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  1. Book: Glial cell receptors

    Kimelberg, Harold K.

    1988  

    Author's details ed. Harold K. Kimelberg
    Keywords Neuroglia / physiology ; Receptors, Neurotransmitter / physiology ; Glia ; Neurotransmitter-Rezeptor
    Subject Neurorezeptor ; Neuroglia
    Size XIII, 274 S. : Ill., graph. Darst.
    Edition 1. [Dr.]
    Publisher Raven Pr
    Publishing place New York
    Publishing country United States
    Document type Book
    HBZ-ID HT003156126
    ISBN 0-88167-401-X ; 978-0-88167-401-9
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    1988 A 3428 order for loan Magazin

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  2. Article ; Online: Functions of mature mammalian astrocytes: a current view.

    Kimelberg, Harold K

    The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

    2010  Volume 16, Issue 1, Page(s) 79–106

    Abstract: ... such as control of increases in extracellular K(+), uptake of excitatory amino acids, and alterations ...

    Abstract Before the roles of normal, mature astrocytes in the mammalian CNS can be discussed, we first need to define these cells. A definition proposed here is that such a class is best defined as consisting of the protoplasmic and fibrous astrocytes of the gray and white matter, respectively, the Bergmann glia of the molecular layer of the cerebellum, and the Muller cells of the retina. It is concluded that the established properties and functions of these mature astrocytes are essential support for neuronal activity, in the sense of Claude Bernard's principle of maintaining "la fixité du milieu intérieur." This milieu would be the extracellular space common to astrocytes and neurons. More specialized roles, such as the recently described "light guides" for retinal Muller cells can also be viewed as support and facilitation. The ECS is also, of course, common to all other neural cells, but here, I limit the discussion to perturbations of the ECS caused only by neuronal activities and the resolution of these perturbations by astrocytes, such as control of increases in extracellular K(+), uptake of excitatory amino acids, and alterations in blood vessel diameter and therefore blood flow. It is also proposed how this fits into the current morphological picture for the protoplasmic astrocytes as having small cell bodies with up to 100,000 process endings that occupy separate territories on which the processes of neighboring astrocytes scarcely intrude.
    MeSH term(s) Animals ; Astrocytes/physiology ; Brain/physiology ; Humans ; Mammals/physiology ; Models, Neurological
    Language English
    Publishing date 2010-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1233753-5
    ISSN 1089-4098 ; 1073-8584
    ISSN (online) 1089-4098
    ISSN 1073-8584
    DOI 10.1177/1073858409342593
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  3. Article: Volume activated anion channel and astrocytic cellular edema in traumatic brain injury and stroke.

    Kimelberg, Harold K

    Advances in experimental medicine and biology

    2008  Volume 559, Page(s) 157–167

    MeSH term(s) Animals ; Astrocytes/drug effects ; Astrocytes/pathology ; Brain/ultrastructure ; Brain Injuries/complications ; Cats ; Cell Size/drug effects ; Edema/pathology ; Fluorenes/pharmacology ; Glutamic Acid/metabolism ; Ion Channel Gating/drug effects ; Ion Channels/metabolism ; Microdialysis ; Neuroprotective Agents/pharmacology ; Rats ; Stroke/complications ; Survival Analysis ; Tamoxifen/pharmacology
    Chemical Substances Fluorenes ; Ion Channels ; Neuroprotective Agents ; Tamoxifen (094ZI81Y45) ; Glutamic Acid (3KX376GY7L) ; L 644711 (SC0Y88002K)
    Language English
    Publishing date 2008-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/0-387-23752-6_15
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  4. Article ; Online: Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal.

    Kimelberg, Harold K

    Neuron glia biology

    2008  Volume 3, Issue 3, Page(s) 181–189

    Abstract: It has been proposed that astrocytes should no longer be viewed purely as support cells for neurons, such as providing a constant environment and metabolic substrates, but that they should also be viewed as being involved in affecting synaptic activity ... ...

