bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE APPEARANCE OF REGIONAL VARIATIONS IN METABOLISM AT A CRITICAL LEVEL OF DIFFUSE CEREBRAL OLIGEMIA
Authors: Welsh F. A. , Durity F. , Langfitt T. W. 
Published: October 2006

Abstract—Increased intracranial pressure was used to produce graded cerebral oligemia in the rabbit. When cerebral perfusion pressure (CPP) was 40 Torr or above, oligemia was not severe enough to cause a decrease in ATP. When CPP was 20 Torr or below, a rapid depletion of ATP occurred. When CPP equalled 30 Torr, animals were distributed at the two extremes, with pronounced diminution of ATP correlating with loss of electrical activity and with increased NADH tissue fluorescence. In addition this critical stage of oligemia was marked by the appearance of regional variations in metabolism. Furthermore, ischemic regions could be visualized in sections of frozen brain by virtue of increased NADH fluorescence.
THE EFFECT OF ISCHAEMIA AND RECIRCULATION ON PROTEIN SYNTHESIS IN THE RAT BRAIN
Authors: Cooper Helen K. , Zalewska Teresa , Kawakami S. , Hossmann K.‐A. , Kleihues P. 
Published: October 2006

Abstract— Rats were subjected to cerebral compression ischaemia for 15min and were subsequently recirculated with blood for periods up to 3 h. In vivo incorporation of intravenously administered L‐[1–14C]valine into total brain proteins was found to be severely inhibited (about 20% of controls) after 45 min of recirculation. After 3 h, protein synthesis had increased, the specific radioactivity of proteins then being about 40% of controls. The post‐ischaemic inhibition of protein synthesis was accompanied by a breakdown in polyribosomes and a concomitant increase in ribosomal subunits. In vitro incorporation of L‐[1–14C]phenylalanine by a postmitochondrial supernatant system derived from animals subjected to 15 min ischaemia and 15 min recirculation was also severely reduced and showed, in contrast to control animals, no response to the addition of a specific inhibitor of polypeptide chain initiation (Poly(I)). Together with the in vivo accumulation of ribosomal subunits this indicates a block in peptide chain initiation during the early stages of recirculation.Polyribosomes from animals subjected to 15 min ischaemia without recirculation showed a normal rate of in vitro protein synthesis which was inhibited by Poly(I) to a similar extent as polyribosomes from control animals. These results suggest that the post‐ischaemic inhibition in chain initiation develops during the early stages of recirculation rather than during the ischaemic period itself.
CEREBRAL METABOLIC AND VASCULAR EFFECTS OF BARBITURATE THERAPY FOLLOWING COMPLETE GLOBAL ISCHEMIA
Authors: Steen P. A. , Milde J. H. , Michenfelder J. D. 
Published: October 2006

AbstractComplete global cerebral ischemia was induced in dogs by temporary ligation of the ascending aorta for 10min. Prior to the ischemic period, half of the animals were given pentobarbital 30‐38 mg/kg, a maneuver previously reported to prevent or attenuate cerebral damage in this same model. Cerebral blood flow (CBF) and cerebral metabolic rate (CMRO2) were followed from prior to the ischemic period to 6 h post‐ischemia. At varying time intervals following ischemia, brain biopsies were obtained and analyzed for cerebral metabolites to determine the cerebral energy state. Only a few differences were observed between pentobarbital‐treated and untreated animals. Post‐ischemic CMRO2, stabilized at a significantly lower level in treated than in untreated animals. However, CBF was proportionately lower and thus O2 delivery relative to O2 needs in the two groups was comparable. Also in both groups, the CBF and CMRO2 stabilized at levels significantly below pre‐ischemia controls. Cerebral energy stores in both groups were depleted after 10min of ischemia but were restored to near normal within 4min post‐ischemia. Total restoration of the adenine nucleotide pool and ATP were delayed as was the return of brain lactate to normal. A 10min period of post‐ischemic hyperemia was observed in all animals and in the initial 4min post‐ischemia CMRO2 was also increased. The latter is probably accounted for by the O2 needs for restoration of cerebral energy and O2 stores. We conclude that cerebral protection as provided by barbiturates following complete global ischemia cannot be accounted for by any measurable effect on CBF, CMRO2, or the cerebral energy stores during the initial 6 h post‐ischemia.
LYSINE METABOLISM IN THE RAT BRAIN: THE PIPECOLIC ACID‐FORMING PATHWAY
Authors: Chang Yung‐Feng 
Published: October 2006

