phosphocreatine and Cerebrovascular-Disorders

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

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

Mimicking in rats the reduced level of dietary magnesium (Mg) intake, seen in present-day Western World populations, short-term (4 weeks) restriction of Mg intake (30-35% normal) resulted in a 40% loss in brain intracellular free Mg2+ ions ([Mg2+]i) and significant rises in brain intracellular pH (pHi) and phosphocreatine ([PCr]) but no change in [ATP] or [Pi] as measured by 31P-NMR spectroscopy. Such Mg-deficient animals (serum Mg fell 65%), when given ED40 stroke doses of ethanol, demonstrated a 100% stroke mortality. These findings indicate that: 1) moderate, short-term Mg deficiency makes the brain vulnerable to hypoxic-lethal stroke insults induced by alcohol administration, and 2) brain [Mg2+]i appears to play an important role in finely regulating brain pHi and [PCr].

Topics: Animals; Brain; Brain Injuries; Cerebrovascular Disorders; Diet; Ethanol; Hydrogen-Ion Concentration; Magnesium; Magnesium Deficiency; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Rats; Rats, Wistar

A hybrid of two localized spectroscopy techniques, chemical shift imaging (CSI) and Hadamard spectroscopic imaging (HSI), is used to obtain an array of 16 x 16 x 4 (3 x 3 x 3 cm3 voxels) proton-decoupled phosphorus (31P) spectra of human brain. For equal spatial resolution, this organ's oblate shape requires fewer axial than coronal or sagittal slices. These different spatial requirements are well suited to 1D, 4th order, transverse HSI in the axial direction, combined with 2D 16 x 16 CSI in the other two orientations. The reduced localization matrix (16 x 16 x 4 over just the brain versus a cubic-16 x 16 x 16 matrix of equal resolution, over the entire head) may proportionally shorten data acquisition if the voxel size is not signal-to-noise limited. In addition, the use of Hadamard encoding can improve the intervoxel spectral isolation.

Topics: Aged; Algorithms; Artifacts; Brain; Cerebrovascular Disorders; Feasibility Studies; Humans; Hydrogen; Image Enhancement; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Models, Structural; Muscle, Skeletal; Phosphocreatine; Phosphorus Isotopes

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

The effect of chronic low- and high-dose treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on the development of hypertension and left ventricular hypertrophy as well as on functional and biochemical alterations of the heart was studied in stroke-prone spontaneously hypertensive rats treated prenatally and subsequently up to the age of 20 weeks. The contribution of endogenous bradykinin potentiation to the ACE inhibitor actions was assessed by cotreatment of rats with the bradykinin B2-receptor antagonist Hoe 140 (500 micrograms/kg per day SC) from 6 to 20 weeks of age. High- but not low-dose ACE inhibitor treatment prevented the development of hypertension and left ventricular hypertrophy. Chronic bradykinin receptor blockade did not attenuate the antihypertensive and antihypertrophic actions of ramipril. High-dose ramipril treatment improved cardiac function, as demonstrated by an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and coronary flow (22.1%), without a change in heart rate. The activities of lactate dehydrogenase and creatine kinase and lactate concentration in the coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatment led to a pattern of changes in cardiodynamics and cardiac metabolism similar to that observed with the high dose. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by chronic bradykinin receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Administration, Oral; Animals; Bradykinin; Cerebrovascular Disorders; Coronary Circulation; Creatine Kinase; Dose-Response Relationship, Drug; Female; Glycogen; Heart; Hypertension; Hypertrophy, Left Ventricular; L-Lactate Dehydrogenase; Lactates; Male; Myocardium; Phosphocreatine; Pregnancy; Ramipril; Rats; Rats, Inbred SHR; Rats, Wistar; Ventricular Pressure