    Abstract It has been proposed that astrocytes should no longer be viewed purely as support cells for neurons, such as providing a constant environment and metabolic substrates, but that they should also be viewed as being involved in affecting synaptic activity in an active way and, therefore, an integral part of the information-processing properties of the brain. This essay discusses the possible differences between a support and an instructive role, and concludes that any distinction has to be blurred. In view of this, and a brief overview of the nature of the data, the new evidence seems insufficient to conclude that the physiological roles of mature astrocytes go beyond a general support role. I propose a model of mature protoplasmic astrocyte function that is drawn from the most recent data on their structure, the domain concept and their syncytial characteristics, of an independent rather than integrative functioning of the ends of each process where the activities that affect synaptic activity and blood vessel diameter will be concentrated.
    Language English
    Publishing date 2008-05-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2143089-5
    ISSN 1741-0533 ; 1740-925X ; 1741-0533
    ISSN (online) 1741-0533
    ISSN 1740-925X ; 1741-0533
    DOI 10.1017/S1740925X08000094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Tamoxifen as a powerful neuroprotectant in experimental stroke and implications for human stroke therapy.

    Kimelberg, Harold K

    Recent patents on CNS drug discovery

    2008  Volume 3, Issue 2, Page(s) 104–108

    Abstract: Several recent studies from the author's laboratory have shown that tamoxifen, at higher concentrations than used for breast cancer and given i.v., can substantially prevent tissue infarct and behavioral deficits in reversible and permanent rat focal ... ...

    Abstract Several recent studies from the author's laboratory have shown that tamoxifen, at higher concentrations than used for breast cancer and given i.v., can substantially prevent tissue infarct and behavioral deficits in reversible and permanent rat focal stroke models for up to at least 14 days after initiation of ischemia. Longer times and purely i.p. or oral administration have not yet been tried. Its marked effectiveness may be because it has several neuroprotective modes of action including free radical scavenging and, being highly lipid soluble, readily crosses the blood-brain barrier. Plus, it has a three hour therapeutic window. Thus it meets many of the STAIR criteria and should be a promising candidate for clinical use. However, a number of its positive effects were exhibited by the free radical trapping agent NXY-058, which also functions as a free radical scavenger. In two recently completed clinical trials (SAINT 1 and 2) NXY-058 had marginal positive effects and did not meet treatment criteria, respectively. Differences that may make tamoxifen still desirable and the problem of predicting clinical efficacy from successful animal studies are discussed.
    MeSH term(s) Animals ; Disease Models, Animal ; Humans ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/therapeutic use ; Stroke/prevention & control ; Tamoxifen/chemistry ; Tamoxifen/therapeutic use
    Chemical Substances Neuroprotective Agents ; Tamoxifen (094ZI81Y45)
    Language English
    Publishing date 2008-05-13
    Publishing country United Arab Emirates
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2253602-4
    ISSN 2212-3954 ; 1574-8898
    ISSN (online) 2212-3954
    ISSN 1574-8898
    DOI 10.2174/157488908784534603
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  6. Article: Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy.

    Kimelberg, Harold K

    Glia

    2005  Volume 50, Issue 4, Page(s) 389–397

    Abstract: In this viewpoint article, I summarize data showing that the astrocytic swelling that occurs early after the acute CNS pathologies ischemia and traumatic brain injury is damaging. We have proposed that one reason may be the release of excitatory amino ... ...

    Abstract In this viewpoint article, I summarize data showing that the astrocytic swelling that occurs early after the acute CNS pathologies ischemia and traumatic brain injury is damaging. We have proposed that one reason may be the release of excitatory amino acids (EAA) via volume-activated anion channels (VRACs) that are activated by such swelling. This release could be a target for therapy, which could involve blocking the astrocytic swelling or the release mechanisms. The transport mechanisms likely causing the early astrocytic swelling are therefore summarized. In terms of targeting the release mechanisms, we have found a potent inhibitor of VRACs, tamoxifen, to be strongly neuroprotective in focal ischemia with a therapeutic window of 3 h after initiation of the ischemia. The question, however, of whether neuroprotection by tamoxifen can be solely attributed to VRAC inhibition in astrocytes has yet to be resolved.
    MeSH term(s) Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Astrocytes/pathology ; Brain Injuries/drug therapy ; Brain Injuries/metabolism ; Brain Injuries/pathology ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Cell Size/drug effects ; Drug Delivery Systems/methods ; Humans
    Language English
    Publishing date 2005-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.20174
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  7. Article: The role of hypotheses in current research, illustrated by hypotheses on the possible role of astrocytes in energy metabolism and cerebral blood flow: from Newton to now.

