Targeting the neurovascular unit for treatment of neurological disorders

Pharmacology and Therapeutics

Volumn 130, Issue 3, 2011, Pages 239-247

  Vangilder, Reyna L ^a   Rosen, Charles L ^b   Barr, Taura L ^a   Huber, Jason D ^c  

^a WEST VIRGINIA UNIVERSITY SCHOOL OF NURSING   (United States)

^b WEST VIRGINIA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c WEST VIRGINIA UNIVERSITY   (United States)

Author keywords

Alzheimer's disease; Astrocyte; Blood brain barrier; Drug delivery; Stroke

Indexed keywords

ACETYLCHOLINE; CARBIDOPA; DONEPEZIL; LEVODOPA; LIPOSOME; PRODRUG; TETRABENAZINE;

ALZHEIMER DISEASE; ARTICLE; ASTROCYTE; BASEMENT MEMBRANE; BLOOD BRAIN BARRIER; BRAIN CANCER; CENTRAL NERVOUS SYSTEM DISEASE; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG TARGETING; ENDOTHELIUM; EPILEPSY; GENE THERAPY; HOMEOSTASIS; HUNTINGTON CHOREA; MICROGLIA; PARKINSON DISEASE; PERICYTE; PRIORITY JOURNAL; STROKE;

EID: 79955599523     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2010.12.004     Document Type: Review

References (128)

