phosphocreatine and Brain-Edema

Topics: Adaptation, Biological; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Amino Acids; Animals; Brain; Brain Edema; Energy Metabolism; Glucose; Inulin; Lactates; Muscles; Osmolar Concentration; Osmotic Pressure; Phosphocreatine; Potassium; Rats; Sodium; Sucrose; Time Factors; Water Intoxication

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Brain; Brain Edema; Humans; Hypercapnia; Hypoxia, Brain; Ischemic Attack, Transient; Lactates; Phosphocreatine; Pyruvates

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Brain; Brain Chemistry; Brain Damage, Chronic; Brain Edema; Carbon Dioxide; Cats; Cerebrovascular Circulation; Cerebrovascular Disorders; Electroencephalography; Heart Arrest; Humans; Hypotension; Hypoxia; Hypoxia, Brain; Indicator Dilution Techniques; Ischemia; Lactates; Mathematics; Oxygen; Phosphocreatine; Prognosis; Vasomotor System

Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.

Topics: Adenosine Triphosphate; Animals; Aspartic Acid; Brain Edema; Cerebrum; Diabetes Mellitus, Experimental; Diabetic Ketoacidosis; Diet, High-Fat; Hyperglycemia; Lactic Acid; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Rats; Water

Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking.. We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 x 2 factorial study design.. Cerebral intracellular pH was decreased during DKA compared with control (mean +/- SE difference -0.13 +/- 0.03; P < 0.001), and lactate/Cr was elevated (0.09 +/- 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (-0.32 +/- 0.10, P = 0.003, and -0.14 +/- 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment.. These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment--consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline.

Topics: Animals; Aspartic Acid; Brain; Brain Edema; Bumetanide; Cerebrovascular Circulation; Creatinine; Diabetic Ketoacidosis; Diuretics; Fluid Therapy; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Lactic Acid; Magnetic Resonance Spectroscopy; Phosphocreatine; Rats; Rats, Sprague-Dawley; Sodium Chloride

Near-infrared spectroscopy (NIRS) offers the ability to assess brain function at the bedside of critically ill neonates. Our group previously demonstrated a persistent reduction in the cerebral metabolic rate of oxygen (CMRO(2)) after hypoxia-ischemia (HI) in newborn piglets. The purpose of this current study was to determine the causes of this reduction by combining NIRS with magnetic resonance spectroscopy (MRS) to measure high-energy metabolites and diffusion-weighted imaging to measure cellular edema. Nine piglets were exposed to 30 min of HI and nine piglets served as controls. Proton and phosphorous MRS spectra, apparent diffusion coefficient (ADC) maps, and CMRO(2) measurements were collected periodically before and for 5.5 h after HI. A significant decrease in CMRO(2) (26 +/- 7%) was observed after HI. Incomplete recovery of nucleotide triphosphate concentration (8 +/- 3%

Topics: Animals; Animals, Newborn; Brain; Brain Edema; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Energy Metabolism; Hypoxia-Ischemia, Brain; Lactic Acid; Magnetic Resonance Spectroscopy; Mitochondria; Oxygen Consumption; Phosphates; Phosphocreatine; Recovery of Function; Spectroscopy, Near-Infrared; Swine; Time Factors

A decrease in the intracellular levels of osmotically active species has invariably been seen after swelling of mammalian brain tissue preparations. The exact identity of the species, and the manner of their decrease, remain to be described. We investigated the swelling-activated decrease of organic osmolytes in rat cortical brain slices using (1)H- and (31)P-magnetic resonance spectroscopy. We found that acute hypo-osmotic shock causes decreases in the levels of a range of intracellular amino acids and amino acid derivatives, N-acetyl-aspartate, creatine, GABA, glutamate, hypotaurine, and also in the levels of the methylamines glycerol-phosphorylcholine, phosphorylcholine and choline. Incubation of cortical slices with the anion channel blockers niflumic acid and tamoxifen caused inhibition of organic osmolyte efflux, suggesting that such osmolyte efflux occurs through anion channels. Intracellular phosphocreatine was also seen to decrease during acute hypo-osmotic superfusion, although intracellular ATP remained constant. In addition, the acidification of an intracellular compartment was observed during hypo-osmotic superfusion. Our results suggest a link between brain energy reserve and brain osmoregulation.