    Kimelberg, Harold K

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2004  Volume 24, Issue 11, Page(s) 1235–1239

    MeSH term(s) Animals ; Astrocytes/metabolism ; Biomedical Research ; Brain/blood supply ; Brain/cytology ; Brain/metabolism ; Cerebrovascular Circulation/physiology ; Energy Metabolism ; Humans ; Models, Biological ; Neurons/metabolism
    Language English
    Publishing date 2004-11
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1097/01.WCB.0000138668.10058.8C
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  8. Article: The problem of astrocyte identity.

    Kimelberg, Harold K

    Neurochemistry international

    2004  Volume 45, Issue 2-3, Page(s) 191–202

    Abstract: Astrocytes were the original neuroglia of Ramón y Cajal but after 100 years there is no satisfactory definition of what should comprise this class of cells. This essay takes a historical and philosophical approach to the question of astrocytic identity. ... ...

    Abstract Astrocytes were the original neuroglia of Ramón y Cajal but after 100 years there is no satisfactory definition of what should comprise this class of cells. This essay takes a historical and philosophical approach to the question of astrocytic identity. The classic approach of identification by morphology and location are too limited to determine new members of the astrocyte population. I also critically evaluate the use of protein markers measured by immunoreactivity, as well as the newer technique of marking living cells by using promoters for these same proteins to drive reporter genes. These two latter approaches have yielded an expanded population of astrocytes with diverse functions, but also mark cells that traditionally would not be defined as astrocytes. Thus we need a combination of measures to define an astrocyte but it is not clear what this combination should be. The molecular approach, especially promoter driven fluorescent reporter genes, does have the advantage of pre marking living astrocytes for electrophysiological or imaging recordings. However, lack of sufficient understanding of the behavior of the inserted constructs has led to unclear results. This approach will no doubt be perfected with time but at present an acceptable, practical definition of what constitutes the class of astrocytes remains elusive.
    MeSH term(s) Animals ; Astrocytes/cytology ; Astrocytes/physiology ; Biomarkers ; Glial Fibrillary Acidic Protein/analysis ; Humans ; Neuroglia/classification ; Neuroglia/physiology ; Stem Cells/cytology ; Stem Cells/physiology
    Chemical Substances Biomarkers ; Glial Fibrillary Acidic Protein
    Language English
    Publishing date 2004-07
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/j.neuint.2003.08.015
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  9. Article: Increased release of excitatory amino acids by the actions of ATP and peroxynitrite on volume-regulated anion channels (VRACs) in astrocytes.

    Kimelberg, Harold K

    Neurochemistry international

    2004  Volume 45, Issue 4, Page(s) 511–519

    Abstract: ... swelling by exposure to high K+ medium) leads to release of the excitatory amino acids (EAAs) glutamate and ...

