blood brain barrier

Summary

Summary: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.

Top Publications

  1. doi The blood-brain barrier in health and chronic neurodegenerative disorders
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical School, Rochester, NY 14642, USA
    Neuron 57:178-201. 2008
  2. ncbi Astrocyte-endothelial interactions at the blood-brain barrier
    N Joan Abbott
    Wolfson Centre for Age Related Diseases, King s College London, UK
    Nat Rev Neurosci 7:41-53. 2006
  3. ncbi The blood-brain barrier: an overview: structure, regulation, and clinical implications
    Praveen Ballabh
    Department of Pediatrics, New York Medical College and Westchester Medical Center, Valhalla, NY 10595, USA
    Neurobiol Dis 16:1-13. 2004
  4. ncbi The blood-brain barrier/neurovascular unit in health and disease
    Brian T Hawkins
    Department of Medical Pharmacology, University of Arizona College of Medicine, Tucson, Arizona, USA
    Pharmacol Rev 57:173-85. 2005
  5. ncbi Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat
    Yi Yang
    Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131 0001, USA
    J Cereb Blood Flow Metab 27:697-709. 2007
  6. ncbi Blood-brain barrier: structural components and function under physiologic and pathologic conditions
    Yuri Persidsky
    Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198 5215, USA
    J Neuroimmune Pharmacol 1:223-36. 2006
  7. ncbi Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats
    Cesario V Borlongan
    Department of Neurology, Medical College of Georgia, 1120 15th Street, BI 3080, Augusta, GA 30912 3200, USA
    Brain Res 1010:108-16. 2004
  8. pmc Blood-brain barrier active efflux transporters: ATP-binding cassette gene family
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover D 30559, Germany
    NeuroRx 2:86-98. 2005
  9. ncbi ABC transporters and the blood-brain barrier
    David J Begley
    Centre for Neuroscience Research, Kings College London, Hodgkin Building, Guy s Campus, London, SE1 1UL, UK
    Curr Pharm Des 10:1295-312. 2004
  10. pmc Methamphetamine alters blood brain barrier permeability via the modulation of tight junction expression: Implication for HIV-1 neuropathogenesis in the context of drug abuse
    Supriya D Mahajan
    Department of Medicine, Division of Allergy, Immunology, and Rheumatology, 301 Multi Research Building, Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, USA
    Brain Res 1203:133-48. 2008

Detail Information

Publications382 found, 100 shown here

  1. doi The blood-brain barrier in health and chronic neurodegenerative disorders
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical School, Rochester, NY 14642, USA
    Neuron 57:178-201. 2008
    ..These findings support developments of new therapeutic approaches for chronic neurodegenerative disorders directed at the BBB and other nonneuronal cells of the neurovascular unit...
  2. ncbi Astrocyte-endothelial interactions at the blood-brain barrier
    N Joan Abbott
    Wolfson Centre for Age Related Diseases, King s College London, UK
    Nat Rev Neurosci 7:41-53. 2006
    ..An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies...
  3. ncbi The blood-brain barrier: an overview: structure, regulation, and clinical implications
    Praveen Ballabh
    Department of Pediatrics, New York Medical College and Westchester Medical Center, Valhalla, NY 10595, USA
    Neurobiol Dis 16:1-13. 2004
    ..Finally, this review describes the pathogenesis of increased BBB permeability in hypoxia-ischemia and inflammatory mechanisms involving the BBB in septic encephalopathy, HIV-induced dementia, multiple sclerosis, and Alzheimer disease...
  4. ncbi The blood-brain barrier/neurovascular unit in health and disease
    Brian T Hawkins
    Department of Medical Pharmacology, University of Arizona College of Medicine, Tucson, Arizona, USA
    Pharmacol Rev 57:173-85. 2005
    ..Therefore, understanding how BBB TJ might be affected by various factors holds significant promise for the prevention and treatment of neurological diseases...
  5. ncbi Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat
    Yi Yang
    Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131 0001, USA
    J Cereb Blood Flow Metab 27:697-709. 2007
    ..Disrupted TJPs previously seen in endothelial cells appeared in the surrounding astrocytes. Our results provide direct evidence that MMPs open the BBB by degrading TJPs and that an MMP inhibitor prevents degradation of the TJPs by MMPs...
  6. ncbi Blood-brain barrier: structural components and function under physiologic and pathologic conditions
    Yuri Persidsky
    Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198 5215, USA
    J Neuroimmune Pharmacol 1:223-36. 2006
    ..Better understanding of tight junction regulation and factors affecting transport systems will allow the development of therapeutics to improve the BBB function in health and disease...
  7. ncbi Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats
    Cesario V Borlongan
    Department of Neurology, Medical College of Georgia, 1120 15th Street, BI 3080, Augusta, GA 30912 3200, USA
    Brain Res 1010:108-16. 2004
    ..These data suggest that early restoration of CBF and BBB following transplantation of BMSCs could mediate the reported functional outcomes in stroke animals...
  8. pmc Blood-brain barrier active efflux transporters: ATP-binding cassette gene family
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover D 30559, Germany
    NeuroRx 2:86-98. 2005
    ..Therefore, modulation of ABC efflux transporters at the BBB forms a novel strategy to enhance the penetration of drugs into the brain and may yield new therapeutic options for drug-resistant CNS diseases...
  9. ncbi ABC transporters and the blood-brain barrier
    David J Begley
    Centre for Neuroscience Research, Kings College London, Hodgkin Building, Guy s Campus, London, SE1 1UL, UK
    Curr Pharm Des 10:1295-312. 2004
    ....
  10. pmc Methamphetamine alters blood brain barrier permeability via the modulation of tight junction expression: Implication for HIV-1 neuropathogenesis in the context of drug abuse
    Supriya D Mahajan
    Department of Medicine, Division of Allergy, Immunology, and Rheumatology, 301 Multi Research Building, Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, USA
    Brain Res 1203:133-48. 2008
    ..of the central nervous system (CNS) by HIV-1 infected mononuclear cells that transmigrate across the blood brain barrier (BBB)...
  11. ncbi Tight junctions of the blood-brain barrier: development, composition and regulation
    Hartwig Wolburg
    Institute of Pathology, University of Tubingen, Liebermeisterstr 8, D 72076 Tubingen, Germany
    Vascul Pharmacol 38:323-37. 2002
    ..4. Important new molecular aspects of tight junction regulation were recently elucidated. This review provides an integration of these new results...
  12. ncbi Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme
    Hartwig Wolburg
    Institute for Pathology, University of Tubingen, Liebermeisterstrasse 8, 72076, Tubingen, Germany
    Acta Neuropathol 105:586-92. 2003
    ....
  13. ncbi Inflammatory mediators and modulation of blood-brain barrier permeability
    N J Abbott
    Division of Physiology, GKT School of Biomedical Sciences, King s College London, UK
    Cell Mol Neurobiol 20:131-47. 2000
    ....
  14. ncbi Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier
    J D Huber
    Department of Pharmacology, The University of Arizona College of Medicine, Tucson, AZ 85724, USA
    Trends Neurosci 24:719-25. 2001
    ..By allowing the "loosening" of TJs and an increase in paracellular permeability, the BBB is able to "bend without breaking"; thereby, maintaining structural integrity...