Topics: Adenosine Triphosphate; Animals; Anions; Antineoplastic Agents, Hormonal; Brain Edema; Cerebral Cortex; Cyclooxygenase Inhibitors; Female; Hypotonic Solutions; Ion Channels; Isotonic Solutions; Magnetic Resonance Spectroscopy; Niflumic Acid; Organ Culture Techniques; Osmotic Pressure; Phosphocreatine; Phosphorus Isotopes; Protons; Rats; Rats, Wistar; Tamoxifen

The effect of induced hypertension treatment on cerebral ischemia is still controversial. We investigated the preferred blood pressure manipulation level and pressor agent required to reduce cerebral ischemic injury following transient forebrain ischemia induced by bilateral occlusion of the common carotid arteries in anesthetized gerbils. Following 60-min cerebral ischemia, we evaluated the preferred blood pressure manipulation level and pressor agent required to treat cerebral ischemic injury after reperfusion by examining the effects of different levels of mean arterial blood pressure (MABP), increased with phenylephrine or angiotensin II or decreased by blood withdrawal, on cerebral blood flow (CBF), survival ratio, cerebral edema, and brain energy metabolism following transient forebrain ischemia in gerbils. Mild phenylephrine-induced hypertension treatment (21+/-4 mmHg) during post-cerebral ischemia-reperfusion improved the survival ratio and reduced cerebral edema, which was also associated with an increase in local CBF and a recovery of brain energy metabolism. However, intense phenylephrine-induced hypertension, angiotensin II-induced hypertension, or hypotension worsen the survival rate and produced extra cerebral edema, that were also associated with deterioration of brain energy metabolism. These results demonstrate that a mild induced hypertension with phenylephrine (21+/-4 mmHg above the baseline level) results in reduction of the cerebral edema and improves the survival ratio and brain energy metabolism. Furthermore, angiotensin II may have neurotoxic effect to use as the pressor agent for induced hypertension after cerebral ischemia.

Topics: Adenosine Triphosphate; Analysis of Variance; Angiotensin II; Animals; Blood Pressure; Brain Edema; Cerebrovascular Circulation; Energy Metabolism; Gerbillinae; Hypertension; Ischemic Attack, Transient; Male; Phenylephrine; Phosphocreatine; Prosencephalon; Reperfusion Injury; Survival Rate

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

Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1) (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(-1). In seven of the animals, a "secondary" failure of energy metabolism then evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1) at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADCglobal correlated linearly with the concentration ratio [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear relationship was demonstrated between ADCglobal and the concentration ratio [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Blood-Brain Barrier; Body Water; Brain; Brain Damage, Chronic; Brain Edema; Diffusion; Humans; Hypoxia, Brain; Image Processing, Computer-Assisted; Infant, Newborn; Magnetic Resonance Spectroscopy; Phantoms, Imaging; Phosphates; Phosphocreatine; Swine

T2 and diffusion weighted MRI, as well as 31P and 1H MRS were performed in kaolin-induced hydrocephalic rats. Extracellular white matter edema was detected in the early stages of progressive hydrocephalus. Phosphocreatine (PCr)/inorganic phosphate (Pi) ratios in hydrocephalic animals were decreased compared to controls, and lactate was detected during the acute and chronic stages of hydrocephalus. These MR spectroscopic results are indicative of a compromised energy metabolism and suggest the occurrence of cerebral ischemia in experimental hydrocephalus.

