Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to clarify the temporal changes of the apparent diffusion coefficients (ADCs) of cerebral metabolites during early focal ischemia using stimulated echo acquisition mode with short echo time at a 7 T magnet to assess the pathophysiology of the reduction in diffusion properties observed both in the ischemic cerebral hemisphere and in the contralateral hemisphere. The ADCs of metabolites in the infarcted hemisphere 1 hour and 3 hours after the onset of ischemia decreased with 25% and 29% for choline containing compounds (Cho), 16% and 26% for creatine and phosphocreatine (Cre), and 19% and 19% for N-acetylaspartate (NAA), respectively, compared with the ADC values 2 hours later in the contralateral hemisphere. There were decreases in the ADC of Cho, Cre, and NAA with 21%, 7%, and 18% 8 hours later, respectively, in the noninfarcted hemisphere, which suggested transhemispheric diaschisis in rats with focal cerebral ischemia. The present study proposed that the diffusion characteristics of the brain metabolites might offer new insights into circulatory and metabolic alteration in the cerebral intracellular circumstance.
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PMID:Temporal changes of the apparent diffusion coefficients of water and metabolites in rats with hemispheric infarction: experimental study of transhemispheric diaschisis in the contralateral hemisphere at 7 tesla. 1077 17

The aim of the present study was to evaluate the use of the endogenous neuronal compound N-acetylaspartate (NAA) as a marker of neuronal damage after focal cerebral ischemia in mice. After occlusion of the middle cerebral artery (MCAO) the ischemic cortex was sampled, guided by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and the NAA concentration was measured by high-pressure liquid chromatography (HPLC). Conventional histology and immunohistological methods using antibodies against neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, glial fibrillary acidic protein (GFAP), and carbodiamide-linked NAA and N-acetylaspartylglutamate (NAAG). The level of NAA rapidly declined to 50% and 20% of control levels in infarcted tissue after 6 hours and 24 hours, respectively. No further decrease was observed during the observation period of 1 week. Within the first 6 hours the number of normal-appearing neurons in the infarcted cortical tissue decreased to 70% of control, of which the majority were eosinophilic. After 24 hours almost no normal-appearing neurons were seen. The number of eosinophilic neurons decreased steadily to virtually zero after 7 days. The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages. This granulomatous material also stained positive for NAA. The number of cells with positive GFAP immunoreactions progressively increased in the circumference of the infarct. They also showed increased immunoreaction against NAA and NSE. The study shows that the level of NAA 7 days after ischemia does not decline to zero but remains at 10% to 20% of control values. The fact NAA is trapped in cell debris and NAA immunoreactivity is observed in the peri-infarct areas restricts its use as a marker of neuronal density.
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PMID:Correlation between N-acetylaspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion. 1082 28

Global brain ischemia provoked by transient occlusion of the carotid arteries (2VO) in gerbils results in a severe loss of neurons in the hippocampal CA1 region. We measured the concentration of the neuron specific N-acetyl-aspartate, [NAA], in the gerbil dorsal hippocampus by proton MR spectroscopy (1H-MRS) in situ, and HPLC, 4 days after global ischemia. The [NAA] was correlated with graded hippocampus damage scoring and stereologically determined neuronal density. A basal hippocampal [NAA] of 8.37+/-0.10 and 9.81+/-0.44 mmol/l were found from HPLC and 1H-MRS, respectively. HPLC measurements of [NAA] obtained from hippocampus 4 days after 2VO showed a 20% reduction in the [NAA] following 4 min of ischemia (P<0.001). 1H-MRS measurements on gerbils subjected to 4 or 8 min of ischemia showed a similar 24% decline in the [NAA] (P<0.05). Thus, there was correlation between the HPLC and 1H-MRS determined NAA decline. There was also a significant correlation between 1H-MRS [NAA] and the corresponding reduction in CA1 neuronal density (P<0.004). In summary our findings show that single voxel 1H-MRS can be used as a supplement to histological evaluation of neuronal injury in studies after global brain ischemia. Accordingly, volume selective spectroscopy has a potential for assessment of neuroprotective therapeutic compounds/strategies with respect to neuronal rescue for delayed ischemic brain damage.
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PMID:Evaluation of CA1 damage using single-voxel 1H-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage? 1117 61

