Berislav Zlokovic

Summary

Affiliation: University of Rochester
Country: USA

Publications

  1. ncbi Brain clearance of Alzheimer's amyloid-beta40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy
    James R Bading
    Department of Radiology, USC School of Medicine, Los Angeles, CA 90033, USA
    J Drug Target 10:359-68. 2002
  2. pmc Blood-spinal cord barrier pericyte reductions contribute to increased capillary permeability
    Ethan A Winkler
    Department of Physiology and Biophysics, University of Southern California, Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Los Angeles, California 90089, USA
    J Cereb Blood Flow Metab 32:1841-52. 2012
  3. 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
  4. ncbi Neurovascular pathways and Alzheimer amyloid beta-peptide
    Berislav V Zlokovic
    Frank R Smith Laboratories for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Brain Pathol 15:78-83. 2005
  5. ncbi Neurovascular mechanisms of Alzheimer's neurodegeneration
    Berislav V Zlokovic
    Frank P Smith Laboratories for Neuroscience and Neurological Surgery Research, Department of Neurological Surgery and Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Trends Neurosci 28:202-8. 2005
  6. pmc Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway
    Huang Guo
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery and Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Mol Neurodegener 6:13. 2011
  7. pmc New therapeutic targets in the neurovascular pathway in Alzheimer's disease
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, Departments of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA
    Neurotherapeutics 5:409-14. 2008
  8. pmc Cytoprotective protein C pathways and implications for stroke and neurological disorders
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurological Surgery, University of Rochester Medical Center, Rochester, New York, USA
    Trends Neurosci 34:198-209. 2011
  9. pmc Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling
    Ethan A Winkler
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery, University of Rochester, Rochester, NY, USA
    Mol Neurodegener 5:32. 2010
  10. ncbi Functional recovery after embolic stroke in rodents by activated protein C
    Berislav V Zlokovic
    Department of Neurosurgery and Division of Neurovascular Biology, Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Ann Neurol 58:474-7. 2005

Research Grants

  1. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2003
  2. Alzheimer's ABeta, Apolipoproteins & Blood-Brain Barrier
    Berislav Zlokovic; Fiscal Year: 2001
  3. Alzheimer's Abeta, apolipoproteins and blood-brain barrier
    Berislav Zlokovic; Fiscal Year: 2007
  4. Protein S: Neurovascular Protection in Stroke
    Berislav Zlokovic; Fiscal Year: 2007
  5. Cerebrovascular beta-Amyloidosis: A-beta CNS Transport Pathways
    Berislav Zlokovic; Fiscal Year: 2007
  6. Protein S: Neurovascular Protection in Stroke
    Berislav Zlokovic; Fiscal Year: 2009
  7. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2009
  8. Protein S: Neurovascular Protection in Stroke
    Berislav V Zlokovic; Fiscal Year: 2010
  9. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2007
  10. Protein S: Neurovascular Protection in Stroke
    Berislav Zlokovic; Fiscal Year: 2006

Collaborators

Detail Information

Publications63

  1. ncbi Brain clearance of Alzheimer's amyloid-beta40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy
    James R Bading
    Department of Radiology, USC School of Medicine, Los Angeles, CA 90033, USA
    J Drug Target 10:359-68. 2002
    ..Thus, vascular clearance plays an important role in reducing Abeta levels in the squirrel monkey brain and impaired Abeta40 elimination across the BBB may contribute to the development of CAA...
  2. pmc Blood-spinal cord barrier pericyte reductions contribute to increased capillary permeability
    Ethan A Winkler
    Department of Physiology and Biophysics, University of Southern California, Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Los Angeles, California 90089, USA
    J Cereb Blood Flow Metab 32:1841-52. 2012
    ..Regional reductions in spinal cord pericytes may provide a cellular basis for heightened spinal cord barrier capillary permeability and motor neuron loss...
  3. 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...
