Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the contribution of cellular dysfunction and neuronal loss to brain N-acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV detection in rats subjected to cerebral injury, associated or not with cell death. When lesion was induced by intracarotid injection of microspheres, the fall in NAA was related to the degree of embolization and to the severity of brain oedema. When striatal lesion was induced by local injection of malonate, the larger the lesion volume, the higher the NAA depletion. However, reduction of brain oedema and striatal lesion by treatment with the lipophilic iron chelator dipyridyl (20 mg/kg, 1 h before and every 8 h after embolization) and the inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h before malonate and then every 9 h), respectively, failed to ameliorate the fall in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a marked reversible fall in NAA striatal content was observed despite the lack of tissue necrosis. Overall results show that cellular dysfunction can cause higher reductions in NAA level than neuronal loss, thus making of NAA quantification a potential tool for visualizing the penumbra area in stroke patients.
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PMID:N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury. 1129 3

Excessive glutamatergic transmission is thought to be responsible for the injury observed in a variety of neurological disorders such as stroke. N-acetylaspartylglutamate (NAAG), a major peptidic component of the brain, has been suggested to serve as a potential storage form of glutamate. N-acetylated-a-linked acidic dipeptidase (NAALADase, EC 3.4.17.21) is responsible for the hydrolysis of NAAG into N-acetylaspartate (NAA) and glutamate. If NAAG is a storage form of glutamate, then inhibition of NAALADase should be neuroprotective in diseases in which excess glutamatergic transmission is detrimental. In addition, NAAG has been demonstrated to be an agonist at group II metabotropic glutamate receptors and functions as a mixed agonist/antagonist at N-methyl-D-aspartate receptors. Therefore, inhibition of NAALADase would also function to increase NAAG levels which, in turn, should provide neuroprotection via the interaction of NAAG with these receptors. Recently, potent and selective inhibitors of the enzyme have been designed and subsequently used to demonstrate that inhibition of NAALADase is neuroprotective in animal models of neurodegeneration. As such, NAALADase inhibition represents a novel method of regulating extracellular glutamate levels and provides a new avenue for the treatment of neurological disorders.
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PMID:Design of NAALADase inhibitors: a novel neuroprotective strategy. 1137 62

Cerebral tissue with T2 magnetic resonance imaging (MRI) abnormalities following stroke is generally considered infarcted, while surrounding regions with normal MRI appearance are believed to be healthy. To assess whether these surrounding regions consist of normal tissue, we explored the distribution of N-acetylaspartate (NAA) and lactate within and around the hyperintense area on T2-weighted MRI using proton MR spectroscopy. The study was carried out in 25 patients with middle cerebral artery occlusion imaged between 1 and 42 days after stroke onset. NAA/choline (Cho) ratios were significantly reduced in both areas of T2 hyperintensity and in surrounding tissue. The reduction was greater in the region of T2 hyperintensity than in the surrounding region (-50% vs. -28%, respectively) and was unrelated to the delay after the ictus. Lactate/Cho ratios increased massively within the abnormal T2 area, but did not differ from control values beyond the margin of hyperintensity. Overall data indicate that T2 visible lesions on MRI do not infer the entire injured tissue.
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PMID:Spectroscopic data following stroke reveal tissue abnormality beyond the region of T2-weighted hyperintensity. 1208 46