  15. ncbi Blood-brain barrier-specific properties of a human adult brain endothelial cell line
    B B Weksler
    Institut Cochin, CNRS UMR 8104 INSERM U567, Universite Rene Descartes, Paris, France
    FASEB J 19:1872-4. 2005
    ..Thus, hCMEC/D3 represents the first stable, fully characterized, well-differentiated human brain endothelial cell line and should serve as a widely usable research tool...
  16. ncbi Strategies to advance translational research into brain barriers
    Edward Neuwelt
    Oregon Health and Science University, Department of Neurology, Veterans Administration Medical Center, Portland, OR, USA
    Lancet Neurol 7:84-96. 2008
    ..At a recent meeting of expert panels, essential and high-priority recommendations to propel brain barrier research forward in six topical areas were developed and these recommendations are presented here...
  17. pmc Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein
    Manuel Yepes
    Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    J Clin Invest 112:1533-40. 2003
    ....
  18. pmc MMP-9 gene silencing by a quantum dot-siRNA nanoplex delivery to maintain the integrity of the blood brain barrier
    Adela Bonoiu
    Institute for Lasers, Photonics and Biophotonics, University at Buffalo, The State University of New York, Buffalo, New York, 14260 3000, USA
    Brain Res 1282:142-55. 2009
    ..MMPs), particularly MMP-9, are involved in the neuroinflammation processes leading to disrupting of the blood brain barrier (BBB), thereby exacerbating neurological diseases such as HIV-1 AIDS dementia and cerebral ischemia...
  19. ncbi Blood-brain barrier dysfunction in parkinsonian midbrain in vivo
    Rudie Kortekaas
    Department of Neurology, Groningen University Hospital, Groningen, The Netherlands
    Ann Neurol 57:176-9. 2005
    ..Here, we show significantly elevated uptake of [(11)C]-verapamil (18%) in the midbrain of PD patients relative to controls. This is the first evidence supporting a dysfunctional blood-brain barrier as a causative mechanism in PD...
  20. ncbi Microvascular injury and blood-brain barrier leakage in Alzheimer's disease
    B D Zipser
    Department of Pathology Neuropathology Division, Brown Medical School, Rhode Island Hospital, Providence, RI 02903, United States
    Neurobiol Aging 28:977-86. 2007
    ....
  21. pmc Seizure-promoting effect of blood-brain barrier disruption
    Nicola Marchi
    Cerebrovascular Research Center, Department of Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Epilepsia 48:732-42. 2007
    ..However, evidences also suggest that BBB failure may be an etiological factor contributing to the development of seizures...
  22. pmc The blood-brain barrier: bottleneck in brain drug development
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    NeuroRx 2:3-14. 2005
    ..This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences...
  23. pmc Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models
    Carlos J Orihuela
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    J Clin Invest 119:1638-46. 2009
    ..influenzae, but the mechanism by which they initiate contact with the vascular endothelium of the blood brain barrier (BBB) is unknown. We hypothesized that an interaction with LR might underlie their CNS tropism...
  24. ncbi Nanoparticle surface charges alter blood-brain barrier integrity and permeability
    Paul R Lockman
    Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106 1712, USA
    J Drug Target 12:635-41. 2004
    ..NPs were characterized by particle size and zeta potential. BBB integrity and NP brain permeability were evaluated by in situ rat brain perfusion...
  25. ncbi Molecular targets in radiation-induced blood-brain barrier disruption
    Robert A Nordal
    Department of Radiation Oncology, Sunnybrook and Women s College Health Sciences Centre, University of Toronto, Toronto, Ontario Canada
    Int J Radiat Oncol Biol Phys 62:279-87. 2005
    ..These processes implicate particular genes and proteins as targets in potential strategies for neuroprotection...
  26. ncbi Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain
    Ian Galea
    CNS Inflammation Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
    Glia 49:375-84. 2005
    ....
  27. ncbi Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bunteweg 17, D 30559 Hannover, Germany
    Prog Neurobiol 76:22-76. 2005
    ..Finally, we summarize strategies for modulating or by-passing drug efflux transporters at the BBB as novel therapeutic approaches to drug-resistant brain diseases...
  28. pmc Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier
    Omid Veiseh
    Departments of Materials Science and Engineering, University of Washington, Seattle, Washington 99195, USA
    Cancer Res 69:6200-7. 2009
    ....
  29. ncbi Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications
    S I Rapoport
    Section on Brain Physiology and Metabolism, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell Mol Neurobiol 20:217-30. 2000
    ..The method also has been used together with anticancer drugs to treat patients with metastatic or primary brain tumors, with some success and minimal morbidity...
  30. pmc Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions
    B Dubois
    Rega Institute for Medical Research, University of Leuven, B 3000 Leuven, Belgium
    J Clin Invest 104:1507-15. 1999
    ..These data illustrate that gelatinase B expression plays a role in the development of the immune system and that, in ontogenesis, the propensity to develop autoimmunity is altered by the absence of this MMP...
  31. pmc Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke
    Albert Y Jin
    Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
    BMC Neurosci 11:12. 2010
    ..In vivo assessment of BBB dysfunction was also investigated optically using intravital microscopy of the pial circulation following the injection of Fluorescein Isothiocyanate (FITC)-dextran (MW 2000 kDa)...
  32. doi The blood-brain barrier is continuously open for several weeks following transient focal cerebral ischemia
    D Strbian
    Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland
    Neuroscience 153:175-81. 2008
    ..This is the first systematic and extensive study fully demonstrating BBB leakage dynamics following transient brain ischemia and the findings are of major clinical and experimental interest...
  33. ncbi Targeted delivery of antibodies through the blood-brain barrier by MRI-guided focused ultrasound
    Manabu Kinoshita
    Department of Radiology, Brigham and Womens Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Biochem Biophys Res Commun 340:1085-90. 2006
    ..Using MRI, we were able to monitor the extent of BBB disruption. This novel technology should be useful in delivering macromolecular therapeutic or diagnostic agents to the CNS for the treatment of various CNS disorders...
  34. ncbi Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier
    Hans Joachim Stemmler
    Medical Department III, Ludwig Maximilians University of Munich, Clinic Grosshadern, Munich, Germany
    Anticancer Drugs 18:23-8. 2007
    ....
  35. ncbi Clearing amyloid through the blood-brain barrier
    Berislav V Zlokovic
    Frank P Smith Laboratories for Neuroscience, Department of Neurological Surgery, University of Rochester Medical Center, New York 14642, USA
    J Neurochem 89:807-11. 2004
    ..Thus, understanding A beta exchanges between brain and blood, and vice versa, and developing transport-based systemic A beta-lowering strategies may provide new important insights into pathogenesis and therapeutic control of AD...
  36. pmc Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier
    Caroline Charlier
    Unité de Mycologie Moléculaire, CNRS FRE2948, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    Am J Pathol 166:421-32. 2005
    ..The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces...