  4. ncbi Neurovascular pathways and Alzheimer amyloid beta-peptide
    Berislav V Zlokovic
    Frank R Smith Laboratories for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Brain Pathol 15:78-83. 2005
    ..We suggest that there is a link between neurovascular dysfunction and elevated brain Abeta which provides a new scenario for therapeutic interventions to control Alzheimer mental deterioration...
  5. ncbi Neurovascular mechanisms of Alzheimer's neurodegeneration
    Berislav V Zlokovic
    Frank P Smith Laboratories for Neuroscience and Neurological Surgery Research, Department of Neurological Surgery and Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Trends Neurosci 28:202-8. 2005
    ....
  6. pmc Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway
    Huang Guo
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery and Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Mol Neurodegener 6:13. 2011
    ..abstract:..
  7. pmc New therapeutic targets in the neurovascular pathway in Alzheimer's disease
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, Departments of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA
    Neurotherapeutics 5:409-14. 2008
    ..g., mesenchyme homeobox gene 2 and myocardin) are also discussed...
  8. pmc Cytoprotective protein C pathways and implications for stroke and neurological disorders
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurological Surgery, University of Rochester Medical Center, Rochester, New York, USA
    Trends Neurosci 34:198-209. 2011
    ....
  9. pmc Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling
    Ethan A Winkler
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery, University of Rochester, Rochester, NY, USA
    Mol Neurodegener 5:32. 2010
    ....
  10. ncbi Functional recovery after embolic stroke in rodents by activated protein C
    Berislav V Zlokovic
    Department of Neurosurgery and Division of Neurovascular Biology, Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Ann Neurol 58:474-7. 2005
    ..In contrast, tissue plasminogen activator alone was not protective. Thus, activated protein C may be useful as a new stand-alone therapy for clinical stroke and to extend the time window of thrombolytic therapy...
  11. pmc Low-density lipoprotein receptor-related protein-1: a serial clearance homeostatic mechanism controlling Alzheimer's amyloid β-peptide elimination from the brain
    Berislav V Zlokovic
    Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurochem 115:1077-89. 2010
    ..We suggest that LRP1 has a critical role in AD pathogenesis and is an important therapeutic target in AD...
  12. ncbi Vascular disorder in Alzheimer's disease: role in pathogenesis of dementia and therapeutic targets
    Berislav V Zlokovic
    Frank P Smith Laboratories for Neurosurgery and Division of Neurovascular Biology, Center for Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Adv Drug Deliv Rev 54:1553-9. 2002
    ..In addition, vascularly-based therapeutic strategies to limit the development of beta-amyloidosis and to remove amyloid and plaques from the CNS of AD individuals are discussed...
  13. ncbi Current treatments and therapeutic targets in Alzheimer's disease
    Berislav V Zlokovic
    Department of Neurological Surgery, Division of Neurovascular Biology, University of Rochester Medical Center, NY 14642, USA
    Adv Drug Deliv Rev 54:1533-7. 2002
  14. 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...
  15. ncbi Method for measurement of the blood-brain barrier permeability in the perfused mouse brain: application to amyloid-beta peptide in wild type and Alzheimer's Tg2576 mice
    Barbra LaRue
    Department of Neurosurgery, Frank P Smith Neurosurgical Research Laboratory, Center of Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 670, Rochester, NY 14642, USA
    J Neurosci Methods 138:233-42. 2004
    ....
  16. ncbi RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier
    Rashid Deane
    Frank P Smith Laboratories for Neuroscience and Neurosurgical Research, Department of Neurological Surgery and Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, NY, USA
    Stroke 35:2628-31. 2004
    ....
  17. pmc Activated protein C promotes neovascularization and neurogenesis in postischemic brain via protease-activated receptor 1
    Meenakshisundaram Thiyagarajan
    Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurosci 28:12788-97. 2008
    ..e., neovascularization and neurogenesis), suggesting a significant extension of the therapeutic window for APC intervention in postischemic brain...