Changes in metabolites detected by proton magnetic resonance spectroscopy ((1)H MRS) of the brain have been demonstrated in Alzheimer's disease. Our objectives were, first, longitudinally to measure absolute concentrations of metabolites in both hippocampi, the sites of early Alzheimer's disease, in patients with clinical Alzheimer's disease and controls; secondly, to separate the relative contribution of atrophy and metabolite concentration change to overall signal change; and, thirdly, to determine whether metabolite concentrations in the hippocampus relate to cognitive scores. (1)H MR spectra were acquired from a single voxel (12 x 15 x 25 mm(3) = 4.5 ml) aligned to the long axis of each hippocampus in nine probable or possible Alzheimer's disease subjects diagnosed according to the National Institute of Neurologic and Cognitive Disorders and Stroke (NINCDS) compared with 14 age-matched NINCDS-negative Alzheimer's disease controls. Metabolite concentrations were corrected for the amount of CSF present in the voxel. Hippocampal volumes were measured at the same time. The same protocol was repeated approximately 1 year later. We found that atrophy-corrected hippocampal N-acetylaspartate (NAA) concentration was lower in cognitively impaired subjects compared with controls. This was significant for the left hippocampus (baseline 87% of control, P = 0.013; and at 1 year 76% of control, P = 0.020). Hippocampal volumes also differed significantly between the groups, and decreased significantly over 1 year in the Alzheimer's disease group (12%, P = 0.017). The decrease in [NAA] over 1 year was not significant in either group. Discriminant analysis revealed that the best classification of subjects was by including both left NAA concentration and left hippocampal volume. myo-Inositol signals from these small voxels had poor signal-to-noise and demonstrated no significant changes. We conclude that (1)HMRS-detectable metabolites can be quantified from the hippocampi of cognitively impaired individuals, and that hippocampal [NAA] is significantly reduced in Alzheimer's disease, in excess of atrophy. In our cohort, the differences were more significant for the left hippocampus.
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PMID:Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease. 1224 89

The annual risk of stroke in patients with symptomatic carotid artery occlusion (CAO) and impaired cerebral blood flow (CBF) is approximately 10%. Increased oxygen extraction fraction measured by positron emission tomography (PET) and low cerebrovascular reactivity assessed by transcranial Doppler is associated with an increased risk of recurrent ischemic stroke in these patients. Recently, other risk factors have been identified: (1) symptoms of purported hemodynamic origin; (2) ongoing symptoms in the presence of documented symptomatic CAO; (3) leptomeningeal collaterals visible on angiography; and (4) low NAA/choline ratio on magnetic resonance (MR) spectroscopy. Evidence is growing that a second extracranial-intracranial (EC-IC) bypass trial might be worthwhile in patients with symptomatic CAO. Probably, only patients with ongoing symptoms and compromised CBF should be included in such a trial. Current evidence based therapeutic options for patients with symptomatic CAO include antithrombotic medication and control of vascular risk factors. For stenosis of the contralateral internal or ipsilateral external carotid artery endarterectomy may be considered. Ongoing symptoms may cease after tapering of antihypertensive medication.
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PMID:Management of patients with symptomatic carotid artery occlusion. 1245 Feb 38

Using different models of focal cerebral ischemia, the temporal and spatial rules of metabolism and energy changes in the post-ischemia brain tissue were measured by proton magnetic resonance spectroscopy (1HMRS) to provide valuable information for judging the prognosis of acute focal cerebral ischemia and carrying out effective therapy. Nine healthy Sprague-Dawly rats (both sexes) were randomly divided into two groups: The rats in the group A (n = 4) were occluded with self-thrombus for 1 h; The rats in the group B (n = 5) were occluded with thread-emboli for 1 h. The 1H MRS at 30, 40, 50, 60 min respectively was examined and the metabolic changes of NAA, Cho and Lac in the regions of interest were semiquantitatively analyzed. The spectrum integral calculus area ratio of NAA, Cho, Lac to Pcr + Cr was set as the criterion. The values of NAA.Cho in the regions of interest were declined gradually within 1 h after ischemia, especially, the ratio of Cho/(Pcr + Cr), NAA/(Pcr + Cr) at 60 min had significant difference with that at 50 min (P < 0.05). The ratio of Lac/(Pcr + Cr) began to decrease at 40 min from initial increase of Lac in both A and B groups. MR proton spectrum analysis was a non-invasive, direct and comprehensive tool for the study of cellular metabolism and the status of the biochemical energy in acute ischemia stroke.
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PMID:An experimental proton magnetic resonance spectroscopy analysis on early stage of acute focal cerebral ischemia. 1267 80

