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  1. Artikel ; Online: How inflammation modulates central nervous system vessel activation and provides targets for intervention--a personal perspective.

    Hallenbeck, John

    Annals of the New York Academy of Sciences

    2010  Band 1207, Seite(n) 1–7

    Abstract: I here describe a line of research that grew out of studies of spinal cord-damaging decompression sickness, focused on the blood-endothelial interface, that was influenced by the local Shwartzman phenomenon, addressed innate immune and inflammatory ... ...

    Abstract I here describe a line of research that grew out of studies of spinal cord-damaging decompression sickness, focused on the blood-endothelial interface, that was influenced by the local Shwartzman phenomenon, addressed innate immune and inflammatory mechanisms, and ultimately arrived at mucosal tolerance approaches to prevent stroke. Intranasal instillation of E-selectin is under development as a novel means of targeting immunomodulation to activating blood vessels within the vascular tree supplying the brain. The goal of this form of focused immunomodulation is to prevent recurrent strokes in patients that have previously suffered transient ischemic attacks or strokes.
    Mesh-Begriff(e) Animals ; Central Nervous System/blood supply ; Central Nervous System/physiopathology ; E-Selectin/administration & dosage ; Humans ; Inflammation/physiopathology ; Rats ; Shwartzman Phenomenon/physiopathology ; Stroke/prevention & control ; Tumor Necrosis Factor-alpha/physiology
    Chemische Substanzen E-Selectin ; Tumor Necrosis Factor-alpha
    Sprache Englisch
    Erscheinungsdatum 2010-10-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/j.1749-6632.2010.05785.x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Tracks of a non-main path traveler: 2011 Thomas Willis Lecture.

    Hallenbeck, John M

    Stroke

    2012  Band 43, Heft 2, Seite(n) 585–590

    Abstract: After an unconventional beginning in stroke research, I veered off the main path repeatedly to view problems from a different perspective. In this lecture summary, I would like to return to several points along the byways that led to research with some ... ...

    Abstract After an unconventional beginning in stroke research, I veered off the main path repeatedly to view problems from a different perspective. In this lecture summary, I would like to return to several points along the byways that led to research with some continuity.
    Mesh-Begriff(e) Animals ; Brain Ischemia/blood ; Brain Ischemia/pathology ; Capillaries/pathology ; Disease Models, Animal ; Endothelium, Vascular/pathology ; History, 20th Century ; History, 21st Century ; Humans ; Immunity/physiology ; Inflammation Mediators/physiology ; Internship and Residency ; Military Personnel ; Neurology/education ; Neurology/history ; Rats ; Stroke
    Chemische Substanzen Inflammation Mediators
    Sprache Englisch
    Erscheinungsdatum 2012-01-12
    Erscheinungsland United States
    Dokumenttyp Historical Article ; Lecture ; Research Support, N.I.H., Intramural
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.111.643668
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Introduction of a new journal.

    Hallenbeck, John M

    Translational stroke research

    2010  Band 1, Heft 1, Seite(n) 1

    Sprache Englisch
    Erscheinungsdatum 2010-03
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2541897-X
    ISSN 1868-601X ; 1868-4483
    ISSN (online) 1868-601X
    ISSN 1868-4483
    DOI 10.1007/s12975-010-0013-9
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  4. Artikel: Mucosal Administration of E-selectin Limits Disability in Models of Multiple Sclerosis.

    Quandt, Jacqueline A / Becquart, Pierre / Kamma, Emily / Hallenbeck, John

    Frontiers in molecular neuroscience

    2019  Band 12, Seite(n) 190

    Abstract: E-selectin plays an important role in mediating the rolling of leukocytes along and thus, the subsequent extravasation across activated endothelial cells comprising the microvasculature of the blood brain barrier (BBB). In multiple sclerosis (MS) and ... ...

    Abstract E-selectin plays an important role in mediating the rolling of leukocytes along and thus, the subsequent extravasation across activated endothelial cells comprising the microvasculature of the blood brain barrier (BBB). In multiple sclerosis (MS) and other inflammatory disorders of the central nervous system (CNS), the microvasculature is altered and immune cells infiltrate the brain and spinal cord contributing to damage, demyelination and ultimately disability. While mucosal administration is typically used to affect lymphocyte hyporesponsiveness or tolerance to suspect autoantigens, intranasal administration to E-selectin has previously been shown to protect against CNS inflammatory insults. We characterized the potential for mucosal administration of E-selectin to modulate CNS autoimmunity in the experimental autoimmune encephalomyelitis (EAE) model of MS. Intranasally administered E-selectin reduced swelling by as much as 50% in delayed-type hypersensitivity reactions compared to ovalbumin-tolerized controls. Intranasal E-selectin delivery prior to disease induction with myelin oligodendrocyte glycoprotein (MOG)
    Sprache Englisch
    Erscheinungsdatum 2019-08-27
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2019.00190
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: Akt Protein Kinase, miR-200/miR-182 Expression and Epithelial-Mesenchymal Transition Proteins in Hibernating Ground Squirrels.