  18. pmc Activated protein C analog with reduced anticoagulant activity improves functional recovery and reduces bleeding risk following controlled cortical impact
    Corey T Walker
    Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Arthur Kornberg Medical Research Building, 601 Elmwood Ave, Box 670, Rochester, New York 14642, USA
    Brain Res 1347:125-31. 2010
    ..Thus, compared to wt-APC, 3K3A-APC is more efficacious and safer therapy for TBI with no risk for intracerebral hemorrhage...
  19. pmc Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact
    Anthony L Petraglia
    Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA
    Neurosurgery 66:165-71; discussion 171-2. 2010
    ..We used a controlled cortical impact (CCI) in mice to determine the effects of APC on neuroprotection and angiogenesis and neurogenesis after traumatic brain injury (TBI)...
  20. ncbi RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain
    Rashid Deane
    Frank P Smith Laboratories for Neurosurgery, Department of Neurosurgery and Division of Neurovascular Biology, Center for Aging and Developmental Biology, University of Rochester Medical Center, Rochester, New York 14642, USA
    Nat Med 9:907-13. 2003
    ..These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis...
  21. pmc SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells
    Robert D Bell
    Center for Neurodegenerative and Vascular Brain Disorders, Arthur Kornberg Medical Research Building, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA
    Nat Cell Biol 11:143-53. 2009
    ..Hypoxia stimulated SRF/MYOCD expression in human cerebral VSMCs and in animal models of AD. We suggest that SRF and MYOCD function as a transcriptional switch, controlling Abeta cerebrovascular clearance and progression of AD...
  22. ncbi Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease
    Rashid Deane
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Curr Alzheimer Res 4:191-7. 2007
    ..These findings provide insights into new pathogenic pathways for the vascular dysfunction in AD and point to new therapeutic targets for AD...
  23. pmc Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain
    Rashid Deane
    Frank P Smith Neurosurgical Research Laboratory, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurochem 88:813-20. 2004
    ....
  24. ncbi Circulating amyloid-beta peptide crosses the blood-brain barrier in aged monkeys and contributes to Alzheimer's disease lesions
    Jasmina B Mackic
    Department of Neurological Surgery, USC School of Medicine, Los Angeles, CA 90033, USA
    Vascul Pharmacol 38:303-13. 2002
    ..Negligible capillary binding, rapid systemic and brain degradation, and accelerated body elimination of blood-borne A beta, may prevent the development of CAA in rhesus in contrast to squirrel monkeys...
  25. pmc Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease
    Robert D Bell
    Arthur Kornberg Medical Research Building, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 670, Rochester, New York 14642, USA
    Acta Neuropathol 118:103-13. 2009
    ..The data reviewed here support an essential role of neurovascular and BBB mechanisms in contributing to both, onset and progression of AD...
  26. pmc Clearance of amyloid-beta by circulating lipoprotein receptors
    Abhay Sagare
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA
    Nat Med 13:1029-31. 2007
    ....
  27. pmc Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells
    Zhihui Zhong
    Center for Neurodegenerative and Vascular Brain Disorders and Department of Neurological Surgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Clin Invest 119:3437-49. 2009
    ..The delayed disease progression in mice after APC administration suggests that this approach may be of benefit to patients with familial, and possibly sporadic, ALS...
  28. pmc ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
    Zhihui Zhong
    Center for Neurodegenerative and Vascular Brain Disorders and Department of Neurosurgery, University of Rochester Medical Center, Kornberg Medical Research Bldg, 601 Elmwood Avenue, Box 670, Rochester, New York 14642, USA
    Nat Neurosci 11:420-2. 2008
    ..SOD1 mutant-mediated endothelial damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, indicating that it was a central contributor to disease initiation...
