glycogen and Ischemic-Attack--Transient

Topics: Acetylcholine; Adenosine Triphosphate; Amines; Amino Acids; Anesthesia, Inhalation; Anesthetics; Animals; Brain; Brain Chemistry; Cyclopropanes; Glucose; Glycogen; Humans; Hypoxia; Ischemic Attack, Transient; Lactates; Nitrous Oxide; Oxygen Consumption; Phosphates; Synaptic Transmission

Loss of cardioprotection by adenosine in hearts stressed by transient ischemia may be due to its effects on glucose metabolism. In the absence of transient ischemia, adenosine inhibits glycolysis, whereas it accelerates glycolysis after transient ischemia. Inasmuch as 5'-AMP-activated protein kinase (AMPK) is implicated as a regulator of glucose and fatty acid utilization, this study determined whether a differential alteration of AMPK activity contributes to acceleration of glycolysis by adenosine in hearts stressed by transient ischemia. Studies were performed in working rat hearts perfused aerobically under normal conditions or after transient ischemia (two 10-min periods of ischemia followed by 5 min of reperfusion). LV work was not affected by adenosine. AMPK phosphorylation was not affected by transient ischemia; however, phosphorylation and activity were increased nine- and threefold, respectively, by adenosine in stressed hearts. Phosphorylation of acetyl-CoA carboxylase and rates of palmitate oxidation were unaltered. Glycolysis and calculated proton production were increased 1.8- and 1.7-fold, respectively, in hearts with elevated AMPK activity. Elevated AMPK activity was associated with inhibition of glycogen synthesis and unchanged rates of glucose uptake and glycogenolysis. Phentolamine, an alpha-adrenoceptor antagonist, which prevents adenosine-induced activation of glycolysis in stressed hearts, prevented AMPK phosphorylation. These data demonstrate that adenosine-induced activation of AMPK after transient ischemia is not sufficient to alter palmitate oxidation or glucose uptake. Rather, activation of AMPK alters partitioning of glucose away from glycogen synthesis; the increase in glycolysis may in part contribute to loss of adenosine-induced cardioprotection in hearts subjected to transient ischemia.

Topics: Acetyl-CoA Carboxylase; Adenine; Adenosine; Adenosine Triphosphate; Adrenergic alpha-Antagonists; AMP-Activated Protein Kinases; Animals; Energy Metabolism; Enzyme Activation; Glucose; Glycogen; Glycolysis; Heart; Ischemic Attack, Transient; Male; Multienzyme Complexes; Myocardium; Palmitates; Phentolamine; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

Insulin has been reported to be neuroprotective during cerebral ischemia/reperfusion. However, it may also increase the sensitivity of cultured cortical neurons to glutamate toxicity. The experiments described here utilized a rat four-vessel occlusion model with cerebral cortical windows to determine the effects of intravenous insulin, alone (I) or combined with glucose (IG) to maintain physiologic blood glucose levels, on the extracellular accumulation of amino acids in superfusates of the cerebral cortex. Aspartate, phosphoethanolamine, taurine and gamma-aminobutyric acid were increased in the I and IG groups and glutamate was increased in the IG group compared to controls during ischemia/reperfusion. Insulin treatment attenuated the rebound in cortical superfusate glucose levels in both groups of animals during reperfusion. The increases in amino acid release during reperfusion may be due to a lack of glycolytically derived energy available for amino acid uptake systems and ionic pumps.

Topics: Animals; Aspartic Acid; Brain Chemistry; Cerebral Cortex; Energy Metabolism; gamma-Aminobutyric Acid; Glucose; Glutamic Acid; Glycogen; Hypoglycemia; Hypoglycemic Agents; Injections, Intravenous; Insulin; Ischemic Attack, Transient; Lactic Acid; Male; Neurotoxins; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Taurine

Cortical metabolites and regional cerebral intracellular pH (pHi) were measured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2 week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest and resuscitation. During total ischemia in AH and CH rats (plasma glucose approximately 30 mM), cortical ATP, PCr, glucose, and glycogen all fell significantly as expected. Lactate levels increased dramatically in association with a concomitant intracellular acidosis. Although lactate reached higher concentrations in AH and CH than NM, pHi was significantly lower only in the AH group. With 5 min of reperfusion, all groups recovered to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group were allowed to recover for 4 days following resuscitation, with outcome being gauged by mortality rate and hippocampal CA1 neuron counts. NM survival rate was significantly better than AH and CH. In particular, no CH rats survived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In summary, our research identified differences in intra-ischemic acid-base status in the two hyperglycemic groups, suggesting that chronic hyperglycemia may alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regarding outcome, and they suggest that factors other than hydrogen ion production during ischemia are responsible for modulating outcome.