  37. ncbi Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy
    Teresa Ravizza
    Department of Neuroscience, Laboratory of Experimental Neurology, Mario Negri Institute for Pharmacological Research, Milano, Italy
    Neurobiol Dis 29:142-60. 2008
    ..These data show that specific inflammatory pathways are chronically activated during epileptogenesis and they persist in chronic epileptic tissue, suggesting they may contribute to the etiopathogenesis of TLE...
  38. ncbi Flavonoid permeability across an in situ model of the blood-brain barrier
    Kuresh A Youdim
    Antioxidant Research Group, Wolfson Centre for Age Related Diseases, Centre for Neuroscience Research, Guy s King s and St Thomas s School of Biomedical Sciences, King s College, London SE1 1UL, UK
    Free Radic Biol Med 36:592-604. 2004
    ..In conclusion, the results demonstrate that flavonoids are able to traverse the BBB in vivo. However, the permeability of certain flavonoids in vivo is influenced by their lipophilicity and interactions with efflux transporters...
  39. pmc Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: preserving the blood brain barrier via an interaction with splenocytes
    Peter A Walker
    Department of Surgery, University of Texas Medical School at Houston, Houston, TX, USA
    Exp Neurol 225:341-52. 2010
    ..brain injury through an interaction with resident splenocytes, subsequently leading to preservation of the blood brain barrier. Four groups of rats underwent controlled cortical impact injury (3 groups) or sham injury (1 group)...
  40. ncbi Brain inflammation in epilepsy: experimental and clinical evidence
    Annamaria Vezzani
    Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Epilepsia 46:1724-43. 2005
    ..The elucidation of this aspect may open new perspectives for the pharmacologic treatment of seizures...
  41. pmc Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid
    Kelly S Doran
    Department of Pediatrics, Division of Infectious Diseases, UCSD School of Medicine, La Jolla, California 92093, USA
    J Clin Invest 115:2499-507. 2005
    ..Our data suggest that LTA expression on the GBS surface plays a role in bacterial interaction with BBB endothelium and the pathogenesis of neonatal meningitis...
  42. ncbi Blood-brain barrier tight junctions are altered during a 72-h exposure to lambda-carrageenan-induced inflammatory pain
    J D Huber
    Department of Pharmacology, University of Arizona College of Medicine, Tucson 85724, USA
    Am J Physiol Heart Circ Physiol 283:H1531-7. 2002
    ..Changes in the structure of tight junctions may have important clinical ramifications concerning central nervous system homeostasis and therapeutic drug delivery...
  43. ncbi Puromycin-purified rat brain microvascular endothelial cell cultures exhibit improved barrier properties in response to glucocorticoid induction
    Anthony R Calabria
    Department of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Neurochem 97:922-33. 2006
    ..The combined use of puromycin and glucocorticoid therefore provides an in vitro system that is well suited for molecular level BBB investigations...
  44. pmc Blood-brain barrier transport of therapeutics via receptor-mediation
    Angela R Jones
    Department of Chemical and Biological Engineering, University of Wisconsin Madison, 1415 Engineering Drive, Madison, Wisconsin 53706, USA
    Pharm Res 24:1759-71. 2007
    ..Over the last decade, there have been significant developments in the arena of RMT-based brain drug transport, and this review will focus on those approaches that have been validated in an in vivo setting...
  45. doi Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease
    Yin Xia Chao
    Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    J Neuroimmunol 216:39-50. 2009
    ..of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB)...
  46. pmc TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1
    Jessy J Alexander
    Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC5100, Chicago, IL 60637, USA
    Neurochem Int 52:447-56. 2008
    ....
  47. pmc A new function for the LDL receptor: transcytosis of LDL across the blood-brain barrier
    B Dehouck
    Institut National de la Santé et de la Recherche Médicale U325, Department of Atherosclerosis Institut Pasteur, Lille, France
    J Cell Biol 138:877-89. 1997
    ..Preliminary studies suggest that caveolae are likely to be involved in the potential transport of LDL from the blood to the brain...
  48. ncbi Circumventricular organs: definition and role in the regulation of endocrine and autonomic function
    W F Ganong
    Department of Physiology, University of California, San Francisco 94143 0444, USA
    Clin Exp Pharmacol Physiol 27:422-7. 2000
    ..Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion...
  49. ncbi Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone and progesterone into the brain is enhanced in mice deficient for both mdr1a and mdr1b P-glycoproteins
    M Uhr
    Max Planck Institute of Psychiatry, Munich, Germany
    J Neuroendocrinol 14:753-9. 2002
    ....
  50. ncbi MMPs contribute to TNF-alpha-induced alteration of the blood-cerebrospinal fluid barrier in vitro
    Patrick Zeni
    Institut fur Biochemie, Westfalische Wilhelms Universitat, Wilhelm Klemm Strasse 2, D 48149 Munster, Germany
    Am J Physiol Cell Physiol 293:C855-64. 2007
    ..Thus TNF-alpha may mediate the binding of leukocytes to cellular adhesion molecules and the transmigration across the blood-CSF barrier...
  51. ncbi Nanoparticle technology for drug delivery across the blood-brain barrier
    P R Lockman
    Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo 79106 1712, USA
    Drug Dev Ind Pharm 28:1-13. 2002
    ..NP technology appears to have significant promise in delivering therapeutic molecules across the BBB...
  52. ncbi Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs
    Luca Cucullo
    Center for Cerebrovascular Research, Cleveland, Ohio, USA
    Epilepsia 48:505-16. 2007
    ....
  53. pmc Hypoxia disrupts the barrier function of neural blood vessels through changes in the expression of claudin-5 in endothelial cells
    Takashi Koto
    Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Am J Pathol 170:1389-97. 2007
    ..These in vitro and in vivo data indicate that claudin-5 is a target molecule of hypoxia leading to the disruption of the barrier function of neural vasculature...
  54. ncbi The source of cerebral insulin
    William A Banks
    Research Service 151, GRECC, Veterans Affairs Medical Center St Louis and Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, WAB, 915 N Grand Boulevard, St Louis, MO 63106, USA
    Eur J Pharmacol 490:5-12. 2004
    ..Insulin itself also has effects on the BBB, altering enzymatic and transporter functions. Overall, BBB transport of insulin provides a mechanism for peripheral insulin to act within the CNS as a regulatory peptide...
  55. pmc Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy
    David S Miller
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Pharmacol Rev 60:196-209. 2008
    ..Finally, several steps in signaling are potential therapeutic targets that could be used to modulate P-glycoprotein activity in the clinic...
  56. ncbi Barrier mechanisms in the brain, II. Immature brain
    N R Saunders
    Department of Anatomy and Physiology, University of Tasmania, Hobart, Australia
    Clin Exp Pharmacol Physiol 26:85-91. 1999
    ..7. Permeability to small lipid-insoluble molecules is greater in developing brain; more specific mechanisms, such as those involved in transfer of ions and amino acids, develop sequentially as the brain grows...
  57. pmc Induction of blood brain barrier tight junction protein alterations by CD8 T cells
    Georgette L Suidan
    Neuroscience Department, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 3:e3037. 2008
    Disruption of the blood brain barrier (BBB) is a hallmark feature of immune-mediated neurological disorders as diverse as viral hemorrhagic fevers, cerebral malaria and acute hemorrhagic leukoencephalitis...
