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)

Aging is commonly associated with progressive deterioration in central nervous system (CNS) function. Nutritional factors or environmental toxins have important effects on CNS degenerative changes. The blood-brain barrier (BBB) is a major modulator of nutrient delivery to the CNS. The tight junctions and the paucity of pinocytosis or fenestrations in brain capillary endothelium act as an effective barrier between the CNS and the circulating toxic agents. Senescence is associated with significant, though often subtle, changes in BBB. Conditions which are commonly associated with aging, such as hypertension and cerebrovascular ischemia, aggravate the age-related alterations in BBB function. The histologic changes in brain vasculature with aging is region selective and species specific. The common age-related histologic changes include loss of capillary endothelial cells, elongation of the remaining endothelial cells, and decreased capillary diameter in rat cortex, but not in the monkey or human cortex, and a decrease in the number of mitochondria in endothelial cells of the brain capillaries in the monkey but not in the rat. The age-related alterations in BBB transport function include a decrease in BBB choline transport with aging and decreased brain glucose influx. The BBB neutral amino acid transport appears to be unaltered in the aged mice. Most of the studies reported so far have failed to show a significant age-related alteration in BBB permeability to water-soluble substances and high molecular weight solutes in the absence of neurological disease. A more profound change in BBB permeability appears to be associated with Alzheimer's disease. Immunohistological studies have demonstrated the presence of serum proteins in the cerebrovascular amyloid in patients with Alzheimer's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of aging on the blood-brain barrier. 328 93

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
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PMID:Senile dementia of the Alzheimer type. 613 75

Positron computed tomography is a noninvasive medical imaging technique. Biologically active, radiolabeled compounds are administered intravenously to patients and the distribution of the radioactivity is quantitatively measured. By using appropriate mathematical models and labeled compounds, quantitative measurements of local metabolism, blood flow and volume, protein synthesis, transport, receptor binding, drug kinetics, and concentrations can be obtained noninvasively. This technique goes beyond medical imaging; it allows local analytic assays of biochemical reactions. In the heart, the technique measures local blood flow as well as myocardial free fatty acid and glucose metabolism, and can clinically evaluate patients with ischemic heart disease or cardiomyopathies. In the brain, positron computed tomography can be used to examine alterations in blood flow and metabolism including ischemia and degenerative disorders (Huntington's disease and Alzheimer's disease), cerebral tumors, and epilepsy. In normal persons, positron computed tomography shows cerebral activations resulting from physiologic stimulation (auditory and visual).
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PMID:Positron computed tomography for studies of myocardial and cerebral function. 621 2

This review describes insults to the brain which result in either an increased or decreased mass effect. These mechanisms produce certain derangements in the central nervous system, which can lead to the patient's death. Increased intracranial mass effect characterized by brain tumors may produce lethal brain-stem ischemia. On the other hand, decreased intracranial mass effect as seen in Alzheimer's disease leads to aspiration pneumonia and terminal sepsis.
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PMID:A neuropathologic approach to human disease: the intracranial mass effect. 703 53

The distribution of beta-amyloid protein precursor (APP) was investigated immunocytochemically in rats subjected to global cerebral ischemia (GCI) induced by cardiac arrest. Rats underwent 10 min of GCI with 3, 6, and 12 h and 2 and 7 days of survival. APP immunostaining was found extracellular and intracellularly. Multiple extracellular APP immunoreactive deposits around and close to the vessels appeared as soon as 3 h after GCI. Extracellular accumulation of APP occurred frequently in the hippocampus, cerebral and cerebellar cortex, basal ganglia and thalamus and rarely in the brain stem. These deposits were labelled with antibodies against the N-terminal, beta-amyloid peptide, and C-terminal domains of APP. Our data suggests that either proteolytically cleaved fragments of the full-length APP or the entire APP molecule accumulates extracellularly after GCI. This findings may not only implicate the participation of APP in postischemic tissue damage but also suggest the involvement of pathomechanisms operating in ischemia in Alzheimer's disease pathology.
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PMID:Complete cerebral ischemia with short-term survival in rats induced by cardiac arrest. I. Extracellular accumulation of Alzheimer's beta-amyloid protein precursor in the brain. 752 11

In order to characterize the regional and cellular distribution patterns of individual ionotropic excitatory amino acid receptor subunits in the human hippocampus we performed an immunohistochemical analysis using the monoclonal antibody 3A11 to the AMPA GluR2(4) subunit. The study was based on paraffin embedded hippocampal specimens of five human brains obtained at autopsy. GluR2(4) immunoreactivity was consistently higher in hippocampus as compared to the adjacent areas of the mesial temporal lobe. Virtually all neurons showed intracytoplasmic staining of the perikarya and dendritic profiles with well defined laminar patterns. The most intense GluR2(4) immunoreactivity was observed in the target structures of mossy fibers, thus indicating that GluR2(4) AMPA subunits may be involved in NMDA-independent synaptic transmission pathways and long-term potentiation. Glial cells were not immunoreactive. These findings may provide basic information for studies of the GluR2(4) subunit in human hippocampus during various neuropathological conditions, such as temporal lobe epilepsy, ischemia and Alzheimer's disease.
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PMID:Regional distribution of the AMPA glutamate receptor subunits GluR2(4) in human hippocampus. 755 21