Abstract—Employing both the intraventricular and intraperitoneal injection techniques, 14C‐l‐lysine at non‐overloading concentrations was found to be metabolized to l‐14C‐pipecolic acid at significantly high levels in the rat. Labeled pipecolic acid in the brain and liver was only found at rather low levels 24 h after intraperitoneal administration of 14C‐l‐lysine regardless of non‐labeled lysine metabolite overload. A marked enhancement of pipecolic acid labeling was only found in the brain when 14C‐l‐lysine was intraventricularly administered to animals under various lysine metabolite overloads. While overloading doses of non‐labeled saccharopine or α‐aminoadipate did not significantly alter the labeling patterns of pipecolic acid in the brain, liver or urine when 14C‐l‐lysine was intraperitoneally administered, pipecolate overloading markedly reduced labeled pipecolic acid levels in the brain, liver and urine. These results indicate: pipecolic acid formation is subject to product inhibition, and saccharopine is not in the pathway of pipecolic acid synthesis from l‐lysine. The labeling pattern of lysine metabolites was not significantly affected by the overloading injection of pipecolic acid when 14C‐l‐lysine was intraventricularly administered suggesting a blood‐brain barrier for pipecolate. Besides 14C‐pipecolic acid, labeled α‐aminoadipic acid was also found at significant levels mostly in the brain. Labeled saccharopine was not detected in any tissues or urine samples analyzed. The 14C‐l‐lysine metabolic pattern of the newborn rats did not seem to be any different from the adult rats, i.e. labeled pipecolic acid was also detected in substantial quantities in the brain, liver and urine 5 h after injection. 14C‐d‐Lysine was mainly metabolized to l‐14C‐pipecolic acid through either route of administration. These experimental evidences indicate that the pipecolic acid‐forming pathway is a significant route for lysine metabolism in the rat, and that the rat brain probably utilizes this pathway mainly for lysine metabolism. The present study also discusses the potential neurological significance of the pipecolic acid pathway in relation to the major lysine metabolic pathway (the saccharopine pathway).
EFFECTS OF OSMOLAR CHANGES ON ISOLATED MITOCHONDRIA OF BRAIN AND LIVER
Authors: Holtzman D. , Lewiston N. , Herman M. M. , Desautel M. , Brewer E. , Robin E. 
Published: October 2006

Abstract— The effects of altered osmolarity on respiration and fine structure were compared in isolated rat cerebral versus liver mitochondria.Polarographic study of cerebral mitochondria in hypo‐osmolar media showed inhibition of State 3 (ADP‐dependent) respiration which was not reversed by dinitrophenol. In hyperosmolar media, State 3 respiration was transiently inhibited and State 4 (ADP‐independent) respiration increased with the NAD‐linked substrate pair, glutamate and malate. With succinate as substrate, respiration was not affected by moderate hyperosmolarity. In the most hyperosmolar medium, State 3 respiration was inhibited with both substrates.In contrast to the results with cerebral mitochondria, State 4 respiration was increased in hypo‐osmolar media and State 3 respiration was persistently inhibited in hyperosmolar media in liver mitochondria with both substrates.In both cerebral and liver mitochondria, cytochrome c oxidase (EC 1.9.3.1.) activity was mildly inhibited in hypo‐osmolar media and increased in hyperosmolar media.Electron microscopy showed that liver mitochondria were swollen in hypo‐osmolar media and condensed in hyperosmolar media. Cerebral mitochondria showed mild rarefaction in hypo‐osmolar media and, in hyperosmolar media, more than half the mitochondria showed either no or minimal changes in fine structure.Our results suggest that there are differences in metabolic control and structure between mitochondria from different cell types, which may be important in the cellular metabolic response to pathologic changes in water or osmolarity.
UNILATERAL BRAIN INJURY IN THE RABBIT; REVERSIBLE AND IRREVERSIBLE DAMAGE OF THE MEMBRANAL ATPases
Authors: Rigoulet M. , Guerin B. , Cohadon F. , Vandendreissche M. 
Published: October 2006