    Lee, Yang-Ja / Bernstock, Joshua D / Klimanis, Dace / Hallenbeck, John M

    Frontiers in molecular neuroscience

    2018  Band 11, Seite(n) 22

    Abstract: Hibernating 13-lined ground squirrels ( ...

    Abstract Hibernating 13-lined ground squirrels (
    Sprache Englisch
    Erscheinungsdatum 2018-01-30
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2018.00022
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  6. Artikel ; Online: Biological networks in ischemic tolerance - rethinking the approach to clinical conditioning.

    Anrather, Josef / Hallenbeck, John M

    Translational stroke research

    2013  Band 4, Heft 1, Seite(n) 114–129

    Abstract: The adaptive response (conditioning) to environmental stressors evokes evolutionarily conserved programs in uni- and multicellular organisms that result in increased fitness and resistance to stressor induced injury. Although the concept of conditioning ... ...

    Abstract The adaptive response (conditioning) to environmental stressors evokes evolutionarily conserved programs in uni- and multicellular organisms that result in increased fitness and resistance to stressor induced injury. Although the concept of conditioning has been around for a while, its translation into clinical therapies targeting neurovascular diseases has only recently begun. The slow pace of clinical adoption might be partially explained by our poor understanding of underpinning mechanisms and of the complex responses of the organism to the stressor. At the 2(nd) Translational Preconditioning Meeting participants engaged in an intense discussion addressing whether the time has come to more aggressively implement clinical conditioning protocols in the treatment of cerebrovascular diseases or whether it would be better to wait until preclinical data would help to minimize clinical empiricism. This review addresses the complex involvement of biological networks in establishing ischemic tolerance at the organism level using two clinically promising conditioning modalities, namely remote ischemic preconditioning, and per- or post-conditioning, as examples.
    Mesh-Begriff(e) Adaptation, Physiological ; Animals ; Brain/blood supply ; Brain Ischemia/metabolism ; Brain Ischemia/therapy ; Clinical Protocols ; Female ; Humans ; Ischemic Postconditioning ; Ischemic Preconditioning ; Male ; Rabbits ; Rats
    Sprache Englisch
    Erscheinungsdatum 2013-09-20
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2541897-X
    ISSN 1868-601X ; 1868-4483
    ISSN (online) 1868-601X
    ISSN 1868-4483
    DOI 10.1007/s12975-012-0244-z
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  7. Artikel ; Online: SUMO and ischemic tolerance.

    Lee, Yang-ja / Hallenbeck, John M

    Neuromolecular medicine

    2013  Band 15, Heft 4, Seite(n) 771–781

    Abstract: Hibernating squirrels slow blood flow to a crawl, but sustain no damage to brain or other tissues. This phenomenon provides an excellent model of natural tolerance to ischemia. Small ubiquitin-like modifier (SUMO) is a 100-residue peptide that modifies ... ...

