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  • 1
    Electronic Resource
    Electronic Resource
    ATP-Evoked Calcium Flux, Protein Phosphorylation, and Stellation in Astrocytes (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 603 (1990), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1990.tb37709.x
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  • 2
    Electronic Resource
    Electronic Resource
    Destabilization of Glial Fibrillary Acidic Protein mRNA in Astrocytes by Ammonia and Protection by Extracellular ATP (1994)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 63 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The expression of the astrocyte-specific intermediate filament protein, glial fibrillary acidic protein (GFAP), is decreased in hepatic encephalopathy and increased in numerous neurological conditions including brain injury. However, little is known about the molecular mechanisms that regulate GFAP expression. Here it is reported that treatment of cultured astrocytes with ammonium chloride reduces GFAP mRNA by up to 85% without inhibiting total RNA synthesis. The effect of NH4Cl was time and dose dependent. The reduction in GFAP mRNA was detected 3 h after initiation of ammonia treatment with a maximum effect observed at 24 h. Significant decreases in GFAP mRNA were observed at 2, 5, and 10 mM NH4Cl. Concurrent treatment with extracellular ATP prevented the loss of GFAP mRNA, possibly by activation of purinergic receptors. In addition, removal of ammonium chloride restored GFAP mRNA to normal levels. Nuclear runoff experiments indicated that NH4Cl did not inhibit GFAP mRNA transcription. Studies using α-amanitin, an inhibitor of RNA polymerase II, showed that NH4Cl decreased the stability of GFAP mRNA by ∼50%. This destabilization of GFAP mRNA may be an important factor in the pathogenesis of hepatic encephalopathy. Because increased GFAP is an important component of reactive gliosis, understanding the mechanisms that destabilize GFAP mRNA may facilitate strategies to minimize the gliosis associated with brain injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.63062021.x
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  • 3
    Electronic Resource
    Electronic Resource
    Role of Phosphoinositide Hydrolysis in Astrocyte Volume Regulation (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 61 (1993), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Astrocytes exposed to hypoosmotic stress swell and subsequently reduce their size to almost their original volume, a phenomenon called regulatory volume decrease (RVD). We found that during hypoosmotic swelling there was a twofold increase in phosphatidylinositol (PI) hydrolysis. This increase was inhibited by the phosphdipase C inhibitor, U-73122 (10 μM). Inhibition of PI hydrolysis resulted in blockage of RVD. We also examined whether agents that stimulate PI hydrolysis would enhance RVD. These agents significantly accelerated RVD. The rank order of potency was endothelin (20 nM) ≥ norepinephrine (100 μM) 〉 endothelin-3 (7 nM) 〉 thrombin (1 U/ml) ≥ ATP (500 μM) 〉 bradykinin (20 μM) ≥ carbachol (500 μM), as indicated by RVD rate constants. The extent of PI hydrolysis induced by these agents at the beginning of RVD exhibited a logarithmic relationship with the magnitude of RVD enhancement. Also, there was a linear relationship between the rate of PI hydrolysis and RVD rate constants. Our results suggest that stimulated PI hydrolysis is involved in the regulation of cell volume in astrocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1993.tb13646.x
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  • 4
    Electronic Resource
    Electronic Resource
    Protein Kinase C in Primary Astrocyte Cultures: Cytoplasmic Localization and Translocation by a Phorbol Ester (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 50 (1988), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in supernatant and paniculate fractions of primary cultures of rat astrocytes and its translocation by a phorbol ester were studied. We observed that 91% of protein kinase C activity in astrocytes was in the supernatant fraction, as measured by lysine-rich histone phosphorylation assay. Attempts to uncover latent activity in the particulate fraction were unsuccessful. Approximately 75% of the supernatant protein kinase C activity could be translocated to the particulate fraction by prior treatment (30–60 min) of the cultures with 100 nM 12-O-tetradecanoyl-phorbol 13-acetate (TPA), but not with 4α-phorbol, an inactive phorbol ester. Investigation of endogenous substrates for protein kinase C showed that TPA treatment brought about an increase in phosphor ylation in membrane proteins and a decrease in phosphorylation of supernatant proteins. These findings indicate that the distribution of protein kinase C in astrocytes differs substantially from that in whole brain tissue, where approximately two-thirds of the protein kinase C activity is associated with the particulate fraction. Because protein kinase C is concentrated in the cytosol of astrocytes and most of this activity can be translocated to membranes, astrocytes may be particularly well-suited to respond to signals that activate phosphoinositide-linked receptors in brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1988.tb10590.x
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  • 5