  58. ncbi Microbial translocation of the blood-brain barrier
    Kwang Sik Kim
    Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 256, Baltimore, MD 21287, USA
    Int J Parasitol 36:607-14. 2006
    ..This review summarises our current understanding of the pathogenic mechanisms involved in translocation of the BBB by meningitis-causing bacteria, fungi and parasites...
  59. pmc Reproductive age-related changes in the blood brain barrier: expression of IgG and tight junction proteins
    Shameena Bake
    Department of Neuroscience and Experimental Therapeutics, TAMHSC College of Medicine, College Station, TX 77843, USA
    Microvasc Res 78:413-24. 2009
    ..the forebrain of acyclic (reproductive senescent) females compared to young adult females, indicating that blood brain barrier permeability is compromised in the reproductive senescent forebrain...
  60. pmc Enhancing the delivery of anti retroviral drug "Saquinavir" across the blood brain barrier using nanoparticles
    Supriya D Mahajan
    Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Buffalo General Hospital, Buffalo, NY 14203, USA
    Curr HIV Res 8:396-404. 2010
    ..transferrin (Tf), these drug-loaded nanoformulations can permeate across biological barriers such as the blood brain barrier (BBB) via a receptor mediated transport mechanism...
  61. ncbi Pericytes: pluripotent cells of the blood brain barrier
    Paula Dore-Duffy
    Department of Neurology, Wayne State University School of Medicine, 421 East Canfield Avenue, 3126 Elliman Clinical Research Building, Detroit, Michigan 48201, USA
    Curr Pharm Des 14:1581-93. 2008
    ..We will also speculate on the importance of pericyte stem cell activity in survival and DNA repair and how dysregulation of pericyte function may lead to disease...
  62. doi Blood-brain barrier tight junction permeability and ischemic stroke
    Karin E Sandoval
    Department of Pharmaceutical Sciences, School of Pharmacy, Southern Illinois University Edwardsville, Edwardsville, IL 62026, USA
    Neurobiol Dis 32:200-19. 2008
    ..This review focuses on those aspects of ischemic stroke impacting BBB TJ integrity and the principle regulatory pathways, respective to the phases of paracellular permeability...
  63. ncbi Ischemic brain edema
    G A Rosenberg
    Department of Neurology, University of New Mexico, Albuquerque 87131, USA
    Prog Cardiovasc Dis 42:209-16. 1999
    ..As the molecular events become clearer, novel treatments that block different stages of the injury cascade will be available for clinical testing...
  64. doi Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood-brain interfaces
    Silvia Gazzin
    INSERM U842, Universite de Lyon, Lyon 1, Faculte de Medecine Laennec, F 69372 Lyon, France
    J Comp Neurol 510:497-507. 2008
    ..The data also highlight the significance of the neuroprotective function of the choroid plexus during brain maturation, when the microvasculature is still developing...
  65. ncbi Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain
    Jorg Kreuter
    Institut fur Pharmazeutische Technologie, Biozentrum, Johann Wolfgang Goethe Universitat Frankfurt, Germany
    J Control Release 118:54-8. 2007
    ..This result demonstrates that more than one mechanism is involved in the interaction of nanoparticles with the brain endothelial cells and the resulting delivery of drugs to the central nervous system...
  66. ncbi Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs
    Kelly M Mahar Doan
    Preclinical Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA
    J Pharmacol Exp Ther 303:1029-37. 2002
    ..For CNS delivery, a drug should ideally have an in vitro passive permeability >150 nm/s and not be a good (B --> A/A --> B ratio <2.5) Pgp substrate...
  67. ncbi Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs
    J Kelder
    Department of Molecular Design and Informatics, NV Organon, Oss, The Netherlands
    Pharm Res 16:1514-9. 1999
    ..To study oral absorption and brain penetration as a function of polar molecular surface area...
  68. pmc Brain angiogenesis in developmental and pathological processes: neurovascular injury and angiogenic recovery after stroke
    Ken Arai
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    FEBS J 276:4644-52. 2009
    ..Understanding how neurovascular signals and substrates make the transition from initial injury to angiogenic recovery will be important if we are to find new therapeutic approaches for stroke...
  69. ncbi Blood-brain barrier targeting of BDNF improves motor function in rats with middle cerebral artery occlusion
    Yun Zhang
    Department of Medicine, UCLA Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Brain Res 1111:227-9. 2006
    ....
  70. ncbi Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination
    John Kirk
    School of Medicine Inflammation Research Centre, Queen s University of Belfast, Northern Ireland, UK
    J Pathol 201:319-27. 2003
    ..In NAWM, it suggests either pre-lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease-modifying therapy...
  71. ncbi Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
    A H Schinkel
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam
    Cell 77:491-502. 1994
    ....
  72. ncbi Delivery of therapeutic agents to the central nervous system: the problems and the possibilities
    David J Begley
    Blood Brain Barrier Research Group, GKT School of Biomedical Science, Guy s Campus, King s College London, Hodgkin Building, London SE1 1UL, UK
    Pharmacol Ther 104:29-45. 2004
    ..The various strategies available and under development for enhancing drug delivery to the CNS are reviewed...
  73. ncbi Impaired transport of leptin across the blood-brain barrier in obesity
    W A Banks
    GRECC, Veterans Affairs Medical Center St Louis and Saint Louis University School of Medicine, Department of Internal Medicine, MO 63106, USA
    Peptides 20:1341-5. 1999
    ..This suggests a new model for obesity in which a defect in the BBB transport of leptin into the CNS underlies the insensitivity to leptin and leads to obesity...
  74. ncbi Brain endothelial cell production of a neuroprotective cytokine, interleukin-6, in response to noxious stimuli
    T M Reyes
    Department of Psychology, University of Wisconsin, Madison 53706, USA
    Brain Res 851:215-20. 1999
    ..This research indicates a pathway whereby immune signals may be communicated to the CNS and has revealed one way that the BBB may protect neuronal survival under challenge conditions...
  75. ncbi Barriers in the immature brain
    N R Saunders
    University of Tasmania, Australia
    Cell Mol Neurobiol 20:29-40. 2000
    ....
  76. ncbi Role of multidrug transporters in pharmacoresistance to antiepileptic drugs
    Wolfgang Loscher
    Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany
    J Pharmacol Exp Ther 301:7-14. 2002
    ..Furthermore, there are certainly other mechanisms of pharmacoresistance that need to be identified...
  77. ncbi Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging
    Martin Rausch
    Novartis Institute for Biomedical Research, Basel, Switzerland
    J Magn Reson Imaging 20:16-24. 2004
    ..To examine the efficacy of FTY720 as a new agent to reduce inflammatory activity in an animal model of multiple sclerosis (MS) by in vivo macrophage tracking...
  78. ncbi Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion
    Thomas Pfefferkorn
    Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
    Stroke 34:2025-30. 2003
    ..We hypothesized that rtPA-mediated adverse effects depend on the timing of reperfusion and injury to the blood-brain barrier (BBB)...