Stroke in children is thought to be a rare phenomenon, but in a pediatric hospital, it is much more common than is expected. The development of rapid MRI imaging with diffusion techniques and MR spectroscopy has brought to the attention of both the neuroradiologists and clinicians that pediatric infarction, in both detection and management, are challenges for the future. Since 1995, cerebral diffusion has been performed at The Children's Hospital of Philadelphia in the evaluation of patients with acute cerebral compromise. Diffusion imaging looks at the motion of water molecules both intra- and extracellular, and the manner in which they become restricted in their motion when higher gradient strength is applied during the imaging sequence. Restricted diffusion is seen in cytotoxic edema, an early acute manifestation of ischemia/infarction. Diffusion studies are often positive when routine MRI and CT are as yet negative. Confirmation of the death of tissue is provided on proton spectroscopy by a rise in lactate from anaerobic glycolysis and a loss of N-acetylaspartate from neuronal death. Confirmation of the diffusion image findings, by mapping the apparent co-efficient (ADC), is also valuable. Application of these techniques, together with magnetic resonance angiography and magnetic resonance venography, is the substance of this paper.
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PMID:Pediatric cerebrovascular disease. 1120 40

Whether proton magnetic resonance spectroscopy (1H-MRS) can be used in the diagnosis of tumorous and nontumorous lesions of the brain was studied. The results of studies were analyzed in 80 patients, including 54 patients with brain tumors (astrocytomas and meningiomas), 20 with nontumorous lesions of the brain, and 6 apparently healthy individuals (controls). The nontumorous lesions of the brain involved cerebral circulatory disorders as ischemia (n = 14) and postradiation changes (n = 6). The studies were performed on a 1.5-T Signa-Horizont magnetic resonance tomograph by using the PROBE/SV programme package. The peak ratios of the following metabolites: N-acetylaspartate (NAA), choline (Cho), creatine, lactate (Lac), lipids (Lip) were examined in the spectra obtained. The spectra of astrocytomas showed a reduced peak of NAA, an elevated peak Cho; there was an increase in the peak of Lac along with higher tumor malignancy stage. The spectra of meningiomas presented a high peak of Cho along with a noticeable reduction in the peaks of other metabolites, the peak of NAA was not visualized. In ischemic lesion of the brain, the peak of Lac appeared within the first hours when the peaks of other metabolites were unchanged. A rise in the peak of Lac and a reduction in that of other metabolites were detectable with time. In radiation-induced lesions, the spectrum displayed a high peak of Lac and the peak of Lip appeared with virtually complete reduction in the peaks of other metabolites. 1H-MRS should be considered as an axillary technique used in combination with routine MRI in the diagnosis of various lesions of the brain, which can estimate chemical compositions, time-course of metabolic changes in the study tissue.
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PMID:[Proton magnetic resonance spectroscopy in diagnostics of tumorous and nontumorous lesions in brain]. 1122 36

Previous studies have shown altered brain metabolism after cerebral hypoxia-ischemia, using magnetic resonance spectroscopy with echo times (TE) of 272 and 136 ms, based on peak-area or peak-height ratios. The present study examined the additional value of proton magnetic resonance spectroscopy with a short TE (31 ms) to predict a poor outcome in neonates with brain hypoxia-ischemia. Studies were performed in 21 full-term neonates with perinatal asphyxia in a 1.5 tesla magnetic field. Proton magnetic resonance spectroscopy was performed in a single volume of interest including the basal ganglia. TE of 272, 136 and 31 ms were used. After curve-fitting procedures, peak-areas as well as peak-height ratios of different brain metabolites were calculated, comparing patients with a poor versus a good outcome. Seven neonates out of 21 had a poor outcome. Neonates with a poor outcome showed a significantly lower N:-acetylaspartate/choline (NAA/Cho) and a significantly raised lactate/NAA (Lac/NAA) ratio using TE of 272 and 136 ms. Using a TE of 31 ms, no differences were found in glutamate/NAA (Glx/NAA), Glx/Cho, myo-inositol/NAA (mI/NAA), and mI/Cho ratios between neonates with a good and those with a poor outcome. Highest predictive values could be achieved for NAA/Cho with a TE of 136 ms. We conclude that low NAA/Cho and high Lac/NAA ratios predict a poor outcome in neonates with cerebral hypoxia-ischemia. TE of 272 and 136 ms have a better predictive value than a TE of 31 ms.
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PMID:Value of (1)H-MRS using different echo times in neonates with cerebral hypoxia-ischemia. 1122 55

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.
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PMID:Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study. 1128 44