Topics: Animals; Brain; Brain Edema; Brain Ischemia; Energy Metabolism; Hydrocephalus; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Rats; Rats, Wistar

The metabolism of the brain was investigated in eight patients with peritumoral edema, six patients with ischemic stroke, and 28 normal controls using proton magnetic resonance (MR) spectroscopy. The MR studies were performed using a 1.5-T whole-body imaging and spectroscopy system with a 1500-msec repetition time (TR) and a 270-msec echo time (TE). The peak areas for N-acetyl-aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and lactate (Lac) were measured, and the NAA/Cr, Cho/Cr, and Lac/Cr ratios were calculated. To quantify and compare the serial spectra, relaxation effects were investigated by acquisitions at two different points (TRs or TEs) and by monoexponential fitting. The normal NAA/Cr and Cho/Cr ratios were 2.76 and 1.09, respectively. Lac could not be identified in normal brains. In ischemic stroke and peritumoral edema, significantly increased Lac/Cr and decreased NAA/Cr ratios were observed. Resolution of peritumoral edema was associated with normalized NAA/Cr ratio and disappearance of Lac. The T1 relaxation times of the metabolites were similar in normal brain and peritumoral edema, but the T2 values were significantly shortened. Serial measurements of T2 values in two patients with peritumoral edema showed gradual normalization corresponding to improvement of the edema. To absolutely quantify metabolite concentrations in edema, changes in relaxation times should be considered.

Topics: Adult; Aspartic Acid; Brain; Brain Edema; Cerebrovascular Disorders; Creatinine; Female; Humans; Lactates; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine

Atrial natriuretic peptide (ANP) regulates fluid and electrolyte homeostasis in the central nervous system. In this study, we evaluated the effects of ANP on brain edema, intracranial pressure (ICP) and cerebral energy metabolism in congenital hydrocephalus in rats. Brain edema, indicated by the longitudinal relaxation time (T1), was evaluated by 1H-magnetic resonance imaging (MRI). The ICP was monitored with a miniature pressure-transducer with telemetric system. Cerebral energy metabolism, indicated by PCr/Pi ratio, was measured by 31P-magnetic resonance spectroscopy (MRS). The rats were given 10 microliters of ANP in the left cerebral ventricle. Three different concentrations of ANP were given; 0.2 (group I), 2.0 (group II) and 20.0 (group III) micrograms/10 microliters, respectively. 10 microliters of saline was injected into the ventricle of the control group rats. There were no significant changes of ICP, T1 value and PCr/Pi ratio among the control group, group I and group II. In group III, in contrast, ICP decreased significantly at 20 minutes after ANP administration and stayed at this ICP level for 60 minutes. The T1 value decreased and PCr/Pi ratio increased 30 minutes after ANP administration. This study revealed that intraventricularly administered ANP could decrease ICP, reduce brain edema and improve the cerebral energy metabolism in rats with congenital hydrocephalus.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Brain; Brain Edema; Cerebral Ventricles; Energy Metabolism; Hydrocephalus; Intracranial Pressure; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Water-Electrolyte Balance

F98 gliomas, E367 neuroblastomas, and RN6 Schwannomas in rat brain were studied non-invasively in vivo by localized proton MR spectroscopy (MRS). The spectra obtained from homotopic brain contralateral to the tumors were qualitatively indistinguishable from those of normal rat brain in vivo and showed resonance lines assigned to N-acetylaspartate, glutamate, total creatine (creatine and phosphocreatine), choline, glucose, and myo-inositol. The tumor spectra displayed marked differences compared to those obtained from contralateral brain. There were increases in choline, myo-inositol and lipids, which are presumably associated with increased membrane turnover. The presence of lactate indicated anaerobic glycolysis. Other differences included the absence of signals from NAA resulting from the destruction or displacement of neuronal tissue by the tumor. There was also a loss of total creatine. Although the spectra of all three tumor types were distinct from contralateral brain, there were no obvious differences between the different tumor types.