  79. ncbi Innate response to focal necrotic injury inside the blood-brain barrier
    Jiyun V Kim
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Immunol 177:5269-77. 2006
    ..The astrocytes network established a cytoplasmic Ca2+ gradient that preceded the microglial response. This is consistent with astrocyte-microglial collaboration to mount this innate response that excludes blood leukocytes...
  80. ncbi Migration of African trypanosomes across the blood-brain barrier
    Willias Masocha
    Karolinska Institutet, Department of Neuroscience, S 171 77 Stockholm, Sweden
    Physiol Behav 92:110-4. 2007
    ....
  81. ncbi Drug transport at the blood-brain barrier and the choroid plexus
    Candace L Graff
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Curr Drug Metab 5:95-108. 2004
    ..Potential approaches to increasing both net CNS and target-site exposure, when such exposure is dictated by efflux transport, are considered...
  82. pmc Mannose 6-phosphate receptor-mediated transport of sulfamidase across the blood-brain barrier in the newborn mouse
    Akihiko Urayama
    Department of Neurology, Laboratory of Protein Misfolding Disorders, University of Texas Medical Branch, Galveston, Texas, USA
    Mol Ther 16:1261-6. 2008
    ..That is, the transport of sulfamidase into the brain parenchyma in early postnatal life is mediated by the M6P receptor, which is shared with P-GUS and is likely accessible to other M6P-containing lysosomal enzymes...
  83. doi All vertebrates started out with a glial blood-brain barrier 4-500 million years ago
    Magnus Bundgaard
    Department of Medical Physiology, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    Glia 56:699-708. 2008
    ..There are important implications for the development, physiology, and pathology of the mammalian BBB, and for the roles of endothelium and glia in CNS barrier layers...
  84. pmc ApoE deficiency compromises the blood brain barrier especially after injury
    N Methia
    The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Mol Med 7:810-5. 2001
    ..Astrocytes that induce blood brain barrier (BBB) properties in endothelium also produce apoE...
  85. pmc Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers
    B V Zlokovic
    Department of Neurological Surgery, Childrens Hospital, Los Angeles, CA, USA
    Proc Natl Acad Sci U S A 93:4229-34. 1996
    ..The findings suggest that gp330/megalin mediates cellular uptake and transport of apoJ and sA beta (1-40)-apoJ complex at the cerebral vascular endothelium and choroid epithelium...
  86. ncbi Potential role of ABC transporters as a detoxification system at the blood-CSF barrier
    Elizabeth C M de Lange
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Gorlaeus Laboratoria, Leiden University, PO Box 9502, 2300RA Leiden, The Netherlands
    Adv Drug Deliv Rev 56:1793-809. 2004
    ..A concerted action of P-gp and MRP1 at the choroid plexus might contribute to the maintenance of the role of the BCSFB in brain homeostasis...
  87. ncbi Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction
    James Haorah
    Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198 5215, USA
    J Neurochem 101:566-76. 2007
    ..These findings point to new therapeutic interventions ameliorating BBB dysfunction in neurological disorders such as stroke or neuroinflammation...
  88. ncbi Bacterial penetration across the blood-brain barrier during the development of neonatal meningitis
    S H Huang
    Division of Infectious Diseases, Childrens Hospital Los Angeles and the University of Southern California, Los Angeles, CA 90027, USA
    Microbes Infect 2:1237-44. 2000
    ..coli K1 genes ompA, ibeA, ibeB, and yijP. Understanding the mechanisms of bacterial penetration across the BBB may help develop novel approaches to preventing bacterial meningitis...
  89. ncbi Differential susceptibility of cerebral and cerebellar murine brain microvascular endothelial cells to loss of barrier properties in response to inflammatory stimuli
    Christine Silwedel
    Institute of Anatomy and Cell Biology, University of Wurzburg, Koellikerstrasse 6, Wurzburg, Germany
    J Neuroimmunol 179:37-45. 2006
    ..The molecular pathogenesis of MS includes an increased permeability of the blood brain barrier (BBB) along with an inability of the BBB to fulfill its normal function of protecting the CNS...
  90. pmc Occludin as direct target for glucocorticoid-induced improvement of blood-brain barrier properties in a murine in vitro system
    Carola Förster
    Institute of Anatomy and Cell Biology, University of Wurzburg, Koellikerstrasse 6, D 97070 Wurzburg, Germany
    J Physiol 565:475-86. 2005
    ..This study thus provides insights into the molecular processes of barrier genesis, and may help to elucidate mechanisms of brain pathology at the microvascular level...
  91. ncbi Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment
    C Avolio
    Department of Medical and Occupational Sciences, University of Foggia, Foggia, Italy
    Mult Scler 11:441-6. 2005
    ..85; P < 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TMIP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS...
  92. pmc Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice
    Takehiro Nitta
    Department of Cell Biology, Faculty of Medicine, Kyoto University, Japan
    J Cell Biol 161:653-60. 2003
    ..e., the size-selective loosening of the BBB) not only provides new insight into the basic molecular physiology of BBB but also opens a new way to deliver potential drugs across the BBB into the central nervous system...
  93. pmc IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel
    Vanda A Lennon
    Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Exp Med 202:473-7. 2005
    ..NMO may represent the first example of a novel class of autoimmune channelopathy...
  94. ncbi Reducing cerebral microvascular amyloid-beta protein deposition diminishes regional neuroinflammation in vasculotropic mutant amyloid precursor protein transgenic mice
    Jianting Miao
    Department of Medicine, Stony Brook University, Stony Brook, New York 11794 8153, USA
    J Neurosci 25:6271-7. 2005
    ....
  95. ncbi Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice
    C Dagenais
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, USA
    J Cereb Blood Flow Metab 20:381-6. 2000
    ..These data suggest that the model is applicable to elucidating the effects of efflux transporters, including Pgp, on brain uptake...
  96. ncbi Functional expression and localization of P-glycoprotein at the blood brain barrier
    Reina Bendayan
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
    Microsc Res Tech 57:365-80. 2002
    ....
  97. ncbi Effects of the chemokine CCL2 on blood-brain barrier permeability during ischemia-reperfusion injury
    Oliver B Dimitrijevic
    Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109 0532, USA
    J Cereb Blood Flow Metab 26:797-810. 2006
    ..These data suggest CCL2/CCR2 has an important role in regulating brain endothelial permeability and might be a potential novel therapeutic target for stroke...
  98. ncbi Dynamics of CNS barriers: evolution, differentiation, and modulation
    N Joan Abbott
    Blood Brain Barrier Group, Wolfson Centre for Age Related Diseases, King s College University of London, London, UK
    Cell Mol Neurobiol 25:5-23. 2005
    ..Less is known about the modulation of the CP. (6) The challenge for the next era of CNS barrier studies will be to apply new knowledge from proteomics and genomics to understanding the in vivo condition in physiology and pathology...
  99. ncbi Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration
    Wei Lu
    Department of Pharmaceutics, School of Pharmacy, Fudan University Fenglin Campus, P O Box 130, 138 Yi Xue Yuan Road, Shanghai 200032, P R China
    Cancer Res 66:11878-87. 2006
    ..v. injections of CBSA-NP-hTRAIL induced apoptosis in vivo and significantly delayed tumor growth. In summary, this study indicates that CBSA-NP-hTRAIL is a promising candidate for noninvasive gene therapy of malignant glioma...
