Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of vasogenic brain edema on amine neurotransmitter concentrations was studied in rats bearing transplanted glioma C6 brain tumors. In comparison with sham-operated and nonoperated controls, the tumor-implanted animals showed significant decreases in both dopamine (DA) and norepinephrine (NE) in the hypothalamus, cortex, and striatum. Treatment with dexamethasone (DEX) tended to restore these monoamines to the levels measured in sham-operated controls. In the nonoperated controls, DEX significantly increased NE but not DA. In tumor-bearing rats there was no increase in hypothalamic or striatal water content, and DEX had no effect on the water content of these structures. However, there was a significant increase in the cortical water content, which was reduced by DEX to the control levels. The water content within the tumor was also significantly decreased by DEX. In the nonoperated controls, there was no difference in water content between DEX-treated and nontreated animals. These findings suggest that tumor-induced brain edema reduces noradrenergic and dopaminergic activities. DEX administration resulted in normalization of the water content in edematous regions and of the DA and NE concentrations, and brought about marked symptomatic improvement.
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PMID:Neurotransmitter amines in brain edema of a rat glioma model. 247 22

A vascular permeability factor (VPF) derived from serum-free conditioned medium of cultured human malignant gliomas (HG-VPF) has been described previously. The rapid kinetics of HG-VPF activity in an in vivo assay of vascular permeability suggests a direct action upon the vascular endothelial cell. To determine whether HG-VPF was capable of inducing a physiologically significant alteration in isolated endothelial cells, cytosolic calcium [Ca++]i was measured in vitro in these cells before and after their exposure to media containing this substance. This was accomplished by preloading cultured endothelial cells with a fluorescent intracellular Ca++ probe fura-2/AM. It was found that HG-VPF induced a rapid and transient elevation of [Ca++]i in normal endothelial cells derived from human umbilical vein, bovine adrenal medulla, bovine pulmonary artery, and rat brain. This effect was inhibited by chelating extracellular calcium [Ca++]e with ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA), indicating that the HG-VPF-induced response resulted from the influx of extracellular calcium. The addition of cations that act as nonspecific calcium channel blockers (Li+, Co++, Mn++, La ) completely inhibited VPF activity, further supporting the role of [Ca++]e influx. The HG-VPF activity was not, however, blocked by verapamil, a calcium antagonist that appears to be specific for voltage-gated calcium channels. Furthermore, exposure of endothelial cells to 120 mM [K+]e did not result in a calcium transient. Coincubation of endothelial cells with dexamethasone inhibited HG-VPF-induced rises in [Ca++]i, while having no effect upon cyclic nucleotide-induced changes in calcium. The present studies indicate that vascular extravasation induced by human glioma-derived VPF may be mediated by a direct action upon vascular endothelial cells. Furthermore, the observed dexamethasone-induced inhibition of this process suggests a specific cellular action for corticosteroids. This, together with previous observations that dexamethasone suppresses both the production of VPF by tumor cells in vitro and its permeability-inducing activity in vivo, may explain the efficacy of glucocorticoids in the treatment of neoplastic vasogenic brain edema. Finally, studies with a polycationic peptide (protamine) known to induce blood-brain barrier disruption in vivo revealed similar effects upon endothelial cytosolic calcium levels. As HG-VPF is a positively charged macromolecule, a common interaction between these substances and the negatively charged endothelial cell surface in the induction of permeability is suggested. Nonspecific cross-linking of charged groups of the endothelial glycocalyx and specific HG-VPF receptor binding are both valid mechanisms of HG-VPF-mediated calcium changes. Their potential relevance in the setting of microvascular permeability is discussed.
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PMID:Cytosolic calcium changes in endothelial cells induced by a protein product of human gliomas containing vascular permeability factor activity. 258 81

Nitrosourea-induced rat brain tumors are among the best investigated experimental systems for neuropathological, biochemical, diagnostic and therapeutic research in neurooncology. This review summarizes data concerning molecular biology, neuropathology, in vitro studies, transplantation models and antigen expression of experimental gliomas in inbred rat strains. Systemic application of nitroso-compounds, i.e., ENU and MNU, leads to the alkylation of DNA bases, which, due to a specific repair deficiency, persist in the nervous system remarkably longer than in other organs. The hypothesis is that alkylated bases cause base-mispairing and point mutations followed by uncontrolled expression of oncogenes and growth factor receptors, resulting in permanent cell proliferation. Thus, nitrosoureas are considered to be biological hazards, especially as potent endogenous and exogenous neurotoxins. Neuropathology and growth characteristics of these experimental tumors are comparable to human malignant gliomas. Similar to the human WHO grade III and IV tumors, they reveal cellular pleomorphism, elevated mitotic activity, proliferation of blood vessels, blood-brain barrier disturbances, necrosis and invasiveness. Nitrosourea-induced brain tumors have been used in investigations concerning glioma growth and regression, brain edema, glioma immunology, metabolism, regional biochemistry, and experimental therapy. The studies included conventional morphology, immunohistochemistry, -cytochemistry and -electronmicroscopy, morphometry, cell culture, hybridoma technology, tumor transplantation and regional imaging by autoradiography, bioluminescence, magnetic resonance and immunoscintigraphy.
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PMID:Chemical induction of brain tumors in rats by nitrosoureas: molecular biology and neuropathology. 269 75