Oxygen-based free radicals have been shown to play a major role in the acute destruction of neurons following cerebral ischemia and may be involved in the chronic neurodegeneration seen in Parkinson's disease, Alzheimer's disease, and other conditions characterized by the progressive death of neurons in the central nervous system. Drugs belonging to a group of antioxidant compounds, collectively known as the lazaroids, have strong neuroprotective effects in experimental models of acute ischemia. However, the specific mechanisms by which these drugs reduce the harmful actions of free radicals have not been established. Using electron paramagnetic resonance (EPR) spectroscopy with spin trapping, we investigated the interaction of U-74500A, a first-generation lazaroid, and U-78517F, a second-generation lazaroid, with two species of oxygen-based free radicals in aqueous solution and with the stable nitrogen-based free radical diphenylpicrylhydrazyl in dimethyl sulfoxide. Superoxide radicals were generated by the action of xanthine oxidase on hypoxanthine. Hydroxyl radicals were generated by the Fenton reaction involving aqueous ferrous iron and hydrogen peroxide. Both lazaroids reduce the EPR signal of all three radicals, but the drugs differ in potency and relative radical selectivity. These observations are consistent with the lazaroids being scavengers of oxygen-based and nitrogen-based free radicals and suggest that the neuroprotective actions of the lazaroids in cerebral ischemia may involve direct interactions of the lazaroids with several different species of free radicals.
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PMID:An in vitro EPR study of the free-radical scavenging actions of the lazaroid antioxidants U-74500A and U-78517F. 763 55

N-Methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity may depend, in part, on the generation of nitric oxide (NO.) and superoxide anion (O2.-), which react to form peroxynitrite (OONO-). This form of neurotoxicity is thought to contribute to a final common pathway of injury in a wide variety of acute and chronic neurologic disorders, including focal ischemia, trauma, epilepsy, Huntington disease, Alzheimer disease, amyotrophic lateral scelerosis, AIDS dementia, and other neurodegenerative diseases. Here, we report that exposure of cortical neurons to relatively short durations or low concentrations of NMDA, S-nitrosocysteine, or 3-morpholinosydnonimine, which generate low levels of peroxynitrite, induces a delayed form of neurotoxicity predominated by apoptotic features. Pretreatment with superoxide dismutase and catalase to scavenge O2.- partially prevents the apoptotic process triggered by S-nitrosocysteine or 3-morpholinosydnonimine. In contrast, intense exposure to high concentrations of NMDA or peroxynitrite induces necrotic cell damage characterized by acute swelling and lysis, which cannot be ameliorated by superoxide dismutase and catalase. Thus, depending on the intensity of the initial insult, NMDA or nitric oxide/superoxide can result in either apoptotic or necrotic neuronal cell damage.
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PMID:Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. 763 61

The CA1 region of hippocampus is selectively vulnerable to a variety of insults, including hypoxia-ischemia and Alzheimer's disease, but the basis of this regional susceptibility is poorly understood. We examined the regional hippocampal sensitivity to mitochondrial metabolic disruption induced by malonate, an inhibitor of succinate dehydrogenase. The CA1 region was exquisitely sensitive to malonate and the dentate gyrus was extremely resistant; the CA3 region had intermediate sensitivity. This pattern of vulnerability is reminiscent of hypoxic-ischemic damage. Malonate damage was blocked by the N-methyl-D-aspartic acid (NMDA) antagonist, MK-801, but regional susceptibility to malonate did not correlate with the density of NMDA receptors. Instead, malonate toxicity was inversely correlated with activity of succinate dehydrogenase. Our results suggest that regional metabolic capacity may help to determine sensitivity to metabolic/excitotoxic insults such as hypoxia-ischemia.
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PMID:Selective vulnerability of the CA1 region of hippocampus to the indirect excitotoxic effects of malonic acid. 767 3

To investigate the relationship between troublesome behavior and cognitive status in Alzheimer type dementia (DAT), and to know whether the addition of cerebrovascular ischemia modifies that relationship, we studied behavioral and cognitive data from a clinical series of 57 DAT patients (mean age: 83.4 yrs) and 31 patients with mixed Alzheimer and vascular dementia (MIX) (mean age: 83.4 yrs). All subjects were ambulatory and were recruited from among patients having been admitted to our affiliated nursing home. None of them had any serious systemic diseases. The Dementia Behavior Disturbance scale (DBD), originally developed by Baumgarten et al, and the Mini-Mental State (MMS) were used for the evaluation of behavioral problems and cognitive status, respectively. In the DAT group, a significant correlation was recognized between DBD and MMS scores. In the MIX group, however, DBD scores did not correlate with MMS scores. Among patients having MMS scores greater or equal to 20, those with MIX had higher DBD scores (mean 19.3) than those with DAT (mean 13.7), although MMS scores in these two subgroups were comparable. These findings suggest that in DAT, behavioral problems increase in conjunction with cognitive impairments. However, with the addition of cerebrovascular ischemia to Alzheimer pathology, behavioral impairments may progress independently of cognitive decline, with more frequent presentation of troublesome behaviors in the early stage of dementia.
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PMID:[Relationship between behavioral problems and cognitive status in Alzheimer type and mixed Alzheimer and vascular dementia]. 772 88


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