  100. ncbi [An experimental study on distribution of musk into the brain through blood brain barrier]
    Wen Kai Chen
    Division of Zang fu Organs Research, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province 210029, China
    Zhong Xi Yi Jie He Xue Bao 2:288-91. 2004
    To study the possible pathway of the effect of musk on brain disorder, distributing into the brain through blood brain barrier.
  101. ncbi Receptor-mediated transport of LIF across blood-spinal cord barrier is upregulated after spinal cord injury
    Weihong Pan
    Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA
    J Neuroimmunol 174:119-25. 2006
    ..This enhanced transport correlated with increased expression of LIFRalpha shown by immunofluorescent staining and Western blot. Therefore, LIFR at the BBB provides an important target for therapeutic intervention...

Research Grants78

  1. Brain mast cells and Chronic Fatigue Syndrome
    Theoharis C Theoharides; Fiscal Year: 2013
    ..The proposed research is hypothesis-driven, is based on strong preliminary evidence, is innovative with high likelihood for novel findings with applicability to humans. ..
  2. Multi-targeted Countermeasures against Acute and Delayed Effects of OP Exposure
    John A Butera; Fiscal Year: 2013
    ..synthesis of dual agents with suitable pharmaceutical profiles, such that they will be able to cross the blood brain barrier, a desired feature that is lacking from current AChE reactivators...
  3. Neuroprotection and Myelin Repair Mechanisms in Multiple Sclerosis
    Inderjit Singh; Fiscal Year: 2013
    ..metformin attenuates EAE disease and provides neuro-protection via immunomodulation and protection of the blood brain barrier (BBB)...
  4. Role of CD44 in experimental Multiple Sclerosis
    Mitzi Nagarkatti; Fiscal Year: 2013
    ..abstract_text> ..
  5. Drug Interactions at the Human Blood-Brain Barrier
    Jashvant D Unadkat; Fiscal Year: 2010
    ..The blood brain barrier (BBB) is a significant barrier to delivery of drugs to the central nervous system (CNS) and in removal of ..
  6. Tumor Microenvironment Interactions in Brain Tumors
    Eric C Holland; Fiscal Year: 2010
    ..Brain metastasis requires that tumor cells break through a unique physiological barrier, the blood brain barrier (BBB)...
  7. Overcoming Temozolomide Resistance using MGMT-targeting Spherical Nucleic Acids
    TIMOTHY L SITA; Fiscal Year: 2013
    ..In vivo studies with orthotopic GBM mouse models will assess the combination treatment of MGMTi-SNAs and TMZ;we intend to (1) enhance intratumoral apoptosis, (2) reduce glioma formation, and (3) increase survival time. ..
  8. N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus Infecti
    Aquilur Rahman; Fiscal Year: 2013
    ....
  9. Protection of Brain Injury from Cyanide Poisoning by Carnosic Acid
    Stuart A Lipton; Fiscal Year: 2013
    ..To investigate neuroprotective effects of CA in an in vitro model of cyanide poisoning. Specific Aim 2. To examine neuroprotective effects of CA in an in vivo mouse model mimicking the effects of cyanide ingestion. ..
  10. Neuroprotection by IFN-beta in AIDS
    Marcus Kaul; Fiscal Year: 2013
    ..For Specific Aim 1, IFN? will be administered via an intranasal route, which largely allows bypassing the blood brain barrier while delivering the drug to the brain...
  11. Intranasal CNS delivery of drugs against organophosphorous threat agents
    ARYAN MANGALAM NAMBOODIRI; Fiscal Year: 2013
    ..The successful use of an intranasal brain delivery technology against chemical threat agents will open up its wider application in numerous other areas of clinical medicine and research. ..
  12. Brain Delivery of Nanoformulated Superoxide Dismutase
    Erin G Rosenbaugh; Fiscal Year: 2013
    ..In addition to the proposed scientific research, this fellowship will support the applicant's participation in nanotechnology-based coursework and career development. ..
  13. Mechanisms Regulating Reduced c-Kit-Dependent EAE Susceptibility in Male SJL Mice
    MELISSA ANN BROWN; Fiscal Year: 2013
    ..These mice provide a perfect system to explore the how c-kit signaling, in concert with influences from male sex hormones, confers neuroprotection and may lead to better therapies for this devastating CNS disease. ..
  14. Role of Vimentin in Pathogenesis of CNS Inflammation
    Sheng He Huang; Fiscal Year: 2013
    ..2). Determine how Vim and PSF contribute to IbeA-induced pathogen penetration and PMN transmigration across the BBB by SCP analysis of cBMEC and genetic blockage of Vim. ..
  15. Effects of brain-selective estradiol on gene expression and female sex behavior
    Kim Wallen; Fiscal Year: 2013
    ..DHED, which crosses the blood brain barrier, would be inactive outside of the brain, but would deliver effective amounts of E2 to the brain...
  16. Engineering the Brain Immune System for Tumor Therapy
    Maria G Castro; Fiscal Year: 2013
    ....
  17. Control of Drug Delivery to the CNS: Modulating P-glycoprotein Activity
    William A Banks; Fiscal Year: 2013
    ..abstract_text> ..
  18. Studying a novel regulator of GBM tumorigeneis: the role of CK2alpha in maintaini
    Gordon Li; Fiscal Year: 2013
    ..abstract_text> ..
  19. Preclinical testing of a novel PDK1 inhibitor for treating vestibular schwannoma
    Abraham Jacob; Fiscal Year: 2013
    ..drug administration in order to sustain efficacy, we plan to evaluate clinically relevant pharmacodynamic (blood brain barrier penetration) and pharmacotoxicity (blood chemistries and organ toxicity) profiles for OSU-03012 during long-..
  20. Nanomedicine and NeuroAIDS
    Howard E Gendelman; Fiscal Year: 2013
    ..The overall premise is to develop the necessary "state of the art" tools to improve nanoART induced viral reduction in its CNS and other viral reservoirs. ..
  21. Immune Regulation of Viral Recrudescence
    Cornelia Bergmann; Fiscal Year: 2012
    ..ASC within the CNS, to combat infections where virus replicates in the CNS in the absence of overt blood brain barrier damage or inflammatory signals...
  22. Early Disease Biomarkers of PCB-exposed Human Population
    Sisir K Dutta; Fiscal Year: 2010
    ....
  23. Energy Balance During Ketosis in Rat Brain
    JOSEPH CHARLES LAMANNA; Fiscal Year: 2010
    ..The enzymes for ketone metabolism and the monocarboxylate transporters at the blood brain barrier are known to increase with fasting or ketogenic diet...
  24. White matter changes in HIV models
    Pamela E Knapp; Fiscal Year: 2011
    ..It was historically attributed to vasculitis and subsequent blood brain barrier leakage...
  25. Neuronal mRNA PET Imaging
    Eric Wickstrom; Fiscal Year: 2010
    ..In the future, beyond the scope of this proposal, nuclear medicine imaging of brain cell gene activity in humans might explain why some individuals become addicted more easily than others. ..