    Abstract Rapid swelling of astrocytes in primary culture by exposure to hyposmotic medium (or slower swelling by exposure to high K+ medium) leads to release of the excitatory amino acids (EAAs) glutamate and aspartate. One question that arises is whether these phenomena are only relevant to pathological states such as ischemia and trauma where marked astrocytic swelling occurs or whether much smaller astrocytic volume changes, that might be encountered under physiological states, will cause such release. We have recently found that extracellular ATP strongly potentiated volume-regulated anion channels (VRACs)-mediated-excitatory amino acid release in non-swollen and osmotically swollen primary astrocyte cultures. However, ATP does not seem to directly activate but instead positively modulates VRACs and we postulate that a minor fraction of these are active under isoosmotic conditions based on the finding that in hyperosmotic media the ATP-induced increase was inhibited. Agonist and inhibitor analysis suggests that the effect of ATP is mediated by several subtypes of metabotropic P2Y receptors. Thus, the concept of volume transmission may be extended to volume-mediated transmission, whereby moderate cell swelling causes release of neurotransmitter substances. The product of the superoxide oxygen radical and nitric oxide, peroxynitrite, formed under pathological conditions such as cerebral ischemia, also potentiated the release of D-[3H]aspartate from astrocyte cultures exposed to limited or marked swelling via intracellular signaling mechanisms involving tyrosine kinases (TKs). Thus, the enhancement of cell volume-dependent release of excitatory amino acids from astrocytes can be physiological or pathological and its magnitude depends on the degree of the cell volume increase.
    MeSH term(s) Adenosine Triphosphate/pharmacology ; Animals ; Animals, Newborn ; Astrocytes/drug effects ; Astrocytes/metabolism ; Astrocytes/ultrastructure ; Cell Size ; Cells, Cultured ; Culture Media ; Excitatory Amino Acids/metabolism ; Ion Channels/drug effects ; Ion Channels/metabolism ; Molsidomine/analogs & derivatives ; Molsidomine/pharmacology ; Nitric Oxide/physiology ; Nitric Oxide Donors/pharmacology ; Osmolar Concentration ; Peroxynitrous Acid/pharmacology ; Purinergic P2 Receptor Agonists ; Purinergic P2 Receptor Antagonists ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Culture Media ; Excitatory Amino Acids ; Ion Channels ; Nitric Oxide Donors ; Purinergic P2 Receptor Agonists ; Purinergic P2 Receptor Antagonists ; Peroxynitrous Acid (14691-52-2) ; Nitric Oxide (31C4KY9ESH) ; linsidomine (5O5U71P6VQ) ; Adenosine Triphosphate (8L70Q75FXE) ; Molsidomine (D46583G77X)
    Language English
    Publishing date 2004-09
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/j.neuint.2003.11.002
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  10. Article ; Online: Functions of astrocytes and their potential as therapeutic targets.

    Kimelberg, Harold K / Nedergaard, Maiken

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

    2010  Volume 7, Issue 4, Page(s) 338–353

    Abstract: Astrocytes are often referred to, and historically have been regarded as, support cells of the mammalian CNS. Work over the last decade suggests otherwise-that astrocytes may in fact play a more active role in higher neural processing than previously ... ...

    Abstract Astrocytes are often referred to, and historically have been regarded as, support cells of the mammalian CNS. Work over the last decade suggests otherwise-that astrocytes may in fact play a more active role in higher neural processing than previously recognized. Because astrocytes can potentially serve as novel therapeutic targets, it is critical to understand how astrocytes execute their diverse supportive tasks while maintaining neuronal health. To that end, this review focuses on the supportive roles of astrocytes, a line of study relevant to essentially all acute and chronic neurological diseases, and critically re-evaluates our concepts of the functional properties of astrocytes and relates these functions and properties to the intricate morphology of these cells.
    MeSH term(s) Animals ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Aquaporin 4/metabolism ; Astrocytes/pathology ; Astrocytes/physiology ; Central Nervous System Diseases/pathology ; Central Nervous System Diseases/therapy ; Complex Mixtures/metabolism ; Humans ; Hydrogen/metabolism ; Models, Biological ; Potassium/metabolism ; Regional Blood Flow/physiology ; Water/metabolism ; gamma-Aminobutyric Acid/metabolism
    Chemical Substances Antioxidants ; Aquaporin 4 ; Complex Mixtures ; Water (059QF0KO0R) ; glutamevit (108911-02-0) ; gamma-Aminobutyric Acid (56-12-2) ; Hydrogen (7YNJ3PO35Z) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2010-09-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2316693-9
    ISSN 1878-7479 ; 1933-7213
    ISSN (online) 1878-7479
    ISSN 1933-7213
    DOI 10.1016/j.nurt.2010.07.006
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