Abstract—Modifications of some membranal enzymatic activities in rabbit brain edema induced by cold injury were studied. The edema was characterized by the tissue H2O content and the K+/Na+ ratio. Comparison of the respiratory rate of isolated mitochondria in the state 3 and 4 and the ADP/O ratio suggested an alteration in the ATP synthesis mechanism. The oligomycin sensitive ATPase activity was severely reduced in mitochondria isolated from edematous cells.The alteration of the ouabain sensitive Na+‐K+‐ATPase was first qualitative in the sense where the response of the ATPase to the K+/Na+ ratio was modified. A loss of the total activity was then observed. Intravenous injection of CDP choline induced a regression of the edema, a restoration of the sensitivity of the mitochondrial ATPase towards oligomycin and a restoration of the sensitivity of the Na+‐K+‐ATPase to the K+/Na+ ratio. These results suggest that the reversible damages of the cells induced by cold injury were due to a disorder at the protein‐lipid interaction level.
EFFECT OF DRUGS ON RAT BRAIN, CEREBROSPINAL FLUID AND BLOOD GABA CONTENT
Authors: Ferkany John W. , Butler Ian J. , Enna S. J. 
Published: October 2006

AbstractAcute administration of GABA transaminase inhibitors to rats results in a dose‐dependent increase in both brain and blood GABA content and administration of isonicotinic acid hydrazide (INH), at a dose which decreases the amount of brain GABA, also lowers blood levels of this amino acid. Chronic treatment (10 days) with INH (20mg/kg), y‐acetylenic‐GABA (10 mg/kg) or aminooxyacetic acid (AOAA) (10 mg/kg) results in a significant elevation in both rat brain and blood GABA concentrations. At the doses studied, only AOAA caused a significant elevation in CSF GABA content. Co‐administration of pyridoxal phosphate (2 mg/kg) blocks the chronic INH‐induced rise in blood GABA but does not affect the increase in brain content of this amino acid. Chronic administration of di‐n‐propylacetate (20 mg/kg) did not significantly alter brain, blood or CSF GABA levels. The results suggest that, under the proper conditions, changes in blood GABA levels after administration of inhibitors of GABA synthesis or degradation may be an indirect indicator of changes in the brain content of this amino acid. Blood GABA determinations may be useful for studying the biochemical effectiveness of GABA transaminase inhibitors in man.
γ‐Hydroxybutyrate: Cerebral Metabolic, Vascular, and Protective Effects
Authors: Artru Alan A. , Steen Petter A. , Michenfelder John D. 
Published: October 2006

Abstract:The cerebral protection afforded by each of several preparations of γ‐hydroxybutyrate (GHB) was examined in the hypoxic (Fio2= 0.05) mouse model. The greatest increase in survival time (85%) occurred after prereatment with 300 mg/kg given as buffered β‐butyrolactone (GBL). Compared with previous studies employing the same hypoxic model, this increase was less than that observed with certain barbiturates and equal to that observed with certain anesthetics. The cerebral and systemic metabolic and vascular effects of each of several preparations of GHB were examined in a canine model. The cerebral metabolic rate for oxygen (CMRo2) tended to increase after GHB 100 mg/kg, then progressively decreased after cumulative doses of 600 mg/kg and 1100 mg/kg. The greatest depression in CMRo2 (48%) occurred with 1100 mg/kg given as unbuffered GBL. With each preparation and at every dose, a reduction in cerebral blood flow (CBF) exceeded the reduction in CMRo2 The major systemic effect was an almost two‐thirds reduction in cardiac output at the largest doses. Assuming no species difference the cerebral protection observed with GHB is probably limited by both the reduction in cardiac output and the unfavorable relationship of cerebral oxygen supply to demand (CBF/CMRo2). Brain biopsies taken after the cumulative dose of GHB 1100 mg/kg showed a trend toward lower phosphocreatine levels and higher lactate and lactate/pyruvate levels than in untreated dogs.
Glutathione and Ascorbate During Ischemia and Postischemic Reperfusion in Rat Brain
Authors: Cooper Arthur J. L. , Pulsinelli William A. , Duffy Thomas E. 
Published: October 2006

