ATP, ADP, PCr, CMRO2, and EC values were significantly higher, and lactate, AMP, Cr, and [H+]i values were significantly lower than corresponding values in the DMSO-treated ischemic brains. TBAR values were near control levels in all brains exposed to DMSO. There was also marked recovery of EEG and auditory evoked potentials in brains treated with DMSO. Treatment with BN 50726 or BN 50739 in DMSO appeared to improve brain mitochondrial function and energy metabolism partly as the result of DMSO action as a free radical scavenger. The PAF antagonists act at a different level, possibly restoring normal mitochondrial function or preventing some of the adverse effects of increased excitatory amino acid and/or intracellular Ca2+ levels. This is the only drug combination currently known to promote such complete short-term metabolic and functional recovery during postischemic reoxygenation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 17 (1970), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Surgically isolated canine brains were maintained with compatible donor blood from an extracorporeal perfusion system. Small samples of frozen cerebral cortex were removed with a newly-developed Freon cryoprobe and were analysed for acid-soluble nucleotides, creatine phosphate and inorganic phosphate. Most animals were in the early stages of shock unless they had received preoperative α-adrenergic blockade with phenoxybenzamine hydrochloride (Dibenzyline). Values for high-energy phosphates were in the normal range only when the animal had been premedicated with phenoxybenzamine hydrochloride. During a 4-min period of anoxia (induced by blood which had been equilibrated with 95% N2 and 5% CO2), the cerebral cortex rapidly became iso-electric, and the levels of creatine phosphate and ATP decreased concomitantly with increases in levels of ADP and Pi. These electrical and chemical changes were rapidly and completely reversed by reoxygenation. The levels of high-energy phosphates provide a sensitive criterion of functional adequacy that may be more readily quantitated than cerebral electrical activity (EEG). EEG recovery did not correlate closely with rephosphorylation.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 72 (1999), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : A unique method for simultaneously measuring interstitial(pHe) as well as intracellular (pHi) pH in the brains oflightly anesthetized rats is described. A 4-mm microdialysis probe wasinserted acutely into the right frontal lobe in the center of the area sampledby a surface coil tuned for the collection of 31P-NMR spectra.2-Deoxyglucose 6-phosphate (2-DG-6-P) was microdialyzed into the rat until asingle NMR peak was detected in the phosphomonoester region of the31P spectrum. pHe and pHi values werecalculated from the chemical shift of 2-DG-6-P and inorganic phosphate,respectively, relative to the phosphocreatine peak. The average in vivopHe was 7.24 ± 0.01, whereas the average pHi was7.05 ± 0.01 (n = 7). The average pHe value and the averageCSF bicarbonate value (23.5 ± 0.1 mEq/L) were used to calculate aninterstitial Pco2 of 55 mm Hg. Rats were then subjected to a 15-minperiod of either hypercapnia, by addition of CO2 (2.5, 5, or 10%)to the ventilator gases, or hypocapnia (Pco2 〈 30 mm Hg), byincreasing the ventilation rate and volume. pHe responded inverselyto arterial Pco2 and was well described (r2 =0.91) by the Henderson-Hassel-balch equation, assuming apKa for the bicarbonate buffer system of 6.1 and asolubility coefficient for CO2 of 0.031. This confirms the viewthat the bicarbonate buffer system is dominant in the interstitial space.pHi responded inversely and linearly to arterial Pco2.The intracellular effect was muted as compared with pHe (slope =-0.0025, r2 = 0.60). pHe and pHivalues were also monitored during the first 12 min of ischemia produced bycardiac arrest. pHe decreases more rapidly than pHiduring the first 5 min of ischemia. After 12 min of ischemia, pHeand pHi values were not significantly different (6.44 ± 0.02and 6.44 ± 0.03, respectively). The limitations, advantages, and futureuses of the combined microdialysis/31P-NMR method for measurementof pHe and pHi are discussed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 227 (1970), S. 409-409 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] To determine whether sensory responses can be evoked in the isolated dog brain, four dogs anaesthetized with methoxyfluorine were prepared in the usual manner1'2. In two of the dogs a small amount of tissue was left on the snout to permit mechanical stimulation of the skin. The structures of the ...
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-6903
    Keywords: Intracellular pH ; extracellular pH ; 31P-MRS ; pH regulation ; ischemia ; hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the last decade, significant progress has been made in the characterization of pH regulation in nervous tissue in vitro. However, little work has been directed at understanding how pH regulatory mechanisms function in vivo. We are interested in how ischemic acidosis can effect pH regulation and modulate the extent of post-ischemic brain damage. We used 31P-MRS to determine normal in vivo pHi and pHe simultaneously in both the isolated canine brain and the intact rat brain. We observed that the 31Pi peak in the 31P-MRS spectrum is heterogeneous and can be deconvoluted into a number of discrete constituent peaks. In a series of experiments, we identified these peaks as arising from either extracellular or intracellular sources. In particular, we identified the peak representing the neurons and astrocytes and showed that they maintain different basal pH (6.95 and 7.05, respectively) and behave differently during hypoxic/ischemic episodes.
    Type of Medium: Electronic Resource
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