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)

Growth inhibitory factor (GIF) has been identified as a new metallothionein-like protein, the level of which is decreased in the Alzheimer's disease brain. GIF and glial fibrillary acidic protein (GFAP) have been reported to be expressed in reactive astrocytes in the rat brain following stab wounds. Moreover, strong expression of GIF mRNA in reactive astrocytes after ventricular injection of kainic acid has been demonstrated. To clarify the biological functions of GIF and GFAP in repair of the CNS, we examined changes in their relative levels to sham control using a Western blotting technique in the rat left hemisphere following occlusion of the left middle cerebral artery, for 28 days after surgery. The GIF relative level declined to 56% of the sham-operated control value on day 7. Thereafter the GIF relative level increased and returned to the normal relative level by days 21-28. The GFAP relative level increased from day 3 and reached a maximum of 120% of the sham-operated control value on days 14-21. While GIF and GFAP were both detected in reactive astrocytes, an increase in the GFAP relative level occurred prior to an increase in GIF relative level following the ischemia. The patterns of changes in relative expression levels of GIF and GFAP were quite similar to those in our previous studies on effects of cerebral stab wounds in rats, although the changes were more rapid in the previous studies. GIF and GFAP appear to play different roles in the repair of the CNS. The present results also indicated that GIF could play an important role in CNS repair after cerebral ischemia and provide new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP.
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PMID:Patterns of growth inhibitory factor (GIF) and glial fibrillary acidic protein relative level changes differ following left middle cerebral artery occlusion in rats. 886 68

The original notion that the brain represented an "immune-privileged" organ lacking the capability to produce an inflammatory response to an injury, would appear no longer tenable. Indeed, accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory response to a variety of insults including trauma, ischemia, transplantation, viral infections, toxins as well as neurodegenerative processes. Many aspects of this centrally-derived inflammatory response parallel, to some extent, the nature of such a reaction in the periphery. Through the recent application of molecular biological techniques, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNF alpha and IL-1 beta, as well as adhesion molecules, has been emphasized in the propagation and maintenance of a CNS inflammatory response. This review will summarize recent observations as to the involvement of these inflammatory mediators in CNS injury and lay claim to the possibility that inhibitors of peripheral inflammation may also be of benefit in treating CNS injuries such as stroke, head trauma, Alzheimer's disease and multiple sclerosis.
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PMID:The role of inflammation and cytokines in brain injury. 888 Jul 34

We have investigated the cerebral cortex of Alzheimer's disease in which small infarcts are found on postmortem neuropathological examination. In areas that have been subjected to recent ischemia, immunohistochemical staining for amyloid beta-protein (A beta) is much less intense than in the non-ischemic surround. However, the infiltrating brain macrophages contain granules immunopositive for C-terminal fragments of A beta. The immunohistochemical profile indicates that A beta in these granules lacks epitopes in the N-terminal fragments. These data suggest that appropriately stimulated macrophages can phagocytose A beta deposits and that digestion of the N-terminal region is an early consequence of this phagocytosis.
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PMID:The amino-terminally truncated forms of amyloid beta-protein in brain macrophages in the ischemic lesions of Alzheimer's disease patients. 897 93

Calcium ion (Ca2+) plays a role in several important functions in the central nervous system such as production of action potentials, neurotransmitter release, or neuronal plasticity, etc. However, its excessive influx to neurons due to failure of the mechanisms implicated in the regulation of its intracellular concentration (Ca(2+)-channels, calcium binding proteins), leads to a cascade of events which causes cytotoxicity and neuronal death. Ca2+ mediated toxicity has been implicated in the pathogenesis of neurodegenerative diseases (Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, Huntington's), brain ischemia, epilepsy, cranial trauma, and AIDS-dementia complex. In this article we review the current status of this topic.
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PMID:[Calcium, neuronal death and neurological disease]. 898 15

A growing amount of data using light and electron microscopy, immunocytochemistry, uptake of brain markers and metabolic studies suggest that the pathogenesis of Alzheimer's disease may be due to impaired vascular delivery of nutrients to the brain. The bulk of this evidence indicates that cerebral capillary transport of glucose, oxygen and other vital nutrients is dysfunctional in Alzheimer brains due to abnormal hemodynamic flow patterns caused by structural deformities of the capillaries. Clinical disorders which can worsen cerebral blood flow, such as head injury, coronary artery disease, cerebrovascular ischemia or the presence of apolipoprotein E4 allele will increase the risk of Alzheimer's dementia. By contrast, activities that increase cerebral blood flow during aging such as complex thinking patterns or the use of drugs to reduce vascular resistance, such as aspirin or NSAIDs, will reduce the risk or improve the status of Alzheimer's disease. The production of neuritic plaques and neurofibrillary tangles may develop from the hypometabolic abnormalities caused by the impaired cerebromicrovasculature in Alzheimer brains. Such metabolic and cerebral blood flow changes are considerably less significant in age-matched control subjects. The major physiological, pathological and cognitive changes reported for Alzheimer's disease appear to have a common denominator which is reflected by the physically distorted cerebromicrovessels and their inability to optimally deliver nutrients to the brain, a condition which ultimately disturbs neurono-glial homeostasis.
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PMID:Cerebromicrovascular pathology in Alzheimer's disease compared to normal aging. 899 28