Abstract:Thirty minutes of total cerebral ischemia (decapitation) decreased total glutathione (GSH + GSSG) by 7% but had no detectable effect on the concentration of oxidized glutathione (GSSG), reduced ascorbate, or total ascorbate. In a model of reversible, bilateral hemispheric ischemia (four‐vessel occlusion) no changes in glutathione or ascorbate were detected after 30 min of ischemia. During 24 h of reperfusion following such an insult no detectable change in total ascorbate, reduced ascorbate, or oxidized glutathione was noted; however, total brain glutathione declined by 25%. The findings are discussed in relation to the hypothesis that the deleterious effects of ischemia are due to an increase in free radical production which in turn leads to increased lipid peroxidation.
δ‐Aminolaevulinic Acid Uptake, Toxicity, and Effect on [14C]γ‐Aminobutyric Acid Uptake into Neurons and Glia in Culture
Authors: Percy V. A. , Lamm M. C. L. , Taljaard J. J. F. 
Published: October 2006

Abstract:δ‐Aminolaevulinic acid (ALA) uptake into neurons and glia in primary culture as well as ALA toxicity and its effects on γ‐aminobutyric acid (GABA) uptake were examined. [4‐14C]ALA uptake into neurons and glia was nonsaturable, partially Na+‐ and temperature‐dependent, and appeared to comprise mainly diffusion into the cell. 2,4‐Dinitrophenol caused some inhibition of [4‐14C]ALA uptake whereas ouabain, KCN, or amino acids at 1 mM concentration were without effect. ALA (1 mM) caused a slight inhibition of [U‐14C]GABA uptake into neurons (14%) and glia (9%), but was without effect at lower concentrations. It is unlikely that, in acute porphyria, ALA reaches sufficiently high levels in nervous tissue to interfere with the reuptake of GABA into neurons or glia. ALA was shown to be toxic, judged by the loss of cells, to both neurons and glia at concentrations as low as 10 μM. Such a concentration of ALA may be expected to occur in the CSF of porphyric patients in the acute attack. However, results obtained with dispersed cells in culture may not necessarily reflect the situation in vivo where the cell may have a far greater resistance to the effects of toxic agents.
BAY K 8644, a 1,4‐Dihydropyridine Ca2+ Channel Activator: Dissociation of Binding and Functional Effects in Brain Synaptosomes
Authors: Rampe D. , Janis R. A. , Triggle D. J. 
Published: October 2006

AbstractK+‐stimulated 45Ca2+ uptake into rat brain and guinea pig cerebral cortex synaptosomes was measured at 10 s and 90 s at K+ concentrations of 5–75 mM. Net increases in 45Ca2+ uptake were observed in rat and guinea pig brain synaptosomes. 45Ca2+ uptake under resting or depolarizing conditions was not increased by the 1,4‐dihydropyridine BAY K 8644, which has been shown to activate Ca2+ channels in smooth and cardiac muscle. High‐affinity [3H]nitrendipine binding in guinea pig synaptosomes (KD= 1.2 × 10‐10M, Bmax= 0.56 pmol mg‐1 protein) was competitively displaced with high affinity (IC50, 2.3 × 10‐9M) by BAY K 8644. Thus high‐affinity Ca2+ channel antagonist and activator binding sites exist in synaptosome preparations, but their relationship to functional Ca2+ channels is not clear.
Effects of Antimycin, Glucose Deprivation, and Serum on Cultures of Neurons, Astrocytes, and Neuroblastoma Cells
Authors: Pauwels Petrus J. , Opperdoes Fred R. , Trouet André 
Published: October 2006