  29. pmc apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain
    Rashid Deane
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA
    J Clin Invest 118:4002-13. 2008
    ..Thus, apoE isoforms differentially regulate Abeta clearance from the brain, and this might contribute to the effects of APOE genotype on the disease process in both individuals with AD and animal models of AD...
  30. ncbi Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer's disease
    Takahiro Takano
    Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA
    Ann N Y Acad Sci 1097:40-50. 2007
    ....
  31. pmc Methamphetamine causes sustained depression in cerebral blood flow
    Oksana Polesskaya
    Department of Microbiology and Immunology, The University of Rochester Medical Center, 575 Elmwood Avenue, Rochester, NY 14642, USA
    Brain Res 1373:91-100. 2011
    ..These findings show that even a single, acute exposure to MA can result in profound changes in CBF, with potentially deleterious consequences for brain function...
  32. pmc Endothelial protein C receptor-assisted transport of activated protein C across the mouse blood-brain barrier
    Rashid Deane
    Department of Neurosurgery, Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Cereb Blood Flow Metab 29:25-33. 2009
    ..APC brain uptake was reduced by 64% in severely deficient EPCR mice, but not in PAR1 null mice. These data suggest that APC and its variants with reduced anticoagulant activity cross the BBB via EPCR-mediated saturable transport...
  33. ncbi Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3
    Huang Guo
    Socratech Laboratories, Rochester, NY 14620, USA
    Neuron 41:563-72. 2004
    ..Thus, PAR1 and PAR3 mediate anti-apoptotic signaling by APC in neurons, which may suggest novel treatments for neurodegenerative disorders...
  34. ncbi IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor
    Rashid Deane
    Division of Neurovascular Biology, Department of Neurosurgery, Arthur Kornberg Medical Research Building, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurosci 25:11495-503. 2005
    ..Our data suggest that the FcRn pathway at the BBB plays a crucial role in IgG-assisted Abeta removal from the aging brain...
  35. pmc Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system
    Robert D Bell
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Cereb Blood Flow Metab 27:909-18. 2007
    ..7-fold, whereas Abeta42 binding to apoJ enhanced Abeta42 BBB clearance rate by 83%. Thus, Abeta, apoE, and apoJ are cleared from brain by different transport pathways, and apoE and apoJ may critically modify Abeta clearance at the BBB...
  36. ncbi LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms
    Rashid Deane
    Frank P Smith Laboratories for Neuroscience and Neurosurgical Research, Department of Neurosurgery, Arthur Kornberg Medical Research Building, University of Rochester Medical Center, Rochester, NY 14642, USA
    Neuron 43:333-44. 2004
    ..Thus, low-affinity LRP/Abeta interaction and/or Abeta-induced LRP loss at the BBB mediate brain accumulation of neurotoxic Abeta...
  37. ncbi Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective
    Tong Cheng
    Frank P Smith Neurosurgical Research Laboratory, Department of Neurosurgery and Center for Aging and Developmental Biology, Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, New York, USA
    Nat Med 9:338-42. 2003
    ..9). Moreover, the in vivo neuroprotective effects of low-dose mouse APC seemed to be independent of its anti-coagulant activity. Thus, APC protects the brain from ischemic injury by acting directly on brain cells...
  38. pmc Impaired spine formation and learning in GPCR kinase 2 interacting protein-1 (GIT1) knockout mice
    Prashanthi Menon
    Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Brain Res 1317:218-26. 2010
    ..Thus, our data suggest that GIT1 plays an important role in brain in vivo by regulating spine density involved in synaptic plasticity that is required for processes involved in learning...
  39. ncbi Protein S confers neuronal protection during ischemic/hypoxic injury in mice
    Dong Liu
    Frank P Smith Neurosurgical Research Laboratory, Division of Neurovascular Biology, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA
    Circulation 107:1791-6. 2003
    ..Protein S is an antithrombotic factor that also exhibits mitogenic activity. Thus, we hypothesized that protein S may control cerebrovascular thrombosis in stroke and protect brain tissue from ischemic injury...