  26. White Matter Protection in Cerebral Ischemia
    Guodong Cao; Fiscal Year: 2013
    ..More importantly, we found that exogenously administered NAMPT protein can cross the blood brain barrier and protect against ischemic WMI in vivo...
  27. Neuroimmune modulation across the BBB: Regulation of ILS trafficking by TNF
    Weihong Pan; Fiscal Year: 2012
    ..Their interactions with the blood-brain barrier largely determine the final outcome of these blood-borne cytokines. ..
  28. Drug Transport at the Blood-Testis Barrier
    Nathan J Cherrington; Fiscal Year: 2013
    ....
  29. METABOLIC CONTROL OF SUGAR TRANSPORT
    Anthony Carruthers; Fiscal Year: 2012
    ..Specific Aim 4 tests the hypothesis that rapid up-regulation of erythrocyte and blood brain barrier endothelial cell sugar transport represent a single fundamental GLUT1 regulatory mechanism by comparison of ..
  30. Experimental Optic Neuritis: Gene Therapy
    John Guy; Fiscal Year: 2011
    ..The proposed study in mice is designed to develop a strategy to treat patients at risk for axonal degeneration and persistent visual loss from optic neuritis and multiple sclerosis. ..
  31. Prophage-associated virulence factors in pathogenic Neisseria species
    ANNA KARLS; Fiscal Year: 2009
    ..Despite the use of chemotherapeutics, 10-40% of invasive meningococcal infections are fatal and 10-15% of survivors have serious sequelae, including mental retardation and deafness. ..
  32. GSK3beta, a mediator of ethanol neurotoxicity
    Xianglin Shi; Fiscal Year: 2013
    ..C3G can cross the blood brain barrier (BBB) and distribute in the brain...
  33. Kynurenic Acid Synthesis in Mouse Brain
    Jianyong Li; Fiscal Year: 2010
    ..Because KYNA cannot pass through the blood brain barrier, it must be produced in the brain...
  34. Novel CNS Target for Sleep-Wake and Psychiatric Disorders
    SCOTT MCNEAR THACHER; Fiscal Year: 2010
    ..Modulation of this transcriptional network could have a major impact in the area of CNS therapeutics. ..
  35. 18F-beta-Endorphin Imaging: Translational Study of an Opioid Peptide Radiotracer
    BRIAN contact REED; Fiscal Year: 2010
    ....
  36. Sepsis Outcomes and Aging: Role of Sleep Disruption and the Blood Brain Barrier
    Mark R Opp; Fiscal Year: 2013
    ..as contributing to chronic inflammation and sepsis outcomes in older adults: sleep fragmentation and blood brain barrier transport...
  37. Viral suppression of CNS autoimmunity
    Stephen A Stohlman; Fiscal Year: 2013
    ..demyelination, but only during viral persistence, after resolution of the infection and re-established blood brain barrier integrity...
  38. Mechanisms and Therapeutics for Rett Syndrome
    Mriganka Sur; Fiscal Year: 2013
    ..Since IGF1 is FDA-approved for clinical use in children with growth failure, this study represents a valid approach for a therapeutic intervention on RTT patients. ..
  39. Angiogenic Response to Hypoxia and Ketosis in Rat Brain
    JOSEPH CHARLES LAMANNA; Fiscal Year: 2012
    ..The ability to alter brain metabolism and produce neuroprotection by dietary adjustments would be a significant new strategy for stroke prevention and recovery. ..
  40. Brain Vascular Studies in Cardiac and Orthopedic Surgery
    David Stump; Fiscal Year: 2013
    ..The MRI analyses will include diffusion-weighted imaging (DWI), spin echo T1, and fast spin echo T2. ..
  41. Auditory Neuroprotection by Small Molecule Agonists of the TrkB Receptor
    Keqiang Ye; Fiscal Year: 2013
    ..These compounds readily crossed the blood brain barrier and into the cochlea. They activated TrkB receptors at extremely low concentrations...
  42. Brain Vascular Studies in Cardiac and Orthopedic Surgery
    William Brown; Fiscal Year: 2009
    ..The MRI analyses will include diffusion-weighted imaging (DWI), spin echo T1, and fast spin echo T2. ..
  43. Pathogenesis/Treatment-Inherited Cholesterol Deficiency
    Gordon L Watson; Fiscal Year: 2013
    ..metabolism in the CNS must be treated separately because it is isolated from systemic cholesterol by the blood brain barrier. Gene transfer vector will be injected intrathecally into the cerebrospinal fluid of newborn SLOS mice...
  44. Microanalytical methods for the detection of reactive nitrogen species
    Susan M Lunte; Fiscal Year: 2010
    ..The proposed methodology will make it possible to better elucidate the role of this extremely short lived species in neurodegenerative disease. ..
  45. Vaccines to promote Tc-1-based targeting of tumor stroma
    Walter J Storkus; Fiscal Year: 2013
    ..These results may provide the translational inertia to develop vaccine and combinational therapies targeting the tumor stroma that can be applied to patients harboring any type of vascularized cancer. ..
  46. Methylmercury exposure, mercury metabolism genotypes, and risk of adult glioma
    Kathleen M Egan; Fiscal Year: 2013
    ..Based on a large, nearly completed case-control study, the proposed pilot investigation may provide new information on a potential environmental risk factor, mechanisms for glioma tumor development, and directions for future study. ..
  47. Effects of Extravasated Serum Proteins on Human Glioblastoma Invasion
    HUNTER REEVE UNDERHILL; Fiscal Year: 2013
    ..The Howard Temin Pathway to Independence Award for Cancer Research (K99/R00) will allow me to complete my post-doctoral training and provide critical support for the transition to a faculty position. ..
  48. Role of ABC efflux transporters in ALS
    Davide Trotti; Fiscal Year: 2013
    ..k.a. ABCG2) at the blood brain barrier (BBB) and blood cerebrospinal fluid (BCSF) barrier...
  49. Orexin Receptor Agonists for the Treatment of Excessive Daytime Sleepiness and Ca
    PAUL STUART HUMPHRIES; Fiscal Year: 2013
    ..Compounds that pass through this critical path will progress into IND-enabling studies and Phase I clinical trials in collaboration with NIH contractors. ..
  50. Astrocyte senescence and HIV-associated neurocognitive disorders
    ELIZABETH PATRICIA CROWE; Fiscal Year: 2013
    ....
  51. MRP4 extrudes cAMP for localized regulation of calcium channel activity
    OLIVIA RUTH BUONARATI; Fiscal Year: 2013
    ..2-associated disorders in the central nervous system, including stroke, depression, anxiety, senility and Alzheimer's disease. ..
  52. Free Radicals and Methamphetamine Abuse
    Maria Cecilia Garibaldi Marcondes; Fiscal Year: 2010
    ..of abuse, exposing users to HIV infection, and potentially facilitating the penetration of virus across the blood brain barrier (BBB) into the brain...
  53. Heat shock proteins in brain ischemia and stroke
    Midori A Yenari; Fiscal Year: 2013
    ..Brain ischemia frequently causes disruption of the blood brain barrier (BBB) leading to brain edema and hemorrhage which can complicate an already catastrophic illness...