Abstract:The resistance of cultured mouse neuroblastoma cells, primary cultures of rat cerebellar neurons, and rat brain astrocytes to a block of aerobic metabolism was studied. Parameters such as lactate production and ATP content were measured in the presence of antimycin A and under various conditions of glucose, oxygen, and serum supply. The following conclusions can be drawn: (1) All cell types studied were characterized by an active production of lactate; (2) Incubation of the various cell types in the absence of glucose at normal oxygen tension did not affect ATP levels; (3) Respiration blocked by antimycin led to a Pasteur effect; (4) Neuroblastoma cells, but not the other cell types, were fully resistant to inhibition of respiration provided that sufficient glucose was supplied; (5) In the absence of glucose no stores of energy or utilizable substrate were present in the cell types studied when respiration was blocked; (6) In the presence of fetal calf serum anoxic neurons showed irreversible signs of degeneration.
Regional Distribution and Characterization of Kinin in the CNS of the Rat
Authors: Kariya K. , Yamauchi A. , Sasaki T. 
Published: October 2006

Abstract:The distribution of kinin in the CNS of the rat, which was extracted with n‐butanol from an acidified homogenate, was determined using a bradykinin (BK) radioimmunoassay system. The immunoreactive kinin was widely distributed throughout the brain. The highest content was found in the pituitary gland (4,135 fmol BK Eq/g), followed by the medulla oblongata (912 fmol/g), cerebellum (549 fmol/g), and cortex (512 fmol/g). The kinin in the posterior pituitary was concentrated 4.5 times as much as in the anterior lobe. Serial dilution of brain extracts produced binding curves parallel to the standard radioimmunoassay curve. The purified brain kinin comigrated with authentic BK during CM‐cellulose chroma tography and Sephadex LH‐20 gel chromatography. Its molecular weight was estimated to be 1,127$45 by gel filtration, which coincides well with that of BK. Chymotrypsin degraded the extracted kinin and authentic BK, but trypsin did not. These data demonstrate that a peptide indistinguishable from BK exists in the rat brain. Furthermore, pituitary kinin was separated into BK (87%), Lys‐BK (10%), and Met‐Lys‐BK (3%), using reverse phase HPLC.
Rat Brain Mast Cells: Contribution to Brain Histamine Levels
Authors: Goldschmidt Robert C. , Hough Lindsay B. , Glick Stanley D. 
Published: October 2006

Abstract:Recent studies have shown that mast cells (MCs) are present in rat brain, that they have a predominantly thalamic localization, and that they contain histamine (HA). However, the degree to which these cells contribute to brain HA levels has remained unclear. Our recent studies of the precise distribution of rat brain MCs permitted us to develop a method to determine both the MC numbers and HA content from the same brain. Thalamic MC numbers were highly correlated with both the amount (ng) and the concentration (ng/g) of thalamic HA in both sexes (p < 0.005). Slopes of these regression lines, suggestive of the HA content of thalamic MCs, were 2.5 and 1.3 pg/cell in males and females, respectively, substantially less than the HA levels in peritoneal MCs. Thalamic MC numbers were not correlated with HA (ng) outside of thalamus, but were significantly (p < 0.005) correlated with whole brain HA amounts (ng) and levels (ng/g). These results are direct biochemical evidence for a contribution by MCs to brain HA levels, and indicate that thalamic MCs contribute up to 90% of the HA in thalamus, and up to 50% of whole brain HA levels.
Monoamine Oxidase in Rat and Bovine Endocrine
Authors: Lenzen Tissues Sigurd , Freisinger‐Treichel Marion , Panten Uwe 
Published: October 2006

