Current research interests
• We study humans at genetic risk for AD, and use transgenic models, and iPSC-based human models of the BBB and brain on a chip to understand how genes that carry risk for sporadic AD (e.g., APOE4, PICALM) affect the cerebrovascular system contributing to dementia, and AD disease onset and progression.
• We are developing cell and gene therapy approaches for AD using i) iPSC-derived human pericytes that express different protective target genes, and/or ii) BBB cell-specific gene delivery to influence neuronal and synaptic functions.
• We study APC biologics and mimetic peptides for white matter stroke, AD and ALS.
• We work on identifying small molecules that influence genes/pathways linked to AD.
• We work on CSF and imaging BBB biomarkers of human cognitive dysfunction.
• Recently, we have initiated studies to understand how gut microbiome influences BBB in relation to neuronal and synaptic functions using transgenic and human iPSC models.
• We initiated program on BBB molecular signatures (snRNAseq, proteome) in health and disease using transgenic and human models, and human tissue studies.
Zlokovic is recognized internationally as a leader in the fields of AD and stroke research. Thomson Reuters and Clarivate Analytics listed Zlokovic as one of “The World’s Most Influential Scientific Minds” for 17 consecutive years (2002-2019) for ranking in 1 % of the most-cited authors in the field of neurosciences and behavioral sciences. He received MetLife Award for Medical Research for “significant contributions to our understanding of Alzheimer’s disease and for bringing us closer to a cure”, Potamkin Prize from the American Academy of Neurology " in recognition of outstanding achievements in research on Alzheimer’s and related neurodegenerative diseases”, Javits Award from NINDS "in recognition of distinguished record of substantial contributions in a field of neurological sciences”, and MERIT Award from NIA "in recognition of sustained contribution to aging and leadership and commitment to the field”. He is a fellow of the AAAS, The European Academy of Sciences, and The Dana Alliance for Brain Initiative. In 2017, 2018, 2019 and 2020, he was asked by the Nobel Assembly at Karolinska Institutet, The Nobel Committee to nominate candidates for the Nobel Prize in Physiology and Medicine. He is also an active entrepreneur and inventor. He co-founded ZZ Biotech, a biotechnology company that is developing treatments for stroke and neurological disorders.
Featured Publications representing interests of the Zlokovic laboratory:
i-10 index: 243; h-index: 99; 43,599 citations (Google Scholar, Jan 2020); complete list in Google Scholar: https://goo.gl/2Npcj2
Nation DA, Sweeney MD, Montagne A, Sagare AP, D’Orazio LM, Pachicano M, Sepehrband F, Nelson AR, Buennagel D, Liu CY, Harrington MG, Benzinger TLS, Fagan AM, Ringman JM, Schneider LS, Morris JC, Chui HC, Law M, Toga AW, Zlokovic BV (2019) Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nature Medicine 25, 270-276.
Nikolakopoulou AM, Montagne A, Kisler K, Dai Z, Wang Y, Huuskonen MT, Sagare AP, Lazic D, Sweeney MD, Kong P, Wang M, Owens NC, Lawson EJ, Xie X, Zhao Z, Zlokovic BV (2019) Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss. Nature Neuroscience 22, 1089–1098.
Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2019) Blood-Brain Barrier: From Physiology to Disease and Back. Physiological Reviews 99, 21-78.
Lazic D, Sagare AP, Nikolakopoulou AM, Griffin JH, Vassar R, Zlokovic BV (2019) 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice. Journal of Experimental Medicine 216(2), 279-293.
Lyden P, Pryor KE, Coffey CS, Cudkowicz M, …Davis TP, Toga AW, Griffin JH, Zlokovic BV, NeuroNEXT Clinical Trials Network NN104 Investigators. (2019) Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke. Annals of Neurology 85(1), 125-136.
Sweeney MD, Kisler K, Montagne A, Toga A, Zlokovic BV (2018) The role of brain vasculature in neurodegenerative disorders. Nature Neuroscience 21(10), 1318-1331
Montagne A, Nikolakopoulou AM, Zhao Z, Sagare AP, Si G, Lazic D, Barnes SR, Daianu M, Ramanathan A, Go A, Lawson EJ, Wang Y, Mack WJ, Thompson PM, Schneider JA, Varkey J, Langen R, Mullins E, Jacobs RE, Zlokovic BV (2018) Pericyte degeneration causes white matter dysfunction in the mouse CNS. Nature Medicine 24(3), 326-337.
Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood-brain barrier breakdown in Alzheimer’s disease and other neurodegenerative disorders. Nature Reviews Neurology 14(3), 133-150.
Kisler K, Lazic D, Sweeney M, Plunkett S, Khatib ME, Vinogradov SA, Boas DA, Sakadzic S, Zlokovic BV (2018) Diverse protocols for in vivo measurements of cerebrovascular hemodynamic responses and tissue oxygen levels and delivery in the mouse brain. Nature Protocols 13(6), 1377-1402.
Sweeney MD, Zlokovic BV (2018) A lymphatic waste-disposal system implicated in Alzheimer’s disease. Nature 560 (7717) 172-174.
Kisler K, Nelson A, Montagne A, Zlokovic BV (2017) Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer’s disease. Nature Reviews Neuroscience 18, 419-434.
Kisler K, Nelson AR, Rege SV, Ramanathan A, Wang Y, Ahuja A, Lazic D, Tsai PS, Zhao Z, Zhou Y, Boas DA, Sakadžic S, Zlokovic BV (2017) Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nature Neuroscience 20, 406-416.
Wang Y, Zhao Z, Rege S, Griffin JH, Goldman SA, Zlokovic BV (2016) 3K3A-APC stimulates post-ischemic neuronal repair by human neural progenitor cells in mice. Nature Medicine 22 (9): 1050-1055.
Sweeney MD, Ayyadurai S, Zlokovic BV (2016) Pericytes of the neurovascular unit: key functions and signaling pathways. Nature Neuroscience 19 (6): 771-783.
Zhao Z, Nelson A, Betsholtz C, Zlokovic BV (2015) Establishment and dysfunction of blood-brain barrier. Cell 163, Nov 19;163(5):1064-78.
Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K, Winkler EA, Ramanathan A, Kanekiyo T, Bu G, Owens NQ, Rege SV, Si G, Ahuja A, Zhu D, Miller CA, Schneider JA, Maeda M, Maeda T, Sugawara T, Ichida JK, Zlokovic BV (2015) Central role for PICALM in amyloid-? blood-brain barrier transcytosis and clearance. Nature Neuroscience 18, 978-987.
Winkler EA, Nishida Y, Sagare AP, Rege SV, Bell RD, Perlmutter D, Sengillo JD, Hillman S, Kong P, Nelson AR, Sullivan JS, Zhao Z, Meiselman HJ, Wendy RB, Soto J, Abel ED, Makshanoff J, Zuniga E, De Vivo DC, Zlokovic BV (2015) GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nature Neuroscience 18, 521-530.
Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, Toga AW, Jacobs RE, Liu CY, Amezcua L, Harrington MG, Chui HC, Law M, Zlokovic BV (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85, 296-302.
Griffin JH, Zlokovic BV, Mosnier LO (2015) Activated Protein C: Biased for Translation. Blood 125 (19), 2898-2907.
Zhao Z and Zlokovic BV (2014) Blood-Brain Barrier: A Dual Life of MFSD2A? Neuron 82, 728–730.
Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong G, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV (2014) Blood-spinal cord barrier disruption contributes to early motor neuron degeneration in ALS model mice. Proceedings of the National Academy of Sciences USA 111(11), E1035-42.
Bell RD, Winkler E, Sagare A, Singh I, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk B, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485, 512-516.
Deane R, Singh I, Sagare A, Bell R, Ross NT, Larue B, Love R, Perry S, Deane RJ, Thiyagarajan M, Zarcone T, Friedman A, Miller BL, Zlokovic BV (2012) A novel multi-modal RAGE-specific inhibitor controls amyloid-beta-mediated brain disorder in mice. Journal of Clinical Investigation 122 (4), 1377-1392.
Winkler E, Bell R, Zlokovic BV (2011) Functions of CNS pericytes in health and disease. Nature Neuroscience 14, 1398-1405.
Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature Reviews Neuroscience 12, 723-738.
Winkler EA, Bell RD, Zlokovic BV (2011) Lack of Smad and Notch Leads to a Fatal Game of Brain Pericyte Hopscotch. Developmental Cell (Cell) 20 (3), 279-281.
Zlokovic BV, Griffin JH (2011) Activated protein C cytoprotective pathways and implications for stroke and neurological disorders. Trends in Neurosciences 34 (4), 1198-2009.