Magnetic resonance imaging (MRI) of diffusion and magnetization transfer was combined with 1H-spectroscopic imaging (CSI) to evaluate the clinical potential of in-vivo profiles of various brain pathologies. Ten patients (multiple sclerosis, cerebrovascular disease, leukodystrophy, Alzheimer dementia) and five healthy volunteers were investigated with diffusion-weighted MRI, magnetization transfer imaging, and CSI. Proton spectra were analyzed as ratios of NAA/Cr and Cho/Cr calculated from the peak areas of N-acetylaspartate (NAA), (phospho)-creatine (Cr) and choline (Cho). The apparent diffusion coefficient (ADC) and the magnetization transfer ratio (MTR) were determined in identical voxels to ensure identical partial volume effects compared to CSI. Compared to MTR and ADC assessments, the lower spatial resolution of CSI clearly indicates a hindrance at 1.5 T. In most demyelinating lesions, NAA/Cr reduction paralleled attenuated MTRs and elevated ADCs. By contrast, in acute stroke and some acute MS lesions the ADC was reduced, while MTR and NAA/Cr were also decreased. In Alzheimer's dementia, ADC was increased, MTR unchanged and Cho/Cr increased. In a case of leukodystrophy, ADC was pronouncedly increased, MTR and NAA/Cr both reduced, and Cho/Cr normal. Combined measurements of ADC, MTR and CSI are feasible and provide differential in-vivo information on various brain pathologies.
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PMID:Combined MR measurements of magnetization transfer, tissue diffusion and proton spectroscopy. A feasibility study with neurological cases. 1273 41

Monitoring the signal levels of lactate (Lac) and N-acetylaspartate (NAA) by chemical shift imaging can provide additional knowledge about tissue damage in acute stroke. Despite the need for this metabolic information, spectroscopic imaging (SI) has not been used routinely for acute stroke patients, mainly due to the long acquisition time required. The presented data demonstrate that the application of a fast multiple spin-echo (MSE) SI sequence can reduce the measurement time to 6 min (four spin echoes per echo train, 32 x 32 matrix). Quantification of Lac and NAA in terms of absolute concentrations (i.e., mmol/l) can be achieved by means of the phantom replacement approach, with correction terms for the longitudinal and transversal relaxation adapted to the multiple spin-echo sequence. In this pilot study of 10 stroke patients (symptom onset < 24 hr), metabolite concentrations obtained from MSE-SI add important information regarding tissue viability that is not provided by other sequences (e.g., diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI)). Metabolic changes extended beyond the borders of the apparent diffusion coefficient (ADC) lesion in nine of the 10 patients, showing a rise in Lac concentrations up to 18 mmol/l, while NAA levels sometimes dropped below the detection level. Considerable differences among the patients in terms of the Lac concentrations and the size of the SI-ADC mismatch were observed.
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PMID:Multiple spin-echo spectroscopic imaging for rapid quantitative assessment of N-acetylaspartate and lactate in acute stroke. 1528 4

The present review examines and discusses the changes in N-acetylaspartate (NAA) concentration in the ischaemic brain from the existing literature of animal research. By summarizing the current knowledge on NAA metabolic pathways and reviewing the data obtained in animal models of global and focal ischaemia, the following conclusions emerge from this compilation: (i) both magnetic resonance spectroscopy (MRS) and the absolute HPLC method of NAA quantification give converging information; (ii) decreases in brain NAA concentration in acute stroke can be considered as an index of neuronal loss or dysfunction, although NAA redistribution by glial cells and NAA trapping in cell debris restrict its use as a quantitative neuronal marker; (iii) further studies on NAA metabolism in pathologic brain are required before using NAA measurement in the chronic stage of ischaemia for evaluating neuroprotective strategies.
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PMID:N-acetylaspartate: a literature review of animal research on brain ischaemia. 1528 82

The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.
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PMID:1H MRS in stroke patients with and without cognitive impairment. 1571 46


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