    Electronic Resource
    Electronic Resource
    Synergistic Activation of DNA Synthesis in Astrocytes by Fibroblast Growth Factors and Extracellular ATP (1994)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 63 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of extracellular ATP and polypeptide growth factors on DNA synthesis in primary cultures of rat astrocytes have been examined. It was found that ATP acts synergistically with either acidic or basic fibroblast growth factor to stimulate DNA synthesis. The specificity of this effect was demonstrated by the inability of ATP to potentiate DNA synthesis induced by platelet-derived growth factor or epidermal growth factor. ATP appears to act via P2 purinergic receptors, because (a) it was more effective than adenosine and (b) the synergistic effect was observed with the hydrolysis-resistant P2 agonists, ADPβS and ATPγS. The evidence suggests that extracellular ATP may be an important factor in regulating the extent of gliosis and, as such, may be involved in mechanisms of neural injury and repair.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.63020490.x
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  • 6
    Electronic Resource
    Electronic Resource
    Effects on free radical generation by ligands of the peripheral benzodiazepine receptor in cultured neural cells (2002)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 83 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of peripheral benzodiazepine receptor (PBR) ligands on free radical production was investigated in primary cultures of rat brain astrocytes and neurons as well as in BV-2 microglial cell lines using the fluorescent dye dichlorofluorescein-diacetate. Free radical production was measured at 2, 30, 60 and 120 min of treatment with the PBR ligands 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (Ro5-4864) and protoporphyrin IX (PpIX) (all at 10 nm). In astrocytes, all ligands showed a significant increase in free radical production at 2 min. The increase was short-lived with PK11195, whereas with Ro5-4864 it persisted for at least 2 h. PpIX caused an increase at 2 and 30 min, but not at 2 h. Similar results were observed in microglial cells. In neurons, PK11195 and PpIX showed an increase in free radical production only at 2 min; Ro5-4864 had no effect. The central-type benzodiazepine receptor ligand, clonazepam, was ineffective in eliciting free radical production in all cell types. As the PBR may be a component of the mitochondrial permeability transition (MPT) pore, and free radical production may occur following induction of the MPT, we further investigated whether cyclosporin A (CsA), an inhibitor of the MPT, could prevent free radical formation by PBR ligands. CsA (1 µm) completely blocked free radical production following treatment with PK11195 and Ro5-4864 in all cell types. CsA was also effective in blocking free radical production in astrocytes following PpIX treatment, but it failed to do so in neurons and microglia. Our results indicate that exposure of neural cells to PBR ligands generates free radicals, and that the MPT may be involved in this process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2002.01261.x
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  • 7
    Electronic Resource
    Electronic Resource
    Extracellular ATP induces stellation and increases glial fibrillary acidic protein content and DNA synthesis in primary astrocyte cultures (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 8-13 
    Details
    ISSN: 1432-0533
    Keywords: Key words: Astrocytes – Gliosis – Extracellular ATP – Glial fibrillary acidic protein – Stellation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A number of factors appear to be involved in the proliferative and hypertrophic processes which characterize reactive astrocytosis. We have investigated the possibility that ATP, an agent that is released by injured cells following tissue destruction, may be one such factor. For this purpose, we utilized primary cultures of astrocytes derived from cerebral cortices of neonatal rats to study the effect of extracellular ATP on properties associated with astrogliosis. Light microscopic studies disclosed marked stellation of astrocytes after 30 – 60 min of exposure to 100 µM−1 mM ATP. In addition, the content of the astrocyte-specific intermediate filament, glial fibrillary acidic protein (GFAP), was increased 35 – 40% following 60-min exposure to ATP; this effect persisted for 1 – 3 days exposure to 100 µM ATP. [3H]Thymidine incorporation increased progressively from 1 – 3 days; a 3.6-fold increase in DNA synthesis was observed following 3 days of exposure to 1 mM ATP, suggesting stimulation of cellular proliferation. These findings show that high micromolar to low millimolar concentrations of extracellular ATP reproduce several features associated with reactive gliosis and suggest that extracellular ATP may be involved in the activation of astrocytes following CNS injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00386249
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  • 8
    Electronic Resource
    Electronic Resource
    Acute traumatic central cord syndrome: MRI-pathological correlations (1992)
    Springer
    Neuroradiology 34 (1992), S. 85-94 
    Details
    ISSN: 1432-1920