Zlokovic BV (2010) Neurodegeneration and the neurovascular unit. Nature Medicine 16(12), 1370-71.
Bell RD, Winkler EA, Sagare A, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and the neuronal phenotype in the adult brain and during brain aging. Neuron 68, 409-427.
Zhu D, Wang Y, Singh I, Bell RD, Deane R, Zhong Z, Sagare A, Winkler EA, Zlokovic BV (2010) Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. Blood 115, 4963-4972.
Bell RD , Deane R, Chow N, Long X, Sagare A, Singh I, Streb JW, Guo H, Rubio A, Van Nostrand W, Miano JP, Zlokovic BV (2009) SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nature Cell Biology 11(2), 143-153.
Zhong Z, Ilieva H, Hallagan L, Bell R, Singh I, Paquette N, Thiyagarajan M, Deane R, Fernandez JA, Lane S, Zlokovic AB, Liu T, Griffin JH, Chow N, Castellino F, Stojanovic K, Cleveland DW, Zlokovic BV (2009) Activated protein C slows ALS-like disease by transcrptionally inhibiting SOD1 in motor neurons and microglial cells. Journal of Clinical Investigation 119(11), 3437-3440.
Deane R, Sagare A, Hamm K, Parisi M, Lane S, Finn MB, Holtzman DM, Zlokovic BV (2008) Apolipoprotein E isoform-specific disruption of Alzheimer’s amyloid ?-peptide clearance from mouse brain. Journal of Clinical Investigation 118(12), 4002-4013.
Zhong Z, Deane R, Zarina A, Parisi M, Shapovalov Y, 0’Banion K, Stojanovic K, Sagare A, Boillee S, Cleveland DW, Zlokovic BV (2008) ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nature Neuroscience 11(4), 420-422.
Zlokovic BV (2008) Blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 57, 178-201.
Sagare A, Deane R, Bell RD, Johnson B, Hamm K, Pendu R, Marky A, Lenting PJ, Wu Z, Zarcone T, Goate A, Mayo K, Pelmutter D, Coma M, Zhong Z, Zlokovic BV (2007) Clearance of amyloid-beta by circulating lipoprotein receptors. Nature Medicine 13 (9), 1029-1031.
Chow N, Bell RD, Deane R, Streb JW, Chen J, Brooks A, Van Nostrand W, Miano JM, Zlokovic BV (2007). Serum response factor and myocardin mediate cerebral arterial hypercontractility and blood flow dysregulation in Alzheimer’s phenotype. Proceedings of the National Academy of Sciences USA 104, 823-828.
Mosnier L, Zlokovic BV, Griffin JH (2007) The cellular protein C pathway. Blood 109(8), 161-172.
Cheng T, Petraglia A, Li Z, Meedakshisudaram T, Wu Z, Zhong Z, Liu D, Maggirwar SB, Deane R, Fernandez J, LaRue B, Griffin J, Chopp M, Zlokovic BV (2006) Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage. Nature Medicine 12 (11), 1278-1285.
Zlokovic BV (2006) Remodeling after stroke. Nature Medicine 12 (4) 390-391.
Wu Z, Guo H, Chow N, Sallstrom J, Bell RD, Deane R, Brooks A, Kanagala S, Rubio A, Sagare A, Liu D, Li F, Armstrong D, Gasiewicz T, Zidovetski R, Song H, Hofman F, Zlokovic BV (2005) Role of MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nature Medicine 11(9), 959-965.
Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends in Neurosciences 28, 202-208.
Deane R, Wu Z, Davis J, Yan SD, Hamm K, Sagare A, Xu F, Spijkers P, Lenting PJ, Van Nostrand WE, Zlokovic BV (2004) LRP-amyloid-beta interaction mediates differential brain efflux of Abeta isoforms. Neuron 43, 33-44.
Liu D, Cheng T, Guo H, Fernandez AJ, Griffin JH, Song X, Zlokovic BV (2004) Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C. Nature Medicine 10, (12), 1379-1383.
Guo H, Liu D, Gelbard H, Cheng T, Fernandez JA, Insalaca R, Griffin JH, Zlokovic BV (2004) Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron 41, 563-572.
Deane R, Yan SD, Kumar R, Jovanovic S, LaRue B, Welch D, Maness L, Yu J, Zhu H, Ghiso J, Frangione B, Schmidt AM, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic BV (2003) RAGE mediates amyloid-ß peptide transport across the blood-brain barrier and accumulation in brain. Nature Medicine 9(7), 907-913.