  40. pmc Neuroprotective activities of activated protein C mutant with reduced anticoagulant activity
    Huang Guo
    Department for Neurosurgery and Neurology, Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, NY 14642, USA
    Eur J Neurosci 29:1119-30. 2009
    ..Thus, 3K3A-APC offers a new approach for safer and more efficacious treatments of neurodegenerative disorders and stroke with APC...
  41. pmc Differential neuroprotection and risk for bleeding from activated protein C with varying degrees of anticoagulant activity
    Yaoming Wang
    Department for Neurosurgery, Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, NY 14642, USA
    Stroke 40:1864-9. 2009
    ..How changes in APC anticoagulant activity influence APC's neuroprotection and risk for bleeding is not clear...
  42. ncbi Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1
    Eszter Domotor
    Frank P Smith Neurological Research Laboratory, Department of Neurosurgery and Division of Neurovascular Biology, University of Rochester Medical Center, NY 14642, USA
    Blood 101:4797-801. 2003
    ..These data suggest that APC regulates [Ca2+]i in human brain endothelium and in HUVECs by binding to EPCR and signaling via PAR-1...
  43. pmc Species-dependent neuroprotection by activated protein C mutants with reduced anticoagulant activity
    Huang Guo
    Department for Neurosurgery and Neurology, Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurochem 109:116-24. 2009
    ..Thus, 3K3A-APC exhibits species-dependent neuroprotection which should be taken into account when designing human trials for ischemic stroke with APC mutants...
  44. ncbi Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C
    Dong Liu
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery and Division of Neurovascular Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, New York 14642, USA
    Nat Med 10:1379-83. 2004
    ..APC blocks tPA's neurovascular toxicity and may add substantially to the effectiveness of tPA therapy for stroke...
  45. pmc Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging
    Robert D Bell
    Department of Neurosurgery and Neurology, University of Rochester Medical Center, Center for Neurodegenerative and Vascular Brain Disorders, Rochester, NY 14642, USA
    Neuron 68:409-27. 2010
    ..Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericyte loss results in a progressive age-dependent vascular-mediated neurodegeneration...
  46. ncbi Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage
    Tong Cheng
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    Nat Med 12:1278-85. 2006
    ..The present findings suggest that APC may improve thrombolytic therapy for stroke, in part, by reducing tPA-mediated hemorrhage...
  47. ncbi Presence and functional activity of the aryl hydrocarbon receptor in isolated murine cerebral vascular endothelial cells and astrocytes
    Carissa R Filbrandt
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Box EHSC, 575 Elmwood Avenue, Rochester, NY 14642, USA
    Neurotoxicology 25:605-16. 2004
    ..Together these data indicate endothelial cells and astrocytes are responsive to TCDD through the AhR-mediated pathway and therefore could be targets of toxicity...
  48. pmc Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding globulin-like region
    Zhihui Zhong
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery and Neurology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Neurosci 30:15521-34. 2010
    ....
  49. pmc Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor
    Donghui Zhu
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery, University of Rochester Medical Center, NY, USA
    Blood 115:4963-72. 2010
    ..Our findings indicate that PS protects the BBB integrity via Tyro3 and S1P(1), suggesting potentially novel treatments for neurovascular dysfunction resulting from hypoxic/ischemic BBB damage...
  50. pmc Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype
    Nienwen Chow
    Socratech Research Laboratories L L C, Department of Neurosurgery, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 104:823-8. 2007
    ..Thus, SRF-MYOCD overexpression in small cerebral arteries appears to initiate independently of Abeta a pathogenic pathway mediating arterial hypercontractility and CBF dysregulation, which are associated with Alzheimer's dementia...