Topics: Acidosis, Lactic; Acute Disease; Adenosine Triphosphate; Animals; beta-Galactosidase; Blood Glucose; Cardiopulmonary Resuscitation; Cell Survival; Cerebral Cortex; Chronic Disease; Diabetes Mellitus, Experimental; Energy Metabolism; Glycogen; Heart Arrest; Hippocampus; Hydrogen-Ion Concentration; Hyperglycemia; Image Processing, Computer-Assisted; Ischemic Attack, Transient; Lactase; Male; Neurons; Rats; Rats, Wistar

Hyperglycemia associated with diabetes mellitus will exacerbate neurologic injury after global brain ischemia. Studies in a rat model of forebrain ischemia (bilateral carotid occlusion plus hypotension for 10 min) discovered that acute restoration of normoglycemia in diabetics, using an insulin infusion, resulted in a neurologic outcome that was similar to normoglycemic rats without diabetes. The current study evaluated cerebral glucose, glycogen, lactate, and high-energy phosphate concentrations to identify metabolic correlates that might account for an alteration in postischemic outcome.. Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques.. Before ischemia, D rats had greater concentrations of brain glucose (12.18 +/- 2.67 micromol/g) than did either ID (5.10 +/- 1.33) or ND (3.20 +/- 0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/- 0.28) than in either ID (0.29 +/- 0.09) or ND (0.36 +/- 0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups.. These studies demonstrated greater intraischemic carbohydrate consumption and lactate production in D than in ID or ND rats. Under these conditions, intraischemic-but not postischemic-energy status was better in D rats. Acute insulin therapy in ID rats resulted in a metabolic profile that was similar to that of ND rats. These results suggest that, in this model, primary energy failure during ischemia is not the origin of greater injury in hyperglycemic diabetics, nor is energy enhancement the origin of improved outcome after acute insulin treatment.

Topics: Adenosine Triphosphate; Animals; Brain; Diabetes Mellitus, Experimental; Glucose; Glycogen; Insulin; Ischemic Attack, Transient; Lactates; Lactic Acid; Rats; Rats, Sprague-Dawley; Streptozocin

The primary objective of this study was to attempt to induce excessive intraglial acidosis during ischemia by subjecting rats to an initial insult which leads to post insult accumulation of glycogen, presumed to accumulate primarily in astrocytes. The initial insults were 15 min of transient forebrain ischemia, 30 min of hypoglycemic coma, and intraperitonial injection of methionine-sulphoximine (MSO). In the first two of these insults, glycogen content in neocortex increased to 6-7 mM kg(-1) after 6 h of recovery, and in MSO-treated animals even higher values were measured 24 h after administration ( 12 mM kg(-1)). In spite of this glycogen loading, the amount of lactate formed during a subsequent ischemic insult (of 5-30 min duration) did not exceed values usually obtained during complete ischemia in animals with normal glycogen contents (tissue lactate contents of 15 mM kg(-1)) This was because appreciable amounts of glycogen (3-7 mM kg(-1)) remained undegraded even after 30 min of ischemia. The undigested part largely reflected the extra amount of glycogen accumulated after the initial insults. It is discussed whether this part is unavailable to degradation by phosphorylase.

Topics: Acidosis; Animals; Astrocytes; Brain; Brain Ischemia; Coma; Energy Metabolism; Glycogen; Hypoglycemia; Ischemic Attack, Transient; Male; Methionine Sulfoximine; Phosphorylation; Rats; Rats, Wistar; Reperfusion Injury; Seizures

Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Brain; Creatine; Cyclic N-Oxides; Energy Metabolism; Glucose; Glycogen; Ischemic Attack, Transient; Kinetics; Lactates; Male; Nitrogen Oxides; Phosphocreatine; Rats; Rats, Wistar; Reference Values; Reperfusion; Spin Labels; Time Factors