Cheng T, Liu D, Fernández JA, Griffin JH, Castellino F, Rosen E, Fukudome K, Zlokovic BV (2003) Activated protein C blocks P53-mediated apoptosis in ischemic human brain endothelium and is neuroportective. Nature Medicine 9, 338-342.
Domotor E, Benzakour O, Griffin JH, Yule D, Fukudome K, Zlokovic BV (2003) Activated protein C alters cytosolic Ca2+ flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease-activated receptor-1. Blood 101, 4797-4801.
Shibata M, Subramanyan RK, Amar A, Fernandez J, Griffin J, Zlokovic BV (2001) Anti-inflammatory, antithrombotic and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke with cerebrovascular thrombosis. Circulation 103, 1799-1805.
Shibata M, Yamada S, Kumar RS, Calero M, Bading B, Frangione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, Zlokovic BV (2000) Clearance of Alzheimer’s amyloid-ß1-40 peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. Journal of Clinical Investigation 106(12), 1489-1499.
Zlokovic BV, Shinya Y, Holtzman D, Ghiso J, Frangione B (2000) Clearance of amyloid ß-peptide from brain: transport or metabolism? Nature Medicine 6, 718-719.
Mackic JB, Stins M, McComb JG, Calero M, Ghiso J, Kim KS, Yan SD, Stern D, Schmidt AM, Frangione B, Zlokovic BV (1998) Human blood-brain barrier receptors for Alzheimer's amyloid-? 1-40: Asymmetrical binding, endocytosis and transcytosis at the apical side of brain microvascular endothelial cell monolayer. Journal of Clinical Investigation 102, 734-743.
Zlokovic BV, Martel CL, Matsubara E, McComb JG, Zheng G, McCluskey RT, Frangione B, Ghiso J (1996) Glycoprotein 330/megalin: Porbable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer's Disease amyloid-? at the blood-brain and blood-cerebrospinal fluid barriers. Proceedings of the National Academy of Sciences USA 93, 4229-4236.
APOE4 Accelerates Development of Dementia After Stroke: Is There a Role for Cerebrovascular Dysfunction? Stroke. 2020 Mar; 51(3):699-700.. View in PubMed
Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction Nat Med. 2019 02; 25(2):270-276. . View in PubMed
3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice J Exp Med. 2019 02 04; 216(2):279-293. . View in PubMed
Blood-Brain Barrier: From Physiology to Disease and Back Physiol Rev. 2019 01 01; 99(1):21-78. . View in PubMed
A lymphatic waste-disposal system implicated in Alzheimer's disease Nature. 2018 08; 560(7717):172-174. . View in PubMed
Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders Nat Rev Neurol. 2018 03; 14(3):133-150. . View in PubMed
Neuropharmacology. 2018 05 15; 134(Pt B):293-301. . View in PubMed
Activated protein C, protease activated receptor 1, and neuroprotection Blood. 2018 07 12; 132(2):159-169. . View in PubMed
Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-ß42 by LRP1-dependent apolipoprotein E isoform-specific mechanism Mol Neurodegener. 2018 10 19; 13(1):57. . View in PubMed
Alzheimer's disease: A matter of blood-brain barrier dysfunction? J Exp Med. 2017 Nov 06; 214(11):3151-3169.. View in PubMed
Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease Nat Rev Neurosci. 2017 07; 18(7):419-434. . View in PubMed
Activated protein C promotes neuroprotection: mechanisms and translation to the clinic Thromb Res. 2016 May; 141 Suppl 2:S62-4. . View in PubMed
Brain imaging of neurovascular dysfunction in Alzheimer's disease Acta Neuropathol. 2016 May; 131(5):687-707. . View in PubMed
Clearance systems in the brain--implications for Alzheimer diseaser Nat Rev Neurol. 2016 Apr; 12(4):248. . View in PubMed
2016 Scientific Sessions Sol Sherry Distinguished Lecturer in Thrombosis: Thrombotic Stroke: Neuroprotective Therapy by Recombinant-Activated Protein C Arterioscler Thromb Vasc Biol. 2016 11; 36(11):2143-2151. . View in PubMed
3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice Nat Med. 2016 09; 22(9):1050-5. . View in PubMed
Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease J Cereb Blood Flow Metab. 2016 Jan; 36(1):216-27. . View in PubMed
Blood-Brain Barrier Permeability and Gadolinium: Benefits and Potential Pitfalls in Research JAMA Neurol. 2016 Jan; 73(1):13-4. . View in PubMed
