phosphocreatine and Cerebral-Hemorrhage

31P-NMR spectroscopic studies were performed in vivo on brains of rats chronically infused for 7 and 14 days with 30% ethanol (in the third cerebral ventricle). Peripheral blood alcohol concentration (BAC) rose to between 16.5-30.5 mg/dl. Brain intracellular free Mg2+ ([Mg2+]i) fell 33-39%, brain mitochondrial cytosolic phosphorylation potential (CPP) fell 31-48%, and brain phosphocreatine (PCr) fell approximately 15%; however, neither brain intracellular free hydrogen ion concentration (pHi) nor brain intracellular inorganic phosphate (Pi) were affected significantly by the chronic release of ethanol from the brain implants. Correlations were found between [Mg2+]i and [PCr] and between [Mg2+]i and CPP. Although brain free [MgADP] was not affected, [MgATP] fell by almost 20% accompanied by a 35-40% rise in free [ADP]. Interestingly, 14-day surgical implantation of 0.9% sterile saline into the third cerebral ventricle was associated with a 20% fall in brain [Mg2+]i and a 35% fall in CPP; however, PCr, ATP, or pHi was not significantly altered. Systemic administration of 4 g/kg ethanol into the 7- and 14-day chronic ethanol animals resulted in a 9- and 12-fold increase in hemorrhagic stroke mortality compared to naive, control rats. Eating habits, grooming, gait and arterial blood pressure were not affected by the chronic brain implantation of ethanol. These data lend support to the notion, primarily based on epidemiologic evidence, that chronic exposure to alcohol can pose a high risk for hemorrhagic stroke. Our alcohol pump-implanted rats also might provide a new model of slow, moderate alcohol intoxication.

Topics: Adenosine Triphosphate; Animals; Brain; Cerebral Hemorrhage; Cerebrovascular Disorders; Cytosol; Energy Metabolism; Ethanol; Hydrogen-Ion Concentration; Infusion Pumps; Magnesium; Magnetic Resonance Spectroscopy; Male; Mitochondria; Phosphocreatine; Phosphorylation; Rats; Rats, Wistar

The authors previously demonstrated, in a large-animal intracerebral hemorrhage (ICH) model, that markedly edematous ("translucent") white matter regions (> 10% increases in water contents) containing high levels of clot-derived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the concentrations of high-energy phosphate, carbohydrate substrate, and lactate in these and other perihematomal white and gray matter regions during the early hours following experimental ICH.. The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a physiologically controlled model in pigs (weighing approximately 7 kg each) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water contents were then measured in white and gray matter located ipsi- and contralateral to the hematomas, and metabolite concentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentrations increased two- to fivefold compared with control during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5 hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 micromol/g) at all times. In gyral gray matter overlying the hematoma, water contents and glycogen levels were significantly increased at 5 and 8 hours, whereas lactate levels were increased two- to fourfold at all times.. These results, which demonstrate normal to increased high-energy phosphate and carbohydrate substrate concentrations in edematous perihematomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present, lactate accumulation in edematous white matter is not caused by stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the blood entering the brain's extracellular space during ICH are several-fold higher than normal levels, the authors speculate, on the basis of work reported by Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced aerobic glycolysis and lactate is generated at a rate that exceeds utilization.

Topics: Adenosine Triphosphate; Aerobiosis; Animals; Astrocytes; Blood Proteins; Body Water; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Disease Models, Animal; Energy Metabolism; Extracellular Space; Frontal Lobe; Glucose; Glutamates; Glycogen; Glycolysis; Hematoma; Lactates; Phosphocreatine; Swine; Time Factors

This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion.. Prospective, controlled laboratory investigation.. One hundred six pentobarbital-anesthetized cats.. The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion.. Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage.. Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Brain Ischemia; Cats; Cerebral Arteries; Cerebral Hemorrhage; Cerebral Infarction; Constriction; Glucose; Hyperglycemia; Lactates; Lactic Acid; Linear Models; Phosphocreatine; Prospective Studies; Risk Factors

The purpose of this study was to determine whether cerebral metabolic changes occur after intraventricular hemorrhage in the newborn. Five babies with bilateral grade 3 to 4 intraventricular hemorrhage were compared with 15 preterm infants without intraventricular hemorrhage. Cerebral high-energy phosphorus metabolites and intracellular pH were measured with in vivo 31P nuclear magnetic resonance spectroscopy. Spectra were collected initially within the first 2 weeks of life, and then every other week until discharged from the hospital. The phosphocreatine to inorganic phosphate ratio and the phosphocreatine to adenosine triphosphate ratio were significantly lower in the group with intraventricular hemorrhage, but differences in intracellular pH were not significant. Differences between babies with and without intraventricular hemorrhage varied with postconceptional age: in those with intraventricular hemorrhage, the phosphocreatine to adenosine triphosphate ratio was decreased at all postconceptional ages, and the phosphocreatine to inorganic phosphate ratio was lower in babies with intraventricular hemorrhage and younger than 30 weeks. Results of this study confirm the presence of chronic metabolic changes following intraventricular hemorrhage which may exacerbate neurologic damage after intraventricular hemorrhage in the newborn.

Topics: Adenosine Triphosphate; Cerebral Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus Isotopes

Intracellular energy metabolism was studied by phosphorus magnetic resonance spectroscopy in the brains of 27 preterm and term infants with increased echodensities consistent with hypoxic-ischaemic injury and 18 comparable normal infants. In the normal infants the phosphocreatine (PCr)/inorganic orthophosphate (Pi) ratio increased significantly from 0.77 +/- 0.24 (95% confidence limits) at a gestational plus postnatal age of 28 weeks to 1.09 +/- 0.24 at 42 weeks. 9 of the 15 infants with increased echodensities whose PCr/Pi ratios fell below the normal range died; in all 6 survivors cerebral atrophy developed (cysts in brain tissue or microcephaly). In contrast, all 12 infants with increased echodensities whose PCr/Pi ratios remained within the normal range survived, although cerebral atrophy developed in 3 with ratios towards the lower limit of normal.

Topics: Age Factors; Brain; Brain Ischemia; Cerebral Hemorrhage; Energy Metabolism; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature, Diseases; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Ultrasonography