Localized proton NMR spectroscopy was used to dynamically monitor alterations of cerebral metabolites before, during, and after a 10 min period of global forebrain ischemia in anesthetized rats. Metabolic assessment was based on user-independent determination of absolute brain concentrations at a nominal temporal resolution of 1.6 min. While the concentrations of N-acetyl aspartate (neuronal marker), creatines, cholines, and myo-inositol (glial marker) remained constant, ischemia induced a rapid decline of brain glucose. One hour after reperfusion, glucose recovered to 4.1 +/- 2.2 mmol/kg wet weight significantly above the basal value of 2.3 +/- 1.3 mmol/kg wet weight. Mirroring glucose depletion, lactate increased from 1.0 +/- 0.6 to 13.5 +/- 1.5 mmol/kg wet weight 10-15 min after the onset of ischemia. During reperfusion lactate clearance was characterized by a first-order rate constant of 0.03/min. The time courses of glucose and lactate reflect the rapid onset of anaerobic glycolysis during states of critically diminished blood flow. Assuming complete ischemia the production of lactate from glucose and cerebral glycogen stores yields a brain glycogen concentration of 4.7 +/- 0.9 mmol glycosyl unit/kg wet weight. Elevation of brain glucose during early reperfusion suggests a transient mismatch of glucose uptake and consumption during the first 1-2 hours post ischemia.

Topics: Animals; Aspartic Acid; Brain; Choline; Creatine; Glucose; Glycogen; Inositol; Ischemic Attack, Transient; Kinetics; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Rats; Rats, Wistar; Reperfusion

The present study was undertaken to explore how transient ischemia in rats alters cerebral metabolic capacity and how postischemic metabolism and blood flow are coupled during intense activation. After 6 h of recovery following transient forebrain ischemia 15 min in duration, bicuculline seizures were induced, and brains were frozen in situ after 0.5 or 5 min of seizure discharge. At these times, levels of labile tissue metabolites were measured, whereas the cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) were measured after 5 min of seizure activity. After 6 h of recovery, and before seizures, animals had a 40-50% reduction in CMRO2 and CBF. However, because CMRO2 rose three-fold and CBF fivefold during seizures, CMRO2 and CBF during seizures were similar in control and postischemic rats. Changes in labile metabolites due to the preceding ischemia encompassed an increased phosphocreatine/creatine ratio, as well as raised glucose and glycogen concentrations. Seizures gave rise to minimal metabolic perturbation, essentially comprising reduced glucose and glycogen contents and raised lactate concentrations. It is concluded that although transient ischemia leads to metabolic depression and a fall in CBF, the metabolic capacity of the tissue is retained, and drug-induced seizures lead to a coupled rise in metabolic rate and blood flow.

Topics: Animals; Bicuculline; Cerebrovascular Circulation; Creatine; Energy Metabolism; Glucose; Glycogen; Ischemic Attack, Transient; Kinetics; Male; Oxygen; Phosphocreatine; Prosencephalon; Rats; Rats, Wistar; Seizures

Brain glycogen stores are localized primarily to glia and undergo continuous utilization and resynthesis. To study the function of glycogen under normal conditions in brain, we developed an autoradiographic method of demonstrating local-glycogen utilization in the awake rat. The method employs labeling of brain glycogen with 14C(3,4)glucose, in situ microwave fixation of brain metabolism, and anhydrous tissue preparation. With this technique, tactile stimulation of the rat face and vibrissae was found to accelerate the utilization of labeled glycogen in brain regions known to receive sensory input from face and vibrissae: the contralateral somatosensory cortex and the ipsilateral trigeminal, sensory and motor nuclei. These findings demonstrate a link between neuronal activity and local glycogen utilization in mammalian brain and suggest that, like other tissues, brain may respond to sudden increases in energy demand in part by rapid glycolytic metabolism of glycogen. As cerebral glycogen is restricted primarily to glia, these observations also support a close coupling of glial energy metabolism with neuronal activity.