Consensus statement for diagnosis of subcortical small vessel disease J Cereb Blood Flow Metab. 2016 Jan; 36(1):6-25. . View in PubMed
Clearance systems in the brain-implications for Alzheimer disease Nat Rev Neurol. 2015 Aug; 11(8):457-70. . View in PubMed
Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease J Cereb Blood Flow Metab. 2015 Jul; 35(7):1055-68. . View in PubMed
Central role for PICALM in amyloid-ß blood-brain barrier transcytosis and clearance Nat Neurosci. 2015 Jul; 18(7):978-87. . View in PubMed
Activated protein C: biased for translation Blood. 2015 May 07; 125(19):2898-907. . View in PubMed
7T Multi-shell Hybrid Diffusion Imaging (HYDI) for Mapping Brain Connectivity in Mice Proc SPIE Int Soc Opt Eng. 2015 Mar 20; 9413. . View in PubMed
Blood-brain barrier breakdown in the aging human hippocampus Neuron. 2015 Jan 21; 85(2):296-302. . View in PubMed
Combined neurothrombectomy or thrombolysis with adjunctive delivery of 3K3A-activated protein C in acute ischemic stroke Front Cell Neurosci. 2015; 9:344. . View in PubMed
Cytoprotective-selective activated protein C therapy for ischaemic stroke Thromb Haemost. 2014 Nov; 112(5):883-92. . View in PubMed
Blood-brain barrier: a dual life of MFSD2A? Neuron. 2014 May 21; 82(4):728-30.. View in PubMed
Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice Proc Natl Acad Sci U S A. 2014 Mar 18; 111(11):E1035-42. . View in PubMed
Activated protein C analog protects from ischemic stroke and extends the therapeutic window of tissue-type plasminogen activator in aged female mice and hypertensive rats Stroke. 2013 Dec; 44(12):3529-36. . View in PubMed
A lipoprotein receptor cluster IV mutant preferentially binds amyloid-ß and regulates its clearance from the mouse brain J Biol Chem. 2013 May 24; 288(21):15154-66. . View in PubMed
Deficiency in mural vascular cells coincides with blood-brain barrier disruption in Alzheimer's disease Brain Pathol. 2013 May; 23(3):303-10. . View in PubMed
Activated protein C analog promotes neurogenesis and improves neurological outcome after focal ischemic stroke in mice via protease activated receptor 1 Brain Res. 2013 Apr 24; 1507:97-104. . View in PubMed
An activated protein C analog stimulates neuronal production by human neural progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway J Neurosci. 2013 Apr 03; 33(14):6181-90. . View in PubMed
A gliovascular idea for the white matter repair? J Neurochem. 2013 Apr; 125(2):172-4.. View in PubMed
Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease JAMA Neurol. 2013 Apr; 70(4):440-4. . View in PubMed
Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis Acta Neuropathol. 2013 Jan; 125(1):111-20. . View in PubMed
Blood-spinal cord barrier pericyte reductions contribute to increased capillary permeability J Cereb Blood Flow Metab. 2012 Oct; 32(10):1841-52. . View in PubMed
An activated protein C analog with reduced anticoagulant activity extends the therapeutic window of tissue plasminogen activator for ischemic stroke in rodents Stroke. 2012 Sep; 43(9):2444-9. . View in PubMed
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A Nature. 2012 May 16; 485(7399):512-6. . View in PubMed
A multimodal RAGE-specific inhibitor reduces amyloid ß-mediated brain disorder in a mouse model of Alzheimer disease J Clin Invest. 2012 Apr; 122(4):1377-92. . View in PubMed
Central nervous system pericytes in health and disease Nat Neurosci. 2011 Oct 26; 14(11):1398-1405. . View in PubMed
Cytoprotective protein C pathways and implications for stroke and neurological disorders Trends Neurosci. 2011 Apr; 34(4):198-209. . View in PubMed
Activated protein C analog with reduced anticoagulant activity improves functional recovery and reduces bleeding risk following controlled cortical impact Brain Res. 2010 Aug 06; 1347:125-31. . View in PubMed
Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact Neurosurgery. 2010 Jan; 66(1):165-71; discussion 171-2. . View in PubMed
Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells J Clin Invest. 2009 Nov; 119(11):3437-49. . View in PubMed
Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease CNS Neurol Disord Drug Targets. 2009 Mar; 8(1):16-30. . View in PubMed
apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain J Clin Invest. 2008 Dec; 118(12):4002-13. . View in PubMed
Activated protein C promotes neovascularization and neurogenesis in postischemic brain via protease-activated receptor 1 J Neurosci. 2008 Nov 26; 28(48):12788-97. . View in PubMed
ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration Nat Neurosci. 2008 Apr; 11(4):420-2. . View in PubMed
Coupling of angiogenesis and neurogenesis in cultured endothelial cells and neural progenitor cells after stroke J Cereb Blood Flow Metab. 2008 Apr; 28(4):764-71. . View in PubMed
Clearance of amyloid-beta by circulating lipoprotein receptors Nat Med. 2007 Sep; 13(9):1029-31. . View in PubMed
Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage Nat Med. 2006 Nov; 12(11):1278-85. . View in PubMed
Clearing amyloid through the blood-brain barrier J Neurochem. 2004 May; 89(4):807-11. . View in PubMed
Activated protein C and ischemic stroke Crit Care Med. 2004 May; 32(5 Suppl):S247-53. . View in PubMed
Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3 Neuron. 2004 Feb 19; 41(4):563-72. . View in PubMed
Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain J Neurochem. 2004 Feb; 88(4):813-20. . View in PubMed
A simple method for isolation and characterization of mouse brain microvascular endothelial cells J Neurosci Methods. 2003 Nov 30; 130(1):53-63. . View in PubMed
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 Blood. 2003 Jun 15; 101(12):4797-801. . View in PubMed
Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective Nat Med. 2003 Mar; 9(3):338-42. . View in PubMed
Current treatments and therapeutic targets in Alzheimer's disease Adv Drug Deliv Rev. 2002 Dec 07; 54(12):1533-7. . View in PubMed
Activated protein C: potential therapy for severe sepsis, thrombosis, and stroke Semin Hematol. 2002 Jul; 39(3):197-205. . View in PubMed
Brain clearance of Alzheimer's amyloid-beta40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy J Drug Target. 2002 Jun; 10(4):359-68. . View in PubMed
Circulating amyloid-beta peptide crosses the blood-brain barrier in aged monkeys and contributes to Alzheimer's disease lesions Vascul Pharmacol. 2002 Jun; 38(6):303-13. . View in PubMed
Anti-inflammatory, antithrombotic, and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke Circulation. 2001 Apr 03; 103(13):1799-805. . View in PubMed
Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier J Clin Invest. 2000 Dec; 106(12):1489-99. . View in PubMed
beta-amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1 Am J Physiol Cell Physiol. 2000 Dec; 279(6):C1772-81. . View in PubMed
Apolipoprotein J (clusterin) and Alzheimer's disease Microsc Res Tech. 2000 Aug 15; 50(4):305-15. . View in PubMed
Cellular cofactors potentiating induction of stress and cytotoxicity by amyloid beta-peptide Biochim Biophys Acta. 2000 Jul 26; 1502(1):145-57. . View in PubMed
Clearance of amyloid beta-peptide from brain: transport or metabolism? Nat Med. 2000 Jul; 6(7):718-9.. View in PubMed
Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model J Cereb Blood Flow Metab. 2000 Jun; 20(6):998-1009. . View in PubMed
Cereport (RMP-7) increases the permeability of human brain microvascular endothelial cell monolayers Pharm Res. 1999 Sep; 16(9):1360-5. . View in PubMed
Corneal transport of circulating glutathione in normal and galactosemic guinea pigs Cornea. 1999 May; 18(3):321-7. . View in PubMed
Detection of brain tumor invasion and micrometastasis in vivo by expression of enhanced green fluorescent protein Neurosurgery. 1998 Dec; 43(6):1437-42; discussion 1442-3. . View in PubMed
Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer's amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy J Neurochem. 1998 Jan; 70(1):210-5. . View in PubMed
Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury J Cereb Blood Flow Metab. 1998 Jan; 18(1):52-8. . View in PubMed