Topics: Animals; Aspartic Acid; Blood Glucose; Brain Edema; Brain Neoplasms; Caudate Nucleus; Cell Line; Choline; Creatinine; Energy Metabolism; Glioma; Glutamic Acid; Inositol; Magnetic Resonance Imaging; Male; Neoplasm Transplantation; Neurilemmoma; Neuroblastoma; Phosphocreatine; Rats; Rats, Inbred F344

The aim of the present study was to determine the effects of a hyperosmotic agent, 10% glycerol, on both brain energy metabolism and intracellular pH (pHi) in experimental vasogenic brain edema. Vasogenic brain edema was induced by cold injury applied to bilateral parietal portions in 13 mongrel dogs (7 glycerol, 6 control) while, 3 dogs were used as control. Before and at 24 hours after the injury, sequential phosphorous-31 magnetic resonance spectroscopy (31P-MRS) was performed for 2 hours in order to determine phosphocreatine (PCr), beta-adenosine triphosphate (beta-ATP), inorganic phosphate (Pi) levels and pHi. At 24 hours following cold injury, both PCr/Pi and ATP/Pi ratios significantly decreased from 7.75 to 3.97 and from 2.26 to 1.25, respectively. Furthermore, a moderate decrease in pHi of 7.16 to 7.01 was significantly demonstrated during the same experimental period. Administration of glycerol for 30 minutes significantly increased PCr/Pi from 3.97 to 5.06 and ATP/Pi from 1.25 to 1.72, respectively. Also, glycerol administration caused a significant increase in pHi from 7.01 to 7.11. This study indicates that cryogenic injury, in which formation and expansion of vasogenic brain edema a known to occur, results in disturbed brain energy metabolism and in intracellular acidosis; moreover, the administration of glycerol can ameliorate either or both of these derangements.

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Animals; Brain Edema; Brain Injuries; Dogs; Energy Metabolism; Freezing; Glycerol; Intracellular Fluid; Magnetic Resonance Spectroscopy; Parietal Lobe; Phosphates; Phosphocreatine; Water-Electrolyte Balance

Postischemic evoked potential recovery correlates with acidosis during ischemia and early reperfusion. Acidosis promotes lipid peroxidation in vitro. We tested the hypothesis that the 21-aminosteroid tirilazad mesylate (U74006F), an inhibitor of lipid peroxidation in vitro, ameliorates somatosensory evoked potential recovery and acidosis during reperfusion after severe incomplete cerebral ischemia.. Cerebral perfusion pressure was reduced to 11 +/- 1 mm Hg (+/- SEM) for 30 minutes by cerebral ventricular fluid infusion in anesthetized dogs. Cerebral intracellular pH and high-energy phosphates were measured by magnetic resonance spectroscopy. Dogs were randomized to receive vehicle (citrate buffer; n = 8) or tirilazad (1 mg/kg; n = 8) before ischemia in a blinded study.. Cerebral blood flow was reduced to 6 +/- 1 mL/min per 100 g during ischemia, resulting in nearly complete loss of high-energy phosphates and an intracellular pH of 6.0-6.1 in both groups. Initial postischemic hyperemia was similar between groups but lasted longer in the vehicle group. Tirilazad accelerated mean recovery time of intracellular pH from 31 +/- 5 to 15 +/- 3 minutes and of inorganic phosphate from 13 +/- 2 to 6 +/- 1 minutes. Recovery of somatosensory evoked potential amplitude was greater with tirilazad (49 +/- 3%) than vehicle (33 +/- 6%). Fractional cortical water content was less with tirilazad (0.819 +/- 0.003) than vehicle (0.831 +/- 0.002).. Tirilazad attenuates cerebral edema and improves somatosensory evoked potential recovery after incomplete ischemia associated with severe acidosis. Accelerated pH and inorganic phosphate recovery indicates that this antioxidant acts during the early minutes of reperfusion.