Topics: Animals; Autoradiography; Brain; Carbon Radioisotopes; Glucose; Glycogen; Ischemic Attack, Transient; Kinetics; Male; Microwaves; Organ Specificity; Rats; Rats, Sprague-Dawley; Time Factors

Hyperglycemia aggravates brain pathologic outcome following middle cerebral artery (MCA) occlusion in cats. We presently determined if hyperglycemia during occlusion leads to high lactic acid accumulations in the ischemic MCA territory. We measured brain metabolite concentrations in 14 MCA territory sites at 0.5 and 4 h following occlusion in hyper- (20 mM) and normoglycemic (5 mM) cats and correlated these results with previous brain pathologic findings. Hyper- versus normoglycemia during MCA occlusion resulted in significantly higher lactate concentrations in the ischemic territory and more numerous loci with lactates greater than 17 mumol/g. At 0.5 h of occlusion, ATP levels were lower in normoglycemic cats, while at 4 h, ATP was similarly reduced (40%) in both glycemia groups. At 4 h, PCr was more reduced in hyperglycemics secondary to a greater brain tissue acidosis. Carbohydrate substrates at 0.5 h were more markedly depleted in normoglycemics, likely limiting lactate accumulation (34.3% versus only 5.0% of sites in hyperglycemics with glucose less than 0.5 mumol/g). Although lactate was markedly elevated at both 0.5 and 4 h in hyperglycemic ischemic territories, clip release at 4 versus 0.5 h yields a significantly poorer brain pathologic outcome. Correspondingly, intracellular pH, calculated from the creatine kinase equilibrium, was more markedly depressed at 4 than at 0.5 h of occlusion, demonstrating a time-dependent dissociation between tissue lactate and hydrogen ion accumulations. The present findings show that following MCA occlusion (a) hyperglycemia increases the magnitude and topographic extent of marked tissue lactic acidosis, (b) infarct size following 0.5 h of clip release correlates more closely with tissue acidosis than with lactate concentrations, (c) ischemic tissue ATP concentrations correlate poorly with infarct size, (d) normoglycemia limits lactate accumulation during focal ischemia because tissue glucose is depleted, and (e) early during ischemia, tissue buffering or antiport mechanisms may prevent marked increases in intracellular hydrogen ion activity.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Glucose; Brain; Cats; Cerebral Arteries; Cerebrovascular Circulation; Creatine; Female; Glucose; Glycogen; Hydrogen-Ion Concentration; Ischemic Attack, Transient; Lactates; Lactic Acid; Male; Phosphocreatine

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Monophosphate; Animals; Azepines; Brain; Creatine; Dimethyl Sulfoxide; Dogs; Electroencephalography; Evoked Potentials, Auditory; Free Radical Scavengers; Glucose; Glycogen; Hydrogen-Ion Concentration; Ischemic Attack, Transient; Kinetics; Oxygen; Phosphocreatine; Platelet Activating Factor; Thienopyridines; Triazoles; Vascular Resistance

Microwave fixation in situ was used to assess regional glycogen and glucose stores in normal rat brain. Glycogen levels were highest in the cerebellum and pons/medulla (38.0 and 35.6 nmol/mg protein), and lowest in the striatum and cerebral cortex (17.4 and 23.6 nmol/mg protein respectively). Glucose concentrations paralleled glycogen, ranging from 5.9 to 10.8 nmol/mg protein. Glycogen, glucose, and lactate were measured during complete global ischaemia (decapitation) to assess regional differences in ischaemic metabolism. Those regions which in normal brain contain higher glycogen and glucose stores were found to maintain significantly higher levels of glycogen and glucose for at least 2 minutes of ischaemia. Lactate accumulated to highest levels after 30 minutes of ischaemia in those regions with highest glucose and glycogen stores. Lactate levels did not, however, rise above 90 nmol/mg protein in any brain region, a level well below that considered potentially neurotoxic. The data indicate considerable regional differences in normal and ischaemic glycogen metabolism that might contribute to known regional differences in vulnerability to global ischaemia.