Attenuation of brain injury and reduction of neuron-specific enolase by nicardipine in systemic circulation following focal ischemia and reperfusion in a rat model J Neurosurg. 1997 Nov; 87(5):731-7. . View in PubMed
Antithrombotic, procoagulant, and fibrinolytic mechanisms in cerebral circulation: implications for brain injury and protection Neurosurg Focus. 1997 Jun 15; 2(6):e5. . View in PubMed
Cellular and molecular neurosurgery: pathways from concept to reality--part II: vector systems and delivery methodologies for gene therapy of the central nervous system Neurosurgery. 1997 Apr; 40(4):805-12; discussion 812-3. . View in PubMed
Cellular and molecular neurosurgery: pathways from concept to reality--part I: target disorders and concept approaches to gene therapy of the central nervous system Neurosurgery. 1997 Apr; 40(4):789-803; discussion 803-4. . View in PubMed
Chronic nicotine treatment enhances focal ischemic brain injury and depletes free pool of brain microvascular tissue plasminogen activator in rats J Cereb Blood Flow Metab. 1997 Feb; 17(2):136-46. . View in PubMed
Can blood-brain barrier play a role in the development of cerebral amyloidosis and Alzheimer's disease pathology Neurobiol Dis. 1997; 4(1):23-6. . View in PubMed
Brain capillary tissue plasminogen activator in a diabetes stroke model Stroke. 1996 Apr; 27(4):712-9. . View in PubMed
Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid beta in guinea pigs Neurosci Lett. 1996 Mar 15; 206(2-3):157-60. . View in PubMed
Cellular uptake and transport of methylprednisolone at the blood-brain barrier Neurosurgery. 1996 Feb; 38(2):348-54. . View in PubMed
Cerebrovascular transport of Alzheimer's amyloid beta and apolipoproteins J and E: possible anti-amyloidogenic role of the blood-brain barrier Life Sci. 1996; 59(18):1483-97. . View in PubMed
Cerebrovascular permeability to peptides: manipulations of transport systems at the blood-brain barrier Pharm Res. 1995 Oct; 12(10):1395-406. . View in PubMed
Brain uptake of circulating apolipoproteins J and E complexed to Alzheimer's amyloid beta Biochem Biophys Res Commun. 1994 Dec 15; 205(2):1431-7. . View in PubMed
Blood-to-lens transport of reduced glutathione in an in situ perfused guinea-pig eye Exp Eye Res. 1994 Oct; 59(4):487-96. . View in PubMed
Blood-brain barrier transport of circulating Alzheimer's amyloid beta Biochem Biophys Res Commun. 1993 Dec 30; 197(3):1034-40. . View in PubMed
Blood-brain transport of vasopressin Adv Exp Med Biol. 1993; 331:143-7. . View in PubMed
A simple technique to determine glutathione (GSH) levels and synthesis in ocular tissues as GSH-bimane adduct: application to normal and galactosemic guinea-pigs Exp Eye Res. 1993 Jan; 56(1):45-50. . View in PubMed
An in situ perfused guinea-pig eye model for blood-ocular transport studies: application to amino acids Exp Eye Res. 1992 Mar; 54(3):471-7. . View in PubMed
A saturable mechanism for transport of immunoglobulin G across the blood-brain barrier of the guinea pig Exp Neurol. 1990 Mar; 107(3):263-70. . View in PubMed
Circulating neuroactive peptides and the blood-brain and blood-cerebrospinal fluid barriers Endocrinol Exp. 1990 Mar; 24(1-2):9-17. . View in PubMed
Comparison between blood and saline perfusion on the uptake of amino acids by choroid plexus of the sheep Endocrinol Exp. 1990 Mar; 24(1-2):29-36. . View in PubMed
Chronic amphetamine intoxication and the blood-brain barrier permeability to inert polar molecules studied in the vascularly perfused guinea pig brain J Neurol Sci. 1989 Dec; 94(1-3):41-50. . View in PubMed
Blood-brain barrier permeability changes during acute allergic encephalomyelitis induced in the guinea pig Metab Brain Dis. 1989 Mar; 4(1):33-40. . View in PubMed
Blood-brain barrier permeability to leucine-enkephalin, D-alanine2-D-leucine5-enkephalin and their N-terminal amino acid (tyrosine) Brain Res. 1985 Jun 10; 336(1):125-32. . View in PubMed
Blood-brain barrier permeability to dipeptides and their constituent amino acids Brain Res. 1983 Jul 18; 271(1):65-71. . View in PubMed