    Keywords: Acute traumatic central cord syndrome ; Magnetic resonance imaging ; Pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The acute traumatic central cord syndrome (ATCCS) is commonly stated to result from an injury which affects primarily the center of the spinal cord and is frequently hemorrhagic. To test the validity of this widely disseminated hypothesis, the magnetic resonance images [MRI] of 11 consecutive cases of ATCCS caused by closed injury to the spine were analyzed and correlated with the gross pathological and histological features of 3 cervical spinal cords obtained at post mortem from patients with ATCCS, including 2 of patients studied by MRI. The MRI studies were performed acutely (18 h to 2 days after injury) in 7 patients and subacutely (3–10 days after injury) in 4. Ten of the 11 patients had pre-existing spondylosis and/or canal stenosis. The 11th suffered a cervical fracture. All patients exhibited hyperintense signal within the parenchyma of the cervical spinal cord on gradient echo MRI. None showed MRI features characteristic of hemorrhage on T1-weighted spin echo or T2*-weighed gradient echo studies. Gross and histological examination of the necropsy specimens showed no evidence of blood or blood products within the cord parenchyma: the primary finding was diffuse disruption of axons, especially within the lateral columns of the cervical cord in the region occupied by the corticospinal tracts. The central gray matter was intact. In patients with ATCCS, the predominant loss of motor function in thedistal muscles of the upper limbs may reflect the importance of the corticospinal tract for hand and finger function in the primate. In this study, the MRI and pathological observations indicate that ATCCS is predominantly a white matter injury and that intramedullary hemorrhage is not a necessary feature of the syndrome; indeed, it is probably an uncommon event in ATCCS. We suggest that the most common mechanism of injury in ATCCS may be direct compression of the cervical spinal cord by buckling of the ligamenta flava into an already narrowed cervical spinal canal; this would explain the predominance of axonal injury in the white matter of the lateral columns.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00588148
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  • 9
    Electronic Resource
    Electronic Resource
    Extracellular ATP induces stellation and increases glial fibrillary acidic protein content and DNA synthesis in primary astrocyte cultures (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 8-13 
    Details
    ISSN: 1432-0533
    Keywords: Astrocytes ; Gliosis ; Extracellular ATP Glial fibrillary acidic protein ; Stellation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of factors appear to be involved in the proliferative and hypertrophic processes which characterize reactive astrocytosis. We have investigated the possibility that ATP, an agent that is released by injured cells following tissue destruction, may be one such factor. For this purpose, we utilized primary cultures of astrocytes derived from cerebral cortices of neonatal rats to study the effect of extracellular ATP on properties associated with astrògliosis. Light microscopic studies disclosed marked stellation of astrocytes after 30–60 min of exposure to 100 μM-1 mM ATP. In addition, the content of the astrocyte-specific intermediate filament, glial fibrillary acidic protein (GFAP), was increased 35–40% following 60-min exposure to ATP; this effect persisted for 1–3 days of exposure to 100 μM ATP. [3H]Thymidine incorportion increased progressively from 1–3 days; a 3.6-fold increase in DNA synthesis was observed following 3 days of exposure to 1 mM ATP, suggesting stimulation of cellular proliferation. These findings show that high micromolar to low millimolar concentrations of extracellular ATP reproduce several features associated with reactive gliosis and suggest that extracellular ATP may be involved in the activation of astrocytes following CNS injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00386249
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    Paper (German National Licenses)
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  • 10
    Electronic Resource
    Electronic Resource
    Ammonia-induced astrocyte swelling in primary culture (1991)
    Springer
    Neurochemical research 16 (1991), S. 833-836 
    Details
    ISSN: 1573-6903
    Keywords: Ammonia ; brain edema ; hepatic encephalopathy ; hepatic failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of ammonia on water space of astrocytes in culture was determined as a means of studying the neurotoxicity of ammonia in fulminant hepatic failure (FHF). Treatment of primary astrocyte cultures obtained from neonatal rat cortices with 10 mM NH4Cl for 4 days resulted in a 29% increase in astrocytic water space, as measured by an isotopic method utilizing 3-O-methyl-[3H]-glucose. this effect was time- and dose-dependent. The ammonia-induced swelling was reversible as the water space in cultures treated with 10 mH NH4Cl for 3 days, and then returned to normal culture media for 1 day, was similar to control cultures. These findings suggest that elevated levels of ammonia lead to astrocyte swelling and may contribute to the brain edema in FHF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00965694
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