Topics: Animals; Energy Metabolism; Glucose; Glycogen; Ischemic Attack, Transient; Lactates; Lactic Acid; Male; Rats; Rats, Inbred Strains; Time Factors

The contributions of five variables believed to influence the brain's metabolism of O2 during hypoxia [duration, PaO2, delta CMRO2 (the difference between normal and experimental oxygen uptake), O2 availability (blood O2 content.CBF), and O2 deficit (delta CMRO2.duration)] were assessed by stepwise and multiple linear regression. Levels of brain tissue carbohydrates (lactate, glucose, and glycogen) and energy metabolites [ATP, AMP, and creatine phosphate (CrP)] were significantly influenced by O2 deficit during hypoxia, as was final CMRO2. After 60 min of reoxygenation, levels of tissue lactate, glucose, ATP, and AMP were related statistically to the O2 deficit during hypoxia; however, CMRO2 changes were always associated more significantly with O2 availability during hypoxia. Creatine (Cr) and CrP levels in the brain following reoxygenation were correlated more to delta CMRO2 during hypoxia. Changes in some brain carbohydrate (lactate and glucose), energy metabolite (ATP and AMP) levels, and [H+]i induced by complete ischemia were also influenced by O2 deficit. After 60 min of postischemic reoxygenation, brain carbohydrate (lactate, glucose, and glycogen) and energy metabolite (ATP, AMP, CrP, and Cr) correlated with O2 deficit during ischemia. We conclude that "O2 deficit" is an excellent gauge of insult intensity which is related to observed changes in nearly two-thirds of the brain metabolites we studied during and following hypoxia and ischemia.

Topics: Adenine Nucleotides; Animals; Brain; Cerebrovascular Circulation; Creatine; Dogs; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Ischemic Attack, Transient; Lactates; Lactic Acid; Oxygen; Oxygen Consumption; Phosphocreatine; Regression Analysis

The time course of the reduction in brain protein synthesis following transient bilateral ischemia in the gerbil was characterized and compared with changes in a number of metabolites related to brain energy metabolism. The recovery of brain protein synthesis was similar following ischemic periods of 5, 10, or 20 min; in vitro incorporation activity of brain supernatants was reduced to approximately 10% of control at 10 or 30 min recirculation, showed slight recovery at 60 min, and returned to 60% of control activity by 4 h. Protein synthesis activity was indistinguishable from control at 24 h. One minute of ischemia produced no detectable effect on protein synthesis measured after 30 min reperfusion; longer periods of ischemia resulted in progressive inhibition, with 5 min producing the maximal effect. Pentobarbital (50 mg/kg) increased by 1-2 min the threshold ischemic duration required to produce a given effect. Whereas most metabolites recovered quickly following 5 min ischemia, glycogen showed a delayed recovery comparable to that seen for protein synthesis. These results are discussed in relation to possible mechanisms for the coordinate regulation of brain energy metabolism and protein synthesis. An improved method for the fluorimetric measurement of guanine nucleotides is described.

Topics: Adenine Nucleotides; Animals; Brain; Energy Metabolism; Gerbillinae; Glycogen; Guanine Nucleotides; Ischemic Attack, Transient; Kinetics; Lactates; Lactic Acid; Male; NADP; Nerve Tissue Proteins; Pentobarbital; Phosphocreatine; Pyruvates; Pyruvic Acid

Treatment of gerbils with 40 mg/kg of pentobarbital (i.p.) reduced the metabolic rate in the hippocampus and cerebral cortex by approximately 60%. However, the depression of metabolic rate was lost within 40 s of ischemia and further, pentobarbital delayed but did not prevent the depletion of energy metabolites observed in the ischemic brain.

Topics: Adenosine Triphosphate; Animals; Brain; Energy Metabolism; Gerbillinae; Glucose; Glycogen; Ischemic Attack, Transient; Kinetics; Male; Pentobarbital; Phosphocreatine

This study documents the Na+,K+-ATPase activity as well as selected parameters of oxidative metabolism and electrophysiological function in rat brain exposed to ischemia produced by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. During a 0.5-h ischemic exposure in which the electroencephalograph (EEG) was abolished and energy metabolism severly compromised the Na+,K+-ATPase showed a capability for enhanced activity (120-140% of control). On recirculation, the Na+,K+-ATPase activity showed a phasic pattern, which was characterized by normal values at 0.25-2 h, increased values (115-125% of control) at 3-24 h, and, finally, normal values at 72 h of recirculation, respectively. The maintenance of Na+,K+-ATPase integrity was correlated with a gradual return of EEG activity and virtually complete restitution of the cerebral energy state during the 72 h of recirculation. Measurements of thiobarbituric acid reactive material and water soluble antioxidant during ischemia and recirculation gave no evidence of the presence of significant free radical lipid peroxidation in this model. It is concluded that Na+,K+-ATPase and its associated membrane lipids are not irreversibly damaged by ischemia in which the tissue lactacidosis is limited to less than 20 mumol g-1.