The major neurodegenerative disorders include Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis. Although their etiology and pathogenesis are unknown, numerous recent studies suggest that oxygen-derived free radicals play an important role. Furthermore, these reactive oxygen species are probably important in brain ischemia and reperfusion, Down's syndrome, and the mitochondrial encephalopathies. In this review, evidence for oxygen-derived free radicals in the pathogenesis of these disorders is discussed.
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PMID:Reactive oxygen species and the neurodegenerative disorders. 899 53

The laboratory examination of cerebrospinal fluid (CSF) continues to play an important role in the clinical diagnosis and treatment of various disorders of the central nervous system (CNS). The major conditions currently include, as they have in the past, infectious diseases, neoplastic processes, multiple sclerosis, other demyelinating disorders, and intracerebral hemorrhage. Recent publications suggest a variety of new laboratory tests that may be useful in the evaluation of patients with both primary and metastatic malignancies, Alzheimer's disease, Creutzfeld-Jacob disease, global ischemia, various psychiatric disorders, CSF otorrhea and rhinorrhea, and in the differential diagnosis of cortical vs lacunar stroke, among others. Examples of these recent developments and their possible clinical usefulness are discussed.
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PMID:Advances in the analysis of cerebrospinal fluid. 909 8

Phospholipases A2 are a heterogeneous class of enzymes that hydrolyse fatty acids from the sn-2 2 position of membrane phospholipids. Prolonged stimulation of phospholipase A2 may damage membrane integrity, not only because of the loss of essential phospholipid from the lipid bilayer but also as a result of an uncontrollable Ca2+ influx. The increased levels of intracellular Ca2+ may be responsible for enhanced lipolysis, proteolysis and DNA fragmentation. This process along with the accumulation of lipid peroxidation products may be associated with neurodegeneration in acute neural trauma (ischemia, head and spinal cord injuries) and neurodegenerative diseases (Alzheimer's disease).
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PMID:Involvement of phospholipase A2 in neurodegeneration. 915 92

Neurodegeneration associated with neurological disorders such as epilepsy, Huntington's Chorea, Alzheimer's disease, and olivoponto cerebellar atrophy or with energy failure such as ischemia, hypoxia, and hypoglycemia proceeds subsequent to overexposure of neurons to excitatory amino acids of which glutamate and aspartate may be quantitatively the most important. The toxic action of glutamate and aspartate is mediated through activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA subtypes. Antagonists for these receptors can act as neuroprotectants both in in vitro model systems (e.g., cultured neurons) and in vivo. Activation of receptors leads to an increase in the intracellular Ca++ concentration and also to an increase in other second messengers such as cGMP. Thus, Ca++ channel antagonists may have neuroprotective action under certain conditions.
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PMID:Role of Ca+2 and other second messengers in excitatory amino acid receptor mediated neurodegeneration: clinical perspectives. 918 41

L-Glutamic acid is a major excitatory neurotransmitter in the mammalian central nervous system. The termination of the glutamatergic transmission and the clearance of the excessive, neurotoxic concentrations of glutamate is ensured by a high affinity glutamate uptake system. Four homologous types of Na/K-dependent high affinity glutamate transporters, glutamate/aspartate transporter, glutamate transporter 1, excitatory amino acid carrier 1, and excitatory amino acid transporter 4, have recently been cloned and were assigned to a separate gene family, together with two neutral amino acid carriers, alanine/serine/cysteine transporter 1/serine/alanine/threonine transporter and adipocyte amino acid transporter. The genomic organization of these transporters is still under investigation. Very little is known about the nature of the factors and molecular mechanisms that regulate developmental, regional, and cell type-specific expression of the glutamate transporters and their aberrant functioning in neurodegenerative diseases (e.g., amyotrophic lateral sclerosis and Alzheimer's disease). Some experimental conditions (e.g., ischemia, corticostriatal lesions, hyperosmolarity, culturing conditions) and several naturally occurring and synthetic compounds (e.g., glutamate receptor agonists, dopamine, alpha1- and beta-adrenergic agonists, cAMP, phorbol esters, arachidonic acid, nitric oxide, oxygen free radicals, amyloid beta-peptide, tumor necrosis factor-alpha, glucocorticosteroids, unidentified neuronal factors) affect the molecular expression and activity of glutamate transporters. Further elucidation of the molecular events that link epigenetic signals with transcriptional and post-transcriptional mechanisms (e.g., alternative splicing, translation and post-translational modifications) is crucial for the development of selective pharmacological tools and strategies interfering with the expression of the individual glutamate transporters.
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PMID:High affinity glutamate transporters: regulation of expression and activity. 922 6


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