We examined metabolic and functional changes when forebrain ischemia was induced in stroke-prone spontaneously hypertensive rats by bilateral carotid artery occlusion. In addition, the protective effect of clentiazem was evaluated in this model.. Rats were anesthetized with urethane. Cerebral blood flow was measured with a laser Doppler flowmeter. Cerebral high-energy phosphates and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Electroencephalographic activity was evaluated as the summation of its amplitude. These parameters were monitored during a 30-minute period of ischemia and recirculation. Clentiazem was given orally as pretreatment (10 mg/kg twice a day for 3.5 days).. Bilateral carotid occlusion caused a decrease in cerebral blood flow to approximately 5% of the preischemic level and the disappearance of electroencephalographic activity. Occlusion also caused a decrease in ATP and phosphocreatine (to 48.7 +/- 4.3% and 23.7 +/- 2.2% of preischemic levels, respectively) as well as intracellular pH (from 7.3 +/- 0.1 to 6.0 +/- 0.1). During recirculation the reversal of these changes was variable: high-energy phosphates were partially restored, but electroencephalographic activity and intracellular pH showed little improvement. Hypoperfusion (55.7 +/- 11.5% of the preischemic flow) developed after reactive hyperemia. Pretreatment with clentiazem lessened the decrease in cerebral blood flow (control, 4.8 +/- 1.4%; clentiazem, 14.1 +/- 4.1% of the preischemic level; P < .05) and prevented the disappearance of electroencephalographic activity in some rats during ischemia. Clentiazem also prevented postischemic hypoperfusion and accelerated the restoration of high-energy phosphates, intracellular pH, and electroencephalographic activity during recirculation.. Carotid artery occlusion induced stable forebrain ischemia in stroke-prone spontaneously hypertensive rats. Clentiazem improved the metabolic and functional disturbances that occurred in this ischemic model, and its beneficial effect appeared to be due mainly to the relative preservation of cerebral blood flow during carotid occlusion.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Antihypertensive Agents; Arterial Occlusive Diseases; Blood Pressure; Brain; Brain Ischemia; Carbon Dioxide; Carotid Artery Diseases; Cerebral Arteries; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Diltiazem; Disease Susceptibility; Electroencephalography; Energy Metabolism; Heart Rate; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Oxygen; Partial Pressure; Phosphocreatine; Rats; Rats, Inbred SHR; Regional Blood Flow; Time Factors; Tissue Distribution

We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.

Topics: Adenosine Triphosphate; Aged; Brain; Cerebrovascular Disorders; Humans; Hydrogen-Ion Concentration; Intracellular Fluid; Ischemic Attack, Transient; Magnesium; Magnetic Resonance Spectroscopy; Middle Aged; Phosphocreatine; Phosphorus

Localized proton nuclear magnetic resonance spectroscopy (MRS), obtained with stimulated echo and spin echo sequences, MR imaging (MRI) and MR angiography (MRA) were used to study the brain in 13 children and adolescents with sickle cell disease. Regions of interest (ROI) studied by MRS included regions appearing normal on MRI as well as regions showing complications of sickle cell disease, including focal deep white matter areas of high signal intensity (deep white matter ischemia, DWMI) seen on long TR images, focal atrophic brain areas, and infarcts. The findings in these studies are summarized as follows: Normal-appearing regions on MRI have normal MRS. In ROI including small areas of DWMI, lactate elevation was not detected, but the levels of N-acetyl-aspartate (NAA) appeared slightly elevated. In areas of DWMI 1-2 cm in size, reduced blood flow could be seen on MRA and lactate elevation could be detected with MRS. When blood flow to a DWMI region was normal, NAA was reduced and there was little lactate elevation, as cell death had already occurred. ROI consisting of atrophic tissue had reduced NAA levels but total creatine levels were not changed. Sometimes lipids, presumably from broken cell membrane, could be detected. In regions of past massive stroke, all metabolites were absent except for small amounts of lactate or lipids.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Aspartic Acid; Atrophy; Brain; Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Child; Choline; Creatine; Female; Frontal Lobe; Humans; Hydrogen; Lactates; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine

The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period.

Topics: Acidosis; Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Brain; Cerebral Infarction; Cerebrovascular Disorders; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Ischemic Attack, Transient; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphates; Phosphocreatine; Phosphorus

31P-NMR spectroscopic studies were performed in vivo on brains of rats administered cocaine. Cocaine.HCl (1-5 mg/kg) administered systemically to lightly anesthetized rats resulted in significant and progressive deficits in whole brain intracellular free Mg ([Mg2+]i). Intracellular pH (pHi) also fell in a progressive manner but only after a significant fall in brain [Mg2+]i was noted. Both [Mg2+]i and pHi returned to normal in most rats. Brains of rats that exhibited stroke-like events, however, demonstrated continued intracellular acidosis associated with progressive loss of phosphocreatine and elevation of Pi up until death. These observations are consistent with the tenet that injection of cocaine can result in severe cerebral vasospasm, ischemia and rupture of cerebral blood vessels as a consequence of depletion of brain [Mg2+]i.