Topics: Adenine Nucleotides; Animals; Brain; Brain Chemistry; Electroencephalography; Glucose; Glycogen; Ischemic Attack, Transient; Lactates; Lactic Acid; Lipid Peroxides; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase

In order to study if rapid elevation of blood pressure is associated with cerebral ischemia, anesthetized (70% N2O) and artificially ventilated rats were subjected to angiotensin-induced hypertension. After a 5 min hypertensive period, cerebral cortex tissue was frozen in situ for subsequent measurements of labile glycolytic metabolites, ammonia, and organic phosphates. The degree of hypertension induced, which gave evidence of blood-brain barrier damage in 7 of 8 rats, did not affect the tissue concentrations of labile metabolites. It is concluded that ischemia does not contribute to the barrier damage, nor is it likely to be the cause of the clinical symptoms that may occur in conscious rats in the same experimental model.

Topics: Acute Disease; Ammonia; Angiotensin II; Animals; Blood-Brain Barrier; Brain; Energy Metabolism; Glucose; Glycogen; Hypertension; Ischemic Attack, Transient; Male; Organophosphorus Compounds; Rats; Rats, Inbred Strains

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Brain; Cerebral Hemorrhage; Cerebrovascular Disorders; Electron Transport Complex IV; Female; Glycogen; Histocytochemistry; Humans; Ischemia; Ischemic Attack, Transient; Leukocytes; Male; Middle Aged; Peroxidases

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Aspartic Acid; Dextrans; Electron Transport Complex IV; Female; Glycogen; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Leukocytes; Male; Middle Aged; Peroxidases; Potassium Magnesium Aspartate

Topics: Animals; Brain; Carotid Arteries; Glucosyltransferases; Glycogen; Hypoxia, Brain; Ischemic Attack, Transient; Ligation; Male; Oxygen Consumption; Rats

Topics: Acute Disease; Adenine Nucleotides; Adenosine Triphosphate; Alanine Transaminase; Animals; Aspartate Aminotransferases; Cerebellum; Citrates; Fructosephosphates; Gluconates; Glucose; Glucosephosphates; Glycogen; Hypoxia, Brain; Ischemic Attack, Transient; Ketoglutaric Acids; Lactates; Malates; Male; Medulla Oblongata; Mesencephalon; Mice; Oxygen Consumption; Parietal Lobe; Phosphocreatine; Pons; Pyruvates; Respiratory Insufficiency

Topics: Anesthesia, General; Animals; Brain; Carotid Arteries; Cytoplasm; Female; Glycogen; Ischemic Attack, Transient; Ligation; Male; Microscopy, Electron; Nerve Tissue; Neuroglia; Polysaccharides; Rats; Time Factors

Topics: Acid Phosphatase; Animals; Brain; Cerebral Cortex; Cerebrovascular Disorders; Disease Models, Animal; Glucuronidase; Glycogen; Hemiplegia; Hydrolases; Hypoxia; Hypoxia, Brain; Ischemic Attack, Transient; Lysosomes; Male; Mitochondria; Rats

Topics: Adenosine Triphosphate; Anesthesia; Animals; Centrifugation; Cerebral Cortex; Disease Models, Animal; Fluorometry; Glucose; Glycogen; Ischemic Attack, Transient; Lipid Metabolism; Male; Mice; Phosphates; Phosphocreatine

Topics: Animals; Electron Transport Complex IV; Glycogen; Hydrolases; Ischemic Attack, Transient; Lysosomes; Nerve Tissue Proteins; Rats; Water

Topics: Adenosine Triphosphate; Adult; Aged; Animals; Astrocytoma; Brain; Brain Neoplasms; Cerebral Cortex; Craniopharyngioma; Fluorometry; Frontal Lobe; Glucose; Glycogen; Glycolysis; Humans; In Vitro Techniques; Ischemic Attack, Transient; Mice; Middle Aged; Oxygen Consumption; Parietal Lobe; Phosphocreatine; Spectrophotometry

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Fluorometry; Glioma; Glucose; Glycogen; Ischemic Attack, Transient; Lactates; Methylcholanthrene; Mice; Neoplasms, Experimental; Phosphocreatine