Carotid endarterectomy (CEA) is known to be effective in reducing recurrent ischemic attacks, sometimes accompanied with the functional improvement, for patients with internal carotid artery (ICA) flow lesions by increase in perfusion and/or removal of embolic sources. However, the exact mechanism of how the CEA affects the cerebral metabolism in relations to the perfusion increase in noninfarcted hypoperfused peripheral areas to the center of the lesion (e.g., ischemic penumbra or border zone) is not yet clearly known. The existence of the ischemic penumbra and its long-term viability has also been argued. We designed a prospective study to investigate the metabolic changes in the ischemic penumbra for patients with ICA flow lesions and cerebral infarct (or ischemia) before and after CEA using localized in vivo proton magnetic resonance spectroscopy ((1)H-MRS). The results of (1)H-MRS showed significantly decreased choline (Cho)/creatine (Cr) and increased N-acetylaspartate (NAA)/Cho ratios in the periphery of the lesion for the patients after CEA as compared to those who underwent only medical treatments. The more significant changes in the cerebral metabolite levels were observed in the patients who showed the improved cerebral perfusion by single photon emission computed tomography after CEA than in those who did not. In conclusion, our data suggest the existence of the ischemic penumbra, which were viable for a longer period than previously thought; CEA seems to improve the cerebral metabolism that may result from the improved perfusion at the ischemic penumbra.
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PMID:Metabolic changes in the ischemic penumbra after carotid endarterectomy in stroke patients by localized in vivo proton magnetic resonance spectroscopy (1H-MRS). 1142 Jan 59

Sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (CM), suggesting that sequestration causes mechanical obstruction and ischemia. To examine the potential role of ischemia in the pathogenesis of CM, Plasmodium berghei ANKA (PbA) infection in CBA mice was compared to infection with P. berghei K173 (PbK) which does not cause CM (the non-CM model, NCM). Cerebral metabolite pools were measured by (1)H nuclear magnetic resonance spectroscopy during PbA and PbK infections. Lactate and alanine concentrations increased significantly at the terminal stage of CM, but not in NCM mice at any stage. These changes did not correlate with parasitemia. Brain NAD/NADH ratio was unchanged in CM and NCM mice at any time studied, but the total NAD pool size decreased significantly in the CM mice on day 7 after inoculation. Brain levels of glutamine and several essential amino acids were increased significantly in CM mice. There was a significant linear correlation between the time elapsed after infection and small, progressive decreases in the cell density/cell viability markers glycerophosphocholine and N-acetylaspartate in CM, indicative of gradual loss of cell viability. The metabolite changes followed a different pattern, with a sudden significant alteration in the levels of lactate, alanine, and glutamine at the time of terminal CM. In NCM, there were significant decreases with time of glutamate, the osmolyte myo-inositol, and glycerophosphocholine. These results are consistent with an ischemic change in the metabolic pattern of the brain in CM mice, whereas in NCM mice the changes were more consistent with hypoxia without vascular obstruction. Mild obstructive ischemia is a likely cause of the metabolic changes during CM, but a role for immune cell effector molecules cannot be ruled out.
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PMID:Is ischemia involved in the pathogenesis of murine cerebral malaria? 1154 3

2-Phosphonomethyl pentanedioic acid (2-PMPA) is a potent and selective inhibitor of glutamate carboxypeptidase II (NAALADase), and has shown robust neuroprotective activity in both in vitro and in vivo models of ischemia. In the brain, glutamate carboxypeptidase II (GCPII) (EC3.4.17.21) hydrolyzes the neuropeptide N-acetylaspartylglutamate (NAAG) to glutamate and N-acetylaspartate. We report the development and characterization of a [(3)H]2-PMPA binding assay. [(3)H]2-PMPA binding was dependent on protein concentration, saturable, and displaceable. The association (k(on)) and dissociation (k(off)) rate constants were 3x10(6) M(-1) s(-1) and 0.01 s(-1), respectively. The dissociation equilibrium constant (K(d)) determined from the ratio of the rate constants (K(d)=k(off)/k(on)) was 1 nM. Scatchard analysis revealed one binding site with K(d)=2 nM and B(max)=0.7 pmol/mg. Binding exhibited similar pharmacological properties to GCPII enzyme activity, including chloride dependency, cobalt stimulation and inhibition by phosphate and quisqualate. The binding of [(3)H]2-PMPA also showed tissue specificity in that tissues previously reported to be devoid of GCPII enzymatic activity were devoid of [(3)H]2-PMPA binding. [(3)H]2-PMPA binding represents an additional probe for the study of GCPII activity, and may be useful as a high throughput screening assay.
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PMID:Binding of the glutamate carboxypeptidase II (NAALADase) inhibitor 2-PMPA to rat brain membranes. 1155 59


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