  54. Human Blood-Brain Barrier Model for CNS Drug Translation
    Eric V Shusta; Fiscal Year: 2010
    ..Finally, a detailed understanding of EGFR inhibitor permeability and efficacy using the human BBB model along with brain tumor isolates could have substantial impact on the translation of this class of medicines to the clinic. ..
  55. Design of CNS-Permeable Agents for the Treatment of Lipid Storage Diseases
    Scott D Larsen; Fiscal Year: 2010
    ..This proposal will evaluate the feasibility of modifying an established class of small molecule inhibitors of glucosylceramide synthase to achieve potency, specificity and blood brain barrier permeability.
  56. Cell Communication of the Vertebrate Retina
    ROBERT FRANCIS MILLER; Fiscal Year: 2012
    ....
  57. Inhibition of HIV-Induced Synaptodentritic Damage
    Val S Goodfellow; Fiscal Year: 2013
    ..exemplified by CLFB-1134, with excellent in vitro activity in neuron protection assays, excellent blood brain barrier penetration, and satisfactory in vitro safety profiles for CYP450s, hERG and genotoxicity...
  58. Mechanisms of blood-brain barrier disruption by an encephalitic virus
    Katherine R Spindler; Fiscal Year: 2013
    ..This research is ultimately expected to facilitate development of pharmacological approaches to treat both viral encephalitis and other CNS disease. Thus it addresses the NIH mission to reduce the burdens of illness. ..
  59. Targeted DNA Nanoparticles in Brain
    David M Yurek; Fiscal Year: 2010
    ..Successful results from our animal studies could then be translated to human studies using these targeted nanoparticles as a form of non-viral, gene therapy to treat various neurological disorders. ..
  60. Scale-Up from Pilot To High-Throughput Screen for Inhibitors of Aquaporin-4
    Marc F Pelletier; Fiscal Year: 2011
    ..These compounds are currently under development in a Phase II SBIR. With the current screening technologies in place, we are ready to scale-up our drug discovery program to complete a more thorough search for new drug candidates. ..
  61. Young Development of a Novel PET Ligand for Detecting Oxytocin Receptors in Brain
    Larry J Young; Fiscal Year: 2012
    ..The ability of the candidate compounds to penetrate the blood brain barrier and label OTR will be evaluated using transgenic mice expressing the human OTR...
  62. Pre-clinical testing of necrostatin as a potential small molecule for the treatme
    SERGE E PRZEDBORSKI; Fiscal Year: 2012
    ..Herein, we propose to determine the suitability of using this small molecule is a living organism and to demonstrate whether it is protective in an experimental model of ALS. ..
  63. Iron and Mitochondrial Genomics in Neuro-inflammation and HAND: A CHARTER Study
    Asha R Kallianpur; Fiscal Year: 2013
    ....
  64. Therapeutic for Intracerebral Hemorrhage
    Dale Christensen; Fiscal Year: 2009
    ..Cognosci has recently developed novel apoE-based therapeutics that cross the blood brain barrier and exert neuroprotective and anti- inflammatory activities...
  65. Role of chemokines in astro-neuronal activation in cerebral malaria
    Monique Stins; Fiscal Year: 2009
    ..However, the molecular interactions of Pf-IRBC with the blood brain barrier (BBB) endothelial interface and the host responses leading to neurological damage are unclear...
  66. Modulation of Monocarboxylic Acid Transporter Kinetic Function for Stroke Therapy
    JEFFREY PAUL SMITH; Fiscal Year: 2010
    ..because cerebrovascular endothelial cell MCT1 is the sole facilitator of lactic acid transport across the blood brain barrier's cerebrovascular endothelium...
  67. MRI of Acute Vascular Injury and Hemorrhagic Transformation in Ischemic Stroke
    Robert A Knight; Fiscal Year: 2010
    ..e., BBB opening) and both will be functions of the variations in BBB associated proteins and/or brain swelling;and 2) the size of these changes are correlated over time, ROI, and treatment. ..
  68. CNS INJURY AND EDEMA RESEARCH CENTER
    Pak Chan; Fiscal Year: 2007
    ..PhD Oxidative stress generated during cerebral ischemia and reperfusion is a critical event leading to blood brain barrier (BBB) disruption, with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, ..
  69. Blood Brain Barrier Physiology and HIV Dementia
    HOWARD GENDELMAN; Fiscal Year: 2007
    ..factor alpha, among others) that influence monocyte migration into the brain; and 3) by utilizing a blood brain barrier (BBB) and severe combined immune deficiency disease (SCID) mouse model of HIV encephalitis (HIVE) to assess ..
  70. E COLI TRANSLOCATION ACROSS INTESTINAL EPITHELIUM
    Michelle Pietzak; Fiscal Year: 2003
    ..capsular polysaccharide, outer membrane protein A, and S fimbriae using in vitro and in vivo models of the blood brain barrier developed in his lab and (b) identified several novel genes thought to be responsible for invasion of E...
  71. Matrix Metalloproteinase Inhibitors in Stroke
    GARY ALLEN ROSENBERG; Fiscal Year: 2010
    ..The overall goal is to identify lead compounds that are patentable and can be used to obtain IND approval. Promising compounds would be useful for U01- funded clinical trials. ..
  72. PERINATAL METABOLIC STRESS AND BRAIN GLUCOSE TRANSPORT
    SUSAN VANNUCCI; Fiscal Year: 1999
    ..The results of this study should help elucidate the mechanisms by which the immature brain responds to injury and may provide opportunities for intervention in these, and other, perinatal diseases. ..
  73. BLOOD-BRAIN BARRIER IN NORMAL & EXPERIMENTAL BRAIN
    RICHARD BROADWELL; Fiscal Year: 1990
    ..These subjects are important in the subspecialties of neurotrauma, neuro-oncology, cerebrovascular disease, CNS deficiencies, and neuronal regeneration...
  74. Drug Delivery to CNS Endothelial Cells by Targeting Peptide-MHC Complexes
    Ulrich Bickel; Fiscal Year: 2009
    ..The findings can have wide implications for potential protein- or DNA-based therapeutics, which are often hampered by their inability to reach the target tissues. ..
  75. Recombinant siRNA Carriers for Targeted Delivery across the Blood Brain Barrier
    DARIN YALE FURGESON; Fiscal Year: 2010
    ..More problematic is transport across the blood brain barrier (BBB) to effectively treat neurodegenerative pathologies...
  76. VASCULAR PERMEABILITY AND BRAIN EDEMA IN BRAIN ABSCESS
    Warren Lo; Fiscal Year: 1992
    ....
  77. Ultrasound-Mediated Blood-Brain Barrier Permeabilization in Primates
    Steven Gullans; Fiscal Year: 2006
    ..This research aims to develop a method to deliver drugs and other therapies to the brain in a way that is safe and easy to apply. [unreadable] [unreadable]..
  78. CYCLIC PRODRUGS OF OPIOID PEPTIDES
    RONALD BORCHARDT; Fiscal Year: 2007
    ..v. or oral administration. ..