Topics: Acidosis; Adenosine Triphosphate; Animals; Bicarbonates; Brain; Brain Edema; Brain Ischemia; Cytoplasm; Dogs; Drug Evaluation, Preclinical; Evoked Potentials, Somatosensory; Hydrogen-Ion Concentration; Male; Phosphocreatine; Pregnatrienes; Reactive Oxygen Species; Reperfusion Injury

A new approach to the study of glucose phosphorylation in brain slices is described. It is based on timed incubation with nonradioactive 2-deoxyglucose (DG), after which the tissue levels of DG and 2-deoxyglucose-6-phosphate (DG6P) are measured separately with sensitive enzymatic methods applied to specific small subregions. The smallest samples had dry weights of approximately 0.5 microgram. Direct measurements in different regions of hippocampal slices showed that within 6 min after exposure to DG, the ratios of DG to glucose in the tissue were almost the same as in the incubation medium, which simplifies the calculation of glucose phosphorylation rates and increases their reliability. Data are given for ATP, phosphocreatine, sucrose space, and K+ in specific subregions of the slices. DG6P accumulation proceeded at a constant rate for at least 10 min, even when stimulated by 10 mM glutamate in the medium. The calculated control rate of glucose phosphorylation was 2 mmol/kg (dry weight)/min. In the presence of 10 mM glutamate it was twice as great. The response to 10 mM glutamate of different regions of the slice was not uniform, ranging from 164% of control values in the molecular layer of CA1 to 256% in the stratum radiatum of CA1. There was a profound fall in phosphocreatine levels (75%) in response to 10 mM glutamate despite a 2.4-fold increase in glucose phosphorylation. Even in the presence of 1 mM glutamate, the increase in glucose phosphorylation (50%) was not great enough to prevent a significant drop in phosphocreatine content.

Topics: Adenosine Triphosphate; Animals; Brain Edema; Deoxyglucose; Female; Glucose; Glucose-6-Phosphate; Glucosephosphates; Glutamates; Glutamic Acid; Hippocampus; Phosphocreatine; Potassium; Rats

Experimental thermal brain injury leads to significant reduction of glucose utilization in the damaged hemisphere particularly evident in the cortex 3 days after the injury. The rate of development of these changes is not parallel with the observed damage to the blood-brain barrier, coexistent brain oedema and slight disturbances of cerebral blood flow. In a series of experiments it was possible to demonstrate significant accumulation of glucose, high-energy phosphate compounds and their metabolites in the areas of the brain near the damaged part. The authors think that this is an evidence of reduced glucose uptake by the brain resulting from reduced energy needs of the damaged brain tissue despite sufficient supply of energy-yielding substances. Since cerebral metabolism and functions are in close interrelationship reduced glucose metabolism in the damaged tissue leads to reduced activity of the cortex, which contributes to transient (or permanent) functional neurological deficits observed after cranio-cerebral trauma in humans. The knowledge and understanding of these processes regulating the development of local depression of cerebral metabolic processes may help in better results of treatment in such cases.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Diseases, Metabolic; Brain Edema; Cold Temperature; Disease Models, Animal; Female; Glucose; Glycolysis; Male; Phosphocreatine; Rats; Rats, Inbred Strains; Time Factors

Brain oedema is an important aspect of infarction from cerebrovascular occlusion. In a cat stroke model where the middle cerebral artery (MCA) was reversibly or permanently occluded, we analyzed the incidence of fatal hemispheral oedema in 35 normo- (6 mM) and 35 hyperglycaemic (20 mM for 6 hours) animals, with (N = 45) and without (N = 25) restoration of blood flow with clip release at 4 and 8 hrs of occlusion. Fatal hemispheral oedema occurred in 23% of cats (16/70) while hyperglycaemia, for one, and restoration of blood flow, for another, each quadrupled its occurrence. Further, evidence of remote oedema in the form of posterior cingulate cortical pressure atrophy from transtentorial herniation was found in animals that were allowed to survive for 2 weeks and that exhibited infarcts that affected 12 to 95% of the MCA territory. Thus, hemispheral oedema in association with MCA occlusion developed sufficiently markedly as to cause transtentorial herniation in 47% of all cats (33/70). We carried out biochemical analyses in 14 hyper- and 10 normoglycaemic cats after 4 hrs of MCA occlusion for ATP, phosphocreatine (PCr), lactate, glucose and glycogen. The biochemical findings then were correlated with the occurrence of reperfusion oedema following clip release after 4 hrs of occlusion point-by-point in the brains. Linear regression analyses of the brain metabolic and pathologic data revealed highly significant (p less than 0.001) correlations of acute oedema with brain tissue ATP and PCr reductions less than 1.5 microM/g, with lactic acid accumulation greater than 20 microM/g and with the extents of reduction in brain tissue glucose concentrations in the ischaemic territories.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Brain; Brain Edema; Brain Ischemia; Cats; Forecasting; Hyperglycemia; Phosphocreatine; Regression Analysis; Reperfusion

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-D-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.