Abstract:Monoamine oxidase (MAO) was characterized in tissue homogenates from rat pancreatic islets, rat neurohy‐pophysis and adenohypophysis, and rat and bovine adrenal medulla and adrenal cortex. Phenylethylamine was preferentially deaminated by rat pancreatic islet and bovine adrenal medulla MAO and with slight preference by rat neurohypophysis MAO, whereas 5‐hydroxytryptamine was preferentially deaminated by MAO from all other endocrine tissues. Tyramine was a good substrate for all tissues. Clor‐gyline, a selective inhibitor of MAO‐A, preferentially inhibited deamination of 5‐hydroxytryptamine by all tissue homogenates, whereas deprenyl, a selective inhibitor of MAO‐B, preferentially inhibited deamination of phenyl‐ethylamine. Km values for 5‐hydroxytryptamine and tyra‐mine were higher by one to two decimal powers than for phenylethylamine in homogenates from all endocrine tissues. Km values were significantly lower for 5‐hydroxytryptamine and significantly higher for phenylethylamine in rat and bovine adrenal cortex than in adrenal medulla. According to these results, the contributions of MAO‐B to total enzyme activity were 70% for rat pancreatic islets, 45% for rat neurohypophysis, 15% for rat adenohypophysis, 20% for rat adrenal medulla, 10% for rat adrenal cortex, 60% for bovine adrenal medulla, and 20% for bovine adrenal cortex. PC 12 cells also contained predominantly MAO‐A (90%); however, an increased Km for phenylethylamine and a sensitivity of deamination of this MAO‐B substrate to inhibition by clorgyline are indicators of abnormal behavior of MAO in this clonal rat pheochromocytoma cell line.
Distribution of the Glucose‐1,6‐Bisphosphate System in Brain and Retina
Authors: Yip Vera , Pusateri Mary Ellen , Carter Joyce , Rose Irwin A. , Lowry Oliver H. 
Published: October 2006

AbstractThe distribution of glucose‐1,6‐bisphosphate (G16P2) synthase was measured in more than 70 regions of mouse brain, and nine layers of monkey retina. Activities in gray areas varied as much as 10‐fold, in a hierarchical manner, from highest in telencephalon. especially the limbic system, to lowest in cerebellum, medulla, and spinal cord. The synthase levels were significantly correlated among different regions with G16P2 itself, as well as with previously published levels of a brain specific IMP‐dependent G16P2 phosphatase. In contrast, neither G16P2 nor either its synthase or phosphatase correlated positively with phosphoglucomutase. and in all regions the G16P2 levels greatly exceeded requirements for activation of this mutase. This strengthens the view that G16P: has some function besides serving as coenzyme for phosphoglucomutase. However, attempts to correlate the “G16P2 system,” as defined by the three coordinately related elements, synthase, phosphatase, and G16P2, with other enzymes of carbohydrate metabolism, or with regional data of Sokoloff et al. [J. Neurochem. 28, 897–916 (1977)] for glucose consumption, were unsuccessful. This leaves open the possibility that brain G16P2 might serve as a phosphate donor for specific nonmetabolic effector proteins.
Zinc Uptake into Synaptosomes
Authors: Wensink Jan , Molenaar Adriaan J. , Woroniecka Urszula D. , Van den Hamer Cornells J. A. 
Published: October 2006

AbstractZinc uptake‘was studied in synaptosomes, isolated by the Ficoll flotation technique, using the radiotracer 65Zn. True uptake of zinc could be discriminated from binding to the outside of the synaptosomes by the absence of accumulation at 0°C and the dependency of the rate of uptake on the medium osmolarity. The zinc uptake, studied in the presence of various zinc‐complexing agents, showed saturation kinetics when analyzed in terms of [Zn]free, yielding Km= 0.25 μM. The zinc uptake was independent of both ATP and the Na+ gradient. No efflux of zinc could be demonstrated from preloaded synaptosomes due to the formation of insoluble zinc complexes inside the synaptosomes. The results are discussed in terms of the modulation of diverse neurochemical processes by zinc.