Topics: Animals; Brain Chemistry; Brain Ischemia; Cerebrovascular Disorders; Cocaine; Hydrogen-Ion Concentration; Magnesium Deficiency; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Rats; Rats, Wistar

The early time course after acute stroke of cerebral N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy.. Eight patients with acute stroke were studied serially in the acute phase, 1 week after, and 2-4 weeks after the onset of clinical symptoms. Ten healthy volunteers served as controls. A stimulated echo (STEAM) sequence was used for measurement of the brain metabolites in a volume of interest located within the infarcted area as visualized by magnetic resonance imaging. For quantification, the unsaturated water signal was used as the internal standard. Regional cerebral blood flow in the infarcted area was measured relative to a symmetrically located unaffected area by means of single-photon emission computed tomographic scanning, using 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as the flow tracer.. Relative regional cerebral blood flow was considerably reduced in the infarcted area in the acute phase. After 1 week, hyperemia was seen in all but one patient. The N-acetylaspartate content was significantly reduced, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N-acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change was seen in the choline content.. Assuming that N-acetylaspartate content reflects neuronal survival or loss, our results may suggest that treatment procedures with restoration of blood flow to severely ischemic areas should be initiated within the first 6 hours after stroke onset.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Aspartic Acid; Brain Chemistry; Cerebrovascular Circulation; Cerebrovascular Disorders; Choline; Creatine; Humans; Magnetic Resonance Imaging; Middle Aged; Phosphocreatine; Time Factors; Tissue Distribution

Four patients were observed serially with 1H magnetic resonance spectroscopy (MRS) at times ranging from 3 days to 10 weeks after a documented ischemic event. Spectra were obtained from 8 cc volumes in infarcted regions and contralateral matched normal regions. Reproducible variations in n-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and the sequential changes in lactate and lipid resonances are related to the pathophysiology of stroke. A conspicuous lack of significant change in the choline (Cho) resonance with concomitant decrease in NAA and Cr + PCr is reported as a possible marker of ischemic injury.

Topics: Aged; Aspartic Acid; Brain; Cerebrovascular Disorders; Choline; Creatine; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Time Factors

The energy metabolism of the brain has been measured in a middle cerebral artery (MCA) occlusion model in the cat utilizing 31P-nuclear magnetic resonance (NMR). 31P-NMR spectra were serially obtained during 2 h of ischemia and a subsequent 4-h recovery period. The ratio of creatine phosphate (PCr) to inorganic phosphate (Pi) (PCr/Pi) showed a precipitous decrease in parallel with changes in electroencephalographic (EEG) amplitude in severe strokes during ischemia as well as during recirculation. Animals with mild strokes, as determined by EEG criteria, exhibited a much smaller decrease in PCr/Pi during ischemia. In the severe strokes, there was a splitting and significant shift of the Pi peak immediately after occlusion. In addition, the shifted Pi peak rapidly increased and remained elevated throughout the study. In the mild strokes, Pi also increased, but not as markedly. Intracellular pH determination by chemical shift of the Pi peak revealed a decrease from 7.1 to 6.2-6.3 during ischemia and the subsequent recovery period in the animals with severe strokes, whereas the pH in the animals with mild strokes did not show a significant change. A gradual decrease in adenosine triphosphate (ATP) to 57-79% of the control was exhibited in severely stroked animals during both the ischemia and the recovery period, whereas there was no change in ATP in the mild stroked animals. These results suggest that the dynamic process of pathophysiological changes in an MCA occlusion model in the cat leads to significant differences in cerebral metabolism between animals with mild and severe strokes.

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Brain; Cats; Cerebral Arterial Diseases; Cerebrovascular Disorders; Electroencephalography; Energy Metabolism; Male; Phosphates; Phosphocreatine; Phosphorus

Topics: Adenosine Triphosphate; Animals; Brain Death; Cerebrovascular Disorders; Electrophysiology; Glucose; Guinea Pigs; Ischemia; Lactates; Limbic System; Phosphocreatine; Synaptic Transmission; Time Factors

Topics: Acid-Base Equilibrium; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Brain; Carbon Dioxide; Cerebrovascular Disorders; Electroencephalography; Energy Metabolism; Glucose; Glycogen; Hydrogen-Ion Concentration; Infarction; Lactates; Male; Oxygen; Phosphocreatine; Pyruvates; Rats; Rats, Inbred Strains; Time Factors; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Blood Glucose; Brain; Cerebrovascular Disorders; Glucose; Glycogen; Hexosephosphates; Hypoxia, Brain; Ischemia; Lactates; Mice; Phosphocreatine