One of the primary consequences of ischemia is tissue acidification due to anaerobic production of lactic acid. Upon reperfusion and recovery of pH, cytotoxic edema often ensues. Na+/H+ exchange, a mechanism involved in the regulation of intracellular pH (pHi), is activated by low intracellular pH, is dependent on extracellular Na+, and is inhibited by low extracellular pH (pH less than 6) or by amiloride. In this study we explore the role of Na+/H+ exchange in cell swelling following cytoplasmic acidification of C6 glioma cells. Postischemic intracellular acidification was simulated in vitro by exposure of cells in suspension to: (1) 20 or 140 mM lactic acid; or (2) 10 microM oligomycin. pHi was monitored fluorimetrically using the intracellularly trapped pH-sensitive dye bis(carboxyethyl)carboxyfluorescein. Cell volume was measured electronically with a Coulter Counter/Channelyzer. Both simulations of ischemia caused intracellular acidification followed by recovery. pHi recovery was mediated by Na+/H+ exchange, since it was amiloride-sensitive and Na+-dependent. This pHi reversal following lactic acid-induced acidification was also inhibited at pHo less than 6. Volume measurements showed that cells suspended in 140 mM Na-lactate/lactic acid swelled by 19% over 15 min. This swelling was Na+-dependent, and inhibited by amiloride and pHo less than 6. These results suggest that Na+/H+ exchange may be involved in cell swelling following cytoplasmic acidification, and thus may be involved in postischemic cytotoxic brain edema.
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PMID:Lactic acid-induced swelling in C6 glial cells via Na+/H+ exchange. 272 Apr 8

An in vivo model for correlative imaging studies of intracerebral glial tumors and peritumor brain edema has been developed. Adult male and female cats implanted with 1 x 10(6) or 5 x 10(5) 9L glioma cells had parietal tumors of 4 mm or greater in diameter and showed signs of increased intracranial pressure 13.7 +/- 1.9 days or 19.2 +/- 1.3 days after implantation. No immunosuppression was required and the success rate for tumor growth after implantation was 88%. Histologically, the tumor resembles a malignant astrocytoma. The tumor contained the highest water content (85.94%); peritumor white matter was more edematous (73.01%) than white matter in the contralateral hemisphere (69.04%), sham-operated (69.41%) and control brain (68.76%). There was no correlation between the size of the tumor and water content in tumor or white matter. Increased tissue albumin in peritumor white matter indicated blood-brain barrier dysfunction within the tumor and confirmed the vasogenic origin of the edema. Proton magnetic resonance imaging provided good spatial and contrast resolution with increased signal intensity in edematous white matter, decreasing with distance from the tumor. The large brain of this animal model allows the use of serial imaging and regional correlative biochemical measurements in a single animal. Other advantages of this model are its predictability and the short time required to produce tumors with marked peritumor edema.
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PMID:A feline model for experimental studies of peritumor brain edema. 322 Dec 63

In a prospective study the effect of dexamethasone treatment on tumor volume and contrast enhancement was evaluated by computed tomography (CT) in 15 patients with intracranial lesions. Histological diagnoses were confirmed in 13 patients who had undergone surgical intervention. A CT study of the head, with and without contrast medium, was performed prior to the dexamethasone treatment and at various intervals during the treatment for 8-19 days. The volume, attenuation, and contrast enhancement of the tumor were measured and related to the time after the start of the treatment. In six meningiomas there was no change in the volume and enhancement of the tumors. Out of four gliomas, there was an increase in volume of two tumors, whereas the other two cases showed a decrease in the tumor volume. In one glioma a distinct decrease in enhancement was observed. In three cases of metastasis a decrease in enhancement and tumor volume was noted. An acoustic neurinoma and an unverified lesion, considered radiologically to be a glioma, also showed a decrease in tumor volume and contrast enhancement. In tumors that responded to the treatment, a decrease both in volume of the tumor and peritumoral brain edema as well as a decrease in contrast enhancement of the tumor were observed.
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PMID:Effect of dexamethasone treatment on volume and contrast enhancement of intracranial neoplasms. 683 63