Topics: Adenosine Triphosphate; Animals; Anticonvulsants; Body Water; Brain; Brain Edema; Brain Injuries; Carbon Dioxide; Cations; Dibenzocycloheptenes; Dizocilpine Maleate; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Oxygen; Phosphates; Phosphocreatine; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Reference Values

The development of symptomatic hyponatremia in otherwise healthy young women can result in death or permanent brain damage. The reasons for the increased female susceptibility to complications from hyponatremia are, however, unclear. To determine whether mechanisms that normally defend the brain against damage from hyponatremia are less effective in females than males, we studied both sodium transport in the brains of hyponatremic male and female rats and the effects of parenteral arginine vasopressin on brain high-energy phosphate metabolism and intracellular pH. Basal sodium uptake in synaptosomes prepared from whole brain of females (2.20 nmol/mg protein) and males (2.98 nmol/mg protein) was not statistically different. In contrast, veratridine-stimulated sodium uptake in female brain was 8.20 nmol/mg protein, which was 86% greater (P less than 0.001) than the 6.12 nmol/mg protein observed for male brain. Additionally, sodium uptake between 5 and 60 s was significantly (P less than 0.001) greater in females than males. These data suggest that the Na+-K+-adenosinetriphosphatase (ATPase) pump function in female rat brain synaptosomes is less effective than in males. To determine whether arginine vasopressin, a peptide hormone that promotes water retention by the kidney, had any effects on cerebral energy metabolism, we performed phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) studies on the brain of normonatremic young adult male and female rats subjected to high (20 IU) peripheral doses of arginine vasopressin. We found decreased high-energy phosphate generation, elevated inorganic phosphate, and intracellular acidosis after arginine vasopressin administration in females but not males.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Arginine Vasopressin; Biological Transport, Active; Brain; Brain Edema; Female; Hyponatremia; Male; Phosphocreatine; Rats; Rats, Inbred Strains; Sex Characteristics; Sodium; Sodium-Potassium-Exchanging ATPase; Synaptosomes

A Remington humane stunner was used to deliver a blow to the left side of the surgically-exposed skull in ketamine-anesthetized cats. At 15 minutes after the trauma, brain tissue was frozen in situ. In animals without visible tissue hemorrhage (Grade 0) and in those with unilateral cerebral contusions involving the cerebral cortex and white matter (Grade 2), regional cerebral metabolite concentrations were measured by enzymatic-fluorometric techniques and edema was tested with an organic gradient. No substantial changes in cerebral metabolite concentrations were observed in head-injured animals without cerebral contusions. In animals with unilateral contusions, the white matter neighboring the tissue hemorrhage had an increase in lactic acid and a decrease in phosphocreatine as compared to values from corresponding areas on the contralateral side, and in control and Grade 0 animals. The cerebral cortex adjacent to tissue hemorrhage had a variable response that ranged from metabolite concentrations within normal ranges to marked decreases in high-energy phosphates and increases in lactic acid. Metabolites of the cortex and white matter contralateral as well as distant to contusion were not statistically different from values of control animals. Changes in several metabolites correlated well with the magnitude of edema. It is concluded that focal metabolic alterations can occur shortly after severe blunt head injury, and that these events may contribute to acute traumatic cerebral edema.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Brain Edema; Brain Injuries; Cats; Glucose; Glycogen; Lactates; Phosphocreatine; Wounds, Nonpenetrating