  51. ncbi A simple method for isolation and characterization of mouse brain microvascular endothelial cells
    Zhenhua Wu
    Frank P Smith Laboratories for Neurosurgery, Department of Neurosurgery and Division for Neurovascular Biology, Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, NY 14642, USA
    J Neurosci Methods 130:53-63. 2003
    ....
  52. ncbi Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease
    Zhenhua Wu
    Frank P Smith Laboratories for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Arthur Kornberg Medical Research Building, 601 Elmwood Avenue, Box 670, Rochester, New York 14642, USA
    Nat Med 11:959-65. 2005
    ..The link of MEOX2 to neurovascular dysfunction in Alzheimer disease provides new mechanistic and therapeutic insights into this illness...
  53. ncbi Effect of endothelial cell polarity on beta-amyloid-induced migration of monocytes across normal and AD endothelium
    Ranjit Giri
    Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA
    Am J Physiol Cell Physiol 283:C895-904. 2002
    ..We suggest that Abeta in the AD brain parenchyma or cerebrovasculature initiates cellular signaling that induces PBM to transmigrate across the BBB and accumulate in the brain...
  54. ncbi Recombinant murine-activated protein C is neuroprotective in a murine ischemic stroke model
    Jose A Fernandez
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 30:271-6. 2003
    ..The results imply that murine APC is notably superior to human APC for studies of murine disease models, including thrombosis and ischemic brain injury...
  55. pmc P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model
    John R Cirrito
    Department of Neurology, Washington University Medical School, St Louis, Missouri 63110, USA
    J Clin Invest 115:3285-90. 2005
    ..These data establish a direct link between Pgp and Abeta metabolism in vivo and suggest that Pgp activity at the BBB could affect risk for developing AD as well as provide a novel diagnostic and therapeutic target...
  56. ncbi The promise of protein C
    John H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, MEM180, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 36:211-6. 2006
    ..This review summarizes data from clinical observations, from in vitro studies, and from animal models of focal ischemic injury that provide a compelling rationale for clinical trials of APC for ischemic stroke...
  57. ncbi Remodeling after stroke
    Berislav V Zlokovic
    Nat Med 12:390-1. 2006
  58. ncbi Mechanism of amyloid peptide induced CCR5 expression in monocytes and its inhibition by siRNA for Egr-1
    Ranjit K Giri
    Department of Biochemistry and Molecular Biology, USC Keck School of Medicine, Los Angeles, CA 90033, USA
    Am J Physiol Cell Physiol 289:C264-76. 2005
    ..We suggest that inhibition of Egr-1 by either Egr-1 siRNA or pharmacological agents may reduce activation of monocytes/microglia and possibly ameliorate the inflammation and progression of AD...
  59. ncbi Activated protein C and ischemic stroke
    John H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
    Crit Care Med 32:S247-53. 2004
    ..To summarize clinical observations, animal model experimentation, and in vitro studies that advance knowledge of the protein C system, including activated protein C (APC), in the setting of ischemic stroke...
  60. ncbi Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor
    Judianne Davis
    Department of Medicine, Health Sciences Center, Stony Brook University, Stony Brook, NY 11794 8153, USA
    J Biol Chem 279:20296-306. 2004
    ..These results with Tg-SwDI mice demonstrate that overexpression of human AbetaPP is not required for early-onset and robust accumulation of both vascular and parenchymal Abeta in mouse brain...
  61. ncbi The cytoprotective protein C pathway
    Laurent O Mosnier
    Department of Molecular and Experimental Medicine MEM 180, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA
    Blood 109:3161-72. 2007
    ....
  62. ncbi Endothelial cell protein C receptor: role beyond endothelium?
    Meenakshisundaram Thiyagarajan
    Circ Res 100:155-7. 2007
  63. pmc Coupling of angiogenesis and neurogenesis in cultured endothelial cells and neural progenitor cells after stroke
    Hua Teng
    Department of Neurology, Henry Ford Health System, Detroit, Michigan 48202, USA
    J Cereb Blood Flow Metab 28:764-71. 2008
    ..These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling...