In these studies vasogenic brain edema has been induced by implantation of rat glioma cells RGI 2.2 into BD-IX rats while cytotoxic edema pas produced by permanent regional ischemia in the mongolian gerbil. In the gerbil sodium concentration was raised from 201 meq/kg d.w. (dry weight) [p/b (peak/background) = 0] to 269 meq/kg d.w. (p/b = 0.25; 2 hours) and 651 meq/kg d.w. [p/b = 0.71; 24 hours), whereas potassium concentration decreased from 373 meq/kg d.w. (p/b = 1.69) to 337 meq/kg d.w. (p/b = 1.65) and 152 meq/kg d.w. (p/b = 0.53). In the rat tumor sodium and potassium concentrations were 279 meq/kg d.w. (p/b = 0.44) and 510 meq/kg d.w. (p/b = 1.94). Non-tumorous tissue contained 237 meq/kg d.w. (p/b = 0) and 517 meq/kg d.w. (p/b = 1.98). In addition X-ray microanalysis could show that chlorine behaves like sodium, whereas the concentration of phosphorus and sulphur remains nearly constant. X-ray microanalysis in this case proved to be useful in the localization and quantification of different elements. The main disadvantage, however, is the reduced sensitivity for light elements, e.g. sodium, which cannot be determined in normal brain.
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PMID:Investigations on vasogenic and cytotoxic brain edema, comparing results from X-ray microanalysis and flame photometry. 708 98

CT scan of the one hundred and sixteen metastatic brain tumors in 50 patients was reviewed and compared to the previous reports. The most common primary organ was lung (43%) followed by breast (18%), colon (10%) and kidney (6%). Solitary nodule was found in 20 patients (40%). On plain CT scan, tumor nodules were demonstrated as slightly high density in 38 (33%), isodensity in 50 (43%) and slightly low density in 28 (24%). Majority of tumor nodules were present in the corticomedullary junction (82%). Brain edema seen as a peritumoral low density was extensive in comparison with the edema in the glioma of the similar size. On contrast CT scan, ring like enhancement was seen in 41 (35%). Intra-tumoral bleeding was shown in 2 metastatic nodules from choriocarcinoma and in one metastatic nodule from renal cell carcinoma. All 3 cases were proved by surgery or autopsy.
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PMID:[Computed tomography in brain metastases (author's transl)]. 710 9

Capillary permeability of rat brains bearing ethylnitrosourea induced rat glioma was measured with quantitative autoradiography. In the small tumors (less than 2mm in diameter), no changes in capillary permeability was noted. When tumors became larger and neovascularization of the tumor occurred, increase in capillary permeability was evident. This change was more prominent in the center of the tumor than in the periphery. In the large tumors, the capillary permeability was markedly increases, and the value was similar to that in the choroid plexus. This indicates that blood-brain barrier(BBB) completely disappeared in the large tumors. This BBB change may be the main cause of tumor induced brain edema. The data also provide the information about pharmacokinetics of water soluble drugs in the brain tumors.
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PMID:[Changes of blood-brain barrier in the ethylnitrosourea induced rat glioma (author's transl)]. 732 57

Recent studies using a rat model of pneumococcal meningitis have shown that nitric oxide synthase (NOS) inhibitors greatly attenuated microvascular changes and brain edema formation. The site of NO production during bacterial meningitis is unknown. In this study we tested whether primary astrocyte cultures from neonatal rat cortex can be induced to release NO upon stimulation with pneumococci. NO production was assessed by measuring nitrite in the cell culture supernatant using the Griess reaction. Stimulation with heat-killed unencapsulated pneumococci (HKP) increased nitrite concentrations in astrocyte culture supernatants in a dose-dependent fashion. Administration of N-nitro-L-arginine (L-NA), aminoguanidine, L-canavanine, cycloheximide, and dexamethasone prevented the increase in nitrite concentrations. Addition of L-arginine, but not of D-arginine, partially reversed the inhibitory effect of L-NA. Administration of SOD increased nitrite accumulation. Moreover, at 72 h after stimulation with heat-killed pneumococci (10(7) cfu/ml) astrocytes showed an inducible NOS-like immunoreactivity. Accumulation of nitrite was also observed when rat cerebellar neurons and microglia were stimulated with HKP, whereas there was only a slight increase of nitrite in media of rat C6 glioma cells, but no increase of nitrite when the human glioblastoma cell line LN-229 was stimulated with HKP. There was a stronger increase in nitrite levels when astrocytes from Lewis rats were used compared to that from Wistar rats. In conclusion, our study indicates that astrocytes, neurons and microglia are inducible for NO production upon stimulation with pneumococci.
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PMID:Production of nitrite by primary rat astrocytes in response to pneumococci. 764 48


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