    Abstract Hibernating squirrels slow blood flow to a crawl, but sustain no damage to brain or other tissues. This phenomenon provides an excellent model of natural tolerance to ischemia. Small ubiquitin-like modifier (SUMO) is a 100-residue peptide that modifies other proteins by being attached to the epsilon amino group of specific lysine residues. The discovery of massive SUMOylation (by both SUMO-1 and SUMO-2/3) occurring in the brains of 13-lined ground squirrels (Ictidomys tridecemlineatus) during hibernation torpor had opened the door to the studies on SUMO and ischemic tolerance reviewed here. Ischemic stress was shown to increase the levels of SUMO conjugation, especially SUMO-2/3, mostly during reperfusion in animal models and during restoration of oxygen and glucose in cell culture systems. Over-expression or depletion of SUMOs and/or Ubc9 (the SUMO E2 conjugating enzyme) increases or decreases (respectively) the levels of SUMO conjugates. Elevated global SUMO conjugations were shown to cytoprotect from ischemic insults; conversely, depressed SUMOylation sensitized cells. Global protein conjugation not only by SUMOs, but also by other ubiquitin-like modifiers (ULMs) including NEDD8, ISG15, UFM1 and FUB1 was shown to be significantly increased in the brains of hibernating ground squirrels during torpor. These increases in multiple ULM conjugations may orchestrate the cellular events in hibernating ground squirrels that induce a state of natural tolerance through their multipronged effects. Certain miRNAs such as the miR-200 family and the miR-182 family were shown, at least partly, to control the levels of these ULM conjugations. Lowering the levels of these miRNAs leads to an increase in global SUMOylation/ULM conjugation, thereby providing the tolerance to ischemia. This suggests that these miRNAs may be good targets for therapeutic intervention in stroke.
    Mesh-Begriff(e) Animals ; Brain Ischemia/physiopathology ; Cells, Cultured ; Cysteine Endopeptidases/physiology ; Disease Models, Animal ; Glucose/metabolism ; Hibernation/physiology ; Humans ; Hypothermia/physiopathology ; Hypothermia, Induced ; Ischemia/physiopathology ; Mice ; Mice, Transgenic ; MicroRNAs/physiology ; Models, Animal ; Nerve Tissue Proteins/physiology ; Neurons/metabolism ; Oxidative Stress ; Rats ; Reperfusion Injury/physiopathology ; Reperfusion Injury/prevention & control ; Sciuridae/physiology ; Small Ubiquitin-Related Modifier Proteins/physiology ; Sumoylation/physiology ; Ubiquitin/metabolism ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/physiology ; Ubiquitins/physiology
    Chemische Substanzen MicroRNAs ; Nerve Tissue Proteins ; Small Ubiquitin-Related Modifier Proteins ; Ubiquitin ; Ubiquitins ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Cysteine Endopeptidases (EC 3.4.22.-) ; ubiquitin-conjugating enzyme UBC9 (EC 6.3.2.-) ; Glucose (IY9XDZ35W2)
    Sprache Englisch
    Erscheinungsdatum 2013-06-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2077809-0
    ISSN 1559-1174 ; 1535-1084
    ISSN (online) 1559-1174
    ISSN 1535-1084
    DOI 10.1007/s12017-013-8239-9
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  8. Artikel: How implementation of systems biology into clinical trials accelerates understanding of diseases.

    Bielekova, Bibiana / Vodovotz, Yoram / An, Gary / Hallenbeck, John

    Frontiers in neurology

    2014  Band 5, Seite(n) 102

    Abstract: Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements ... ...

    Abstract Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.
    Sprache Englisch
    Erscheinungsdatum 2014-06-27
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2014.00102
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: The many faces of tumor necrosis factor in stroke.

    Hallenbeck, John M

    Nature medicine

    2002  Band 8, Heft 12, Seite(n) 1363–1368

    Mesh-Begriff(e) Animals ; Antigens, CD/physiology ; Arteriosclerosis/etiology ; Brain Ischemia/etiology ; Endothelium, Vascular/metabolism ; Humans ; Mice ; Mice, Transgenic ; Receptors, Tumor Necrosis Factor/physiology ; Receptors, Tumor Necrosis Factor, Type I ; Stroke/etiology ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/physiology
    Chemische Substanzen Antigens, CD ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type I ; Tumor Necrosis Factor-alpha
    Sprache Englisch
    Erscheinungsdatum 2002-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm1202-1363
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: Integrative transcriptomic and metabolic analyses of the mammalian hibernating brain identifies a key role for succinate dehydrogenase in ischemic tolerance.

    Bernstock, Joshua D / Willis, Cory M / Garcia-Segura, Monica Emili / Gaude, Edoardo / Anni, Daniela / Lee, Yan-Ja / Thomas, Luke W / Casey, Alva / Vicario, Nunzio / Leonardi, Tommaso / Nicaise, Alexandra M / Gessler, Florian A / Izzy, Saef / Buffelli, Mario R / Seidlitz, Jakob / Srinivasan, Shriya / Murphy, Michael P / Ashcroft, Margaret / Cambiaghi, Marco /
    Hallenbeck, John M / Peruzzotti-Jametti, Luca

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Ischemic stroke results in a loss of tissue homeostasis and integrity, the underlying pathobiology of which stems primarily from the depletion of cellular energy stores and perturbation of available ... ...

    Abstract Ischemic stroke results in a loss of tissue homeostasis and integrity, the underlying pathobiology of which stems primarily from the depletion of cellular energy stores and perturbation of available metabolites
    Sprache Englisch
    Erscheinungsdatum 2023-03-30
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.03.29.534718
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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