Research Grants24

  1. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2003
    ..Proposed studies will define the role of hypercoagulable state in ischemic stroke and evaluate potential protective vs. deleterious effects of anticoagulant and fibrinolytic therapies for stroke. ..
  2. Alzheimer's ABeta, Apolipoproteins & Blood-Brain Barrier
    Berislav Zlokovic; Fiscal Year: 2001
    ....
  3. Alzheimer's Abeta, apolipoproteins and blood-brain barrier
    Berislav Zlokovic; Fiscal Year: 2007
    ....
  4. Protein S: Neurovascular Protection in Stroke
    Berislav Zlokovic; Fiscal Year: 2007
    ..B. Berk (Rochester) (Tyro 3 RTK-Akt signaling) and Dr. M. Chopp (Henry Ford) (rat stroke model). The results will provide mechanistic insights and test therapeutic agents that may be translated to improved therapy for ischemic stroke. ..
  5. Cerebrovascular beta-Amyloidosis: A-beta CNS Transport Pathways
    Berislav Zlokovic; Fiscal Year: 2007
    ..These studies will provide new therapeutic insights to lower Abeta and prevent development of beta-amyloidosis in AD and familial Abeta-disorders by controlling Abeta CNS transport pathways. ..
  6. Protein S: Neurovascular Protection in Stroke
    Berislav Zlokovic; Fiscal Year: 2009
    ..B. Berk (Rochester) (Tyro 3 RTK-Akt signaling) and Dr. M. Chopp (Henry Ford) (rat stroke model). The results will provide mechanistic insights and test therapeutic agents that may be translated to improved therapy for ischemic stroke. ..
  7. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2009
    ....
  8. Protein S: Neurovascular Protection in Stroke
    Berislav V Zlokovic; Fiscal Year: 2010
    ..B. Berk (Rochester) (Tyro 3 RTK-Akt signaling) and Dr. M. Chopp (Henry Ford) (rat stroke model). The results will provide mechanistic insights and test therapeutic agents that may be translated to improved therapy for ischemic stroke. ..
  9. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2007
    ..abstract_text> ..
  10. Protein S: Neurovascular Protection in Stroke
    Berislav Zlokovic; Fiscal Year: 2006
    ..B. Berk (Rochester) (Tyro 3 RTK-Akt signaling) and Dr. M. Chopp (Henry Ford) (rat stroke model). The results will provide mechanistic insights and test therapeutic agents that may be translated to improved therapy for ischemic stroke. ..
  11. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2001
    ..Proposed studies will define the role of hypercoagulable state in ischemic stroke and evaluate potential protective vs. deleterious effects of anticoagulant and fibrinolytic therapies for stroke. ..
  12. Alzheimer's ABeta, Apolipoproteins & Blood-Brain Barrier
    Berislav Zlokovic; Fiscal Year: 2002
    ....
  13. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2002
    ..Proposed studies will define the role of hypercoagulable state in ischemic stroke and evaluate potential protective vs. deleterious effects of anticoagulant and fibrinolytic therapies for stroke. ..
  14. Alzheimer's ABeta, Apolipoproteins & Blood-Brain Barrier
    Berislav Zlokovic; Fiscal Year: 2003
    ....
  15. AGING BRAIN--CEREBROVASCULAR MECHANISM & AMYLOID BETA
    Berislav Zlokovic; Fiscal Year: 2003
    ..abstract_text> ..
  16. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2004
    ..abstract_text> ..
  17. Alzheimer's ABeta, Apolipoproteins & Blood-Brain Barrier
    Berislav Zlokovic; Fiscal Year: 2004
    ....
  18. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2005
    ..abstract_text> ..
  19. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav Zlokovic; Fiscal Year: 2006
    ..abstract_text> ..
  20. REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS
    Berislav V Zlokovic; Fiscal Year: 2010
    ....