The bioenergetic mechanisms of vasogenic edema were studied by measuring concentrations of adenosine triphosphate (ATP), phosphocreatine (CrP), and lactate in rapidly frozen edematous white matter in cats. When edema was produced using a cold lesion, it was found that both ATP and CrP were reduced to one-half of control values, and that lactate was elevated. When a correction was applied for dilution, however, it was found that high-energy phosphates were equal to control values, and that lactate was even more significantly elevated. This pattern contrasted with that seen in white-matter ischemia, in which CrP is depressed out of proportion to ATP. Finally, it was found that the white-matter lactate-concentration in the plasma infusion model of edema was increased. It is concluded that vasogenic edema induces an increase in lactate, but does not deplete high-energy phosphate compounds in affected white matter.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Edema; Brain Ischemia; Cats; Cold Temperature; Energy Metabolism; Lactates; Male; Phosphocreatine; Vasomotor System

Topics: Adenosine Triphosphate; Animals; Brain Edema; Cerebrovascular Circulation; Electroencephalography; Energy Metabolism; Evoked Potentials; Humans; In Vitro Techniques; Intracranial Pressure; Lactates; NAD; Phosphocreatine; Rabbits; Reaction Time; Regional Blood Flow; Somatosensory Cortex

Topics: Adenosine Triphosphate; Animals; Brain Chemistry; Brain Edema; Cats; Cerebral Cortex; Cerebrovascular Circulation; Humans; Hydrogen-Ion Concentration; Lactates; Oxygen; Phosphocreatine; Pyruvates; Water

Topics: Adenosine Triphosphate; Animals; Brain Edema; Carbon Dioxide; Cats; Cerebral Cortex; Cerebral Ventricles; Cerebrospinal Fluid; Cisterna Magna; Hydrogen-Ion Concentration; Injections, Intraventricular; Lactates; Oxygen Consumption; Perfusion; Phosphocreatine; Pyruvates; Regional Blood Flow; Water

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Biopsy; Brain Edema; Brain Neoplasms; Cerebral Cortex; Dogs; Energy Metabolism; Female; Freezing; Glycolysis; Humans; Lactates; Male; Methods; Nitrogen; Phosphocreatine; Potassium; Pyruvates; Sodium; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Basal Metabolism; Brain Edema; Cerebral Cortex; Fluorometry; Freezing; Functional Laterality; Glucose; Glycogen; Lactates; Male; Mice; Phosphocreatine

Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Brain Edema; Caudate Nucleus; Cell Membrane; Cerebral Cortex; Chlorides; Dogs; Extracorporeal Circulation; Hypothermia, Induced; Hypoxia, Brain; Osmosis; Oxygen Consumption; Perfusion; Phosphocreatine; Potassium; Rats; Sodium; Water; Water-Electrolyte Balance

Topics: Adenine Nucleotides; Adenosine Triphosphate; Body Fluids; Brain Edema; Brain Neoplasms; Central Nervous System; Cerebral Cortex; Extracellular Space; Glucose; Glycolysis; Humans; Lactates; Phosphates; Phosphocreatine; Pyruvates; Water-Electrolyte Balance

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Animals; Brain; Brain Edema; Carbon Dioxide; Electrolytes; Extracorporeal Circulation; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypothermia; Hypothermia, Induced; Hypoxia; Lactates; Male; Nucleosides; Partial Pressure; Phosphates; Phosphocreatine; Potassium; Pyruvates; Rats; Sodium; Water

Topics: Adenosine Triphosphate; Animals; Brain; Brain Edema; Cerebellum; Cerebral Cortex; Cerebrovascular Circulation; Chlorides; Dogs; Electroencephalography; Extracorporeal Circulation; Female; Hypotension; Hypotension, Controlled; Lactates; Male; Medulla Oblongata; Nucleosides; Perfusion; Phosphocreatine; Potassium; Pyruvates; Sodium; Trimethaphan; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Brain Chemistry; Brain Edema; Carotid Arteries; Dinitrophenols; Glucose; Infusions, Parenteral; Lactates; Male; Models, Biological; Phosphocreatine; Potassium; Rats; Sodium; Water-Electrolyte Balance