1. N.J. Abbott Astrocyte-endothelial interactions and blood-brain barrier permeability J Anat 200 2002 629 638 (Pubitemid 34823054)
2. C.S. Abraham, N. Harada, M.A. Deli, and M. Niwa Transient forebrain ischemia increases the blood-brain barrier permeability for albumin in stroke-prone spontaneously hypertensive rats Cell Mol Neurobiol 22 2002 455 462 (Pubitemid 36005384)
3. M.I. Alam, S. Beg, A. Samad, S. Baboota, K. Kohli, and J. Ali Strategy for effective brain drug delivery Eur J Pharm Sci 40 2010 385 403
4. G. Allt, and J.G. Lawrenson Pericytes: Cell biology and pathology Cells Tissues Organs 169 2001 1 11 (Pubitemid 32437039)
5. A. Alonso, E. Reinz, M. Fatar, J. Jenne, M.G. Hennerici, and S. Meairs Neurons but not glial cells overexpress ubiquitin in the rat brain following focused ultrasound-induced opening of the blood-brain barrier Neuroscience 169 1 2010 116 124
6. A. Alonso, E. Reinz, J.W. Jenne, M. Fatar, and H. Schmidt-Glenewinkel Reorganization of gap junctions after focused ultrasound blood-brain barrier opening in the rat brain J Cereb Blood Flow Metab 30 7 2010 1394 1402
7. T. Arai, O. Benny, T. Joki, L.G. Menon, M. Machluf, and T. Abe Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes Anticancer Res 30 2010 1057 1064
8. A. Baccarelli, L. Tarantini, R.O. Wright, V. Bollati, A.A. Litonjua, and A. Zanobetti Repetitive element DNA methylation and circulating endothelial and inflammation markers in the VA normative aging study Epigenetics 5 2010
9. W.A. Banks Blood-brain barrier as a regulatory interface Forum Nutr 63 2010 102 110
10. T.L. Barr, Y. Conley, J. Ding, A. Dillman, S. Warach, and A. Singleton Genomic biomarkers and cellular pathways of ischemic stroke by RNA gene expression profiling Neurology 75 2010 1009 1014
11. T.L. Barr, L.L. Latour, K.Y. Lee, T.J. Schaewe, M. Luby, and G.S. Chang Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9 Stroke 41 2010 e123 e128
12. J. Bart, H.J. Groen, N.H. Hendrikse, W.T. van der Graaf, W. Vaalburg, and E.G. de Vries The blood-brain barrier and oncology: New insights into function and modulation Cancer Treat Rev 26 2000 449 462 (Pubitemid 32094862)
13. R.T. Bartus, R.L. Dean III, B. Beer, and A.S. Lippa The cholinergic hypothesis of geriatric memory dysfunction Science 217 1982 408 414
14. D.J. Begley Delivery of therapeutic agents to the central nervous system: The problems and the possibilities Pharmacol Ther 104 2004 29 45 (Pubitemid 39410561)
15. R.D. Bell, and B.V. Zlokovic Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease Acta Neuropathol 118 2009 103 113
16. E.E. Benarroch Astrocyte-neuron interactions: Implications for epilepsy Neurology 73 2009 1323 1327
17. M. Benesch, N. Siegler, K. Hoff, L. Lassay, G. Kropshofer, and H. Muller Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: A multi-institutional retrospective study Anticancer Drugs 20 2009 794 799
18. R.J. Boado, E.K. Hui, J.Z. Lu, Q.H. Zhou, and W.M. Pardridge Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein J Biotechnol 146 2010 84 91
19. G.L. Bowman, J.A. Kaye, M. Moore, D. Waichunas, N.E. Carlson, and J.F. Quinn Blood-brain barrier impairment in Alzheimer disease: Stability and functional significance Neurology 68 2007 1809 1814 (Pubitemid 46791393)
20. T.A. Brooks, B.T. Hawkins, J.D. Huber, R.D. Egleton, and T.P. Davis Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations AJP Heart Circ Physiol 289 2005 H738 H743
21. G. Brousseau, B.P. Rourke, and B. Burke Acetylcholinesterase inhibitors, neuropsychiatric symptoms, and Alzheimer's disease subtypes: An alternate hypothesis to global cognitive enhancement Exp Clin Psychopharmacol 15 2007 546 554 (Pubitemid 351163129)
22. L.P. Cacheaux, S. Ivens, Y. David, A.J. Lakhter, G. Bar-Klein, and M. Shapira Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis J Neurosci 29 2009 8927 8935
23. J. Castillo, J. varez-Sabin, E. Martinez-Vila, J. Montaner, T. Sobrino, and J. Vivancos Inflammation markers and prediction of post-stroke vascular disease recurrence: The MITICO study J Neurol 256 2009 217 224
24. S. Chakraborty, D.K. Kaushik, M. Gupta, and A. Basu Inflammasome signaling at the heart of central nervous system pathology J Neurosci Res 88 2010 1615 1631
25. P.S. Chandra, V.M. Padma, G. Shailesh, B. Chandreshekar, C. Sarkar, and M. Tripathi Hemispherotomy for intractable epilepsy Neurol. India 56 2008 127 132
26. I. Cheong, X. Huang, C. Bettegowda, L.A. Diaz Jr., K.W. Kinzler, and S. Zhou A bacterial protein enhances the release and efficacy of liposomal cancer drugs Science 314 2006 1308 1311 (Pubitemid 44846406)
27. J. Croitoru-Lamoury, G.J. Guillemin, F.D. Boussin, B. Mognetti, L.I. Gigout, and A. Cheret Expression of chemokines and their receptors in human and simian astrocytes: Evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation Glia 41 2003 354 370 (Pubitemid 36314149)
28. E.J. Curran, and J.B. Becker Changes in blood-brain barrier permeability are associated with behavioral and neurochemical indices of recovery following intraventricular adrenal medulla grafts in an animal model of Parkinson's disease Exp Neurol 114 1991 184 192
29. S. Dauchy, F. Miller, P.O. Couraud, R.J. Weaver, B. Weksler, and I.A. Romero Expression and transcriptional regulation of ABC transporters and cytochromes P450 in hCMEC/D3 human cerebral microvascular endothelial cells Biochem Pharmacol 77 2009 897 909
30. M.E. Davis, S.H. Pun, N.C. Bellocq, T.M. Reineke, S.R. Popielarski, and S. Mishra Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers Curr Med Chem 11 2004 179 197 (Pubitemid 38128844)
31. N. Didier, I.A. Romero, C. Creminon, A. Wijkhuisen, J. Grassi, and A. Mabondzo Secretion of interleukin-1beta by astrocytes mediates endothelin-1 and tumour necrosis factor-alpha effects on human brain microvascular endothelial cell permeability J Neurochem 86 2003 246 254 (Pubitemid 36753865)
32. V.A. DiNapoli, J.D. Huber, K. Houser, X. Li, and C.L. Rosen Early disruptions of the blood-brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats Neurobiol Aging 29 2008 753 764 (Pubitemid 351400829)
33. S. Dohgu, F. Takata, A. Yamauchi, S. Nakagawa, T. Egawa, and M. Naito Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production Brain Res 1038 2005 208 215 (Pubitemid 40332685)
34. P. Dore-Duffy, and J.C. Lamanna Physiologic angiodynamics in the brain Antioxid Redox Signal 9 2007 1363 1371 (Pubitemid 47255015)
35. V. Drouet, V. Perrin, R. Hassig, N. Dufour, G. Auregan, and S. Alves Sustained effects of nonallele-specific Huntingtin silencing Ann Neurol 65 3 2009 276 285
36. R.D. Egleton, S.A. Mitchell, J.D. Huber, J. Janders, D. Stropova, and R. Polt Improved bioavailability to the brain of glycosylated Met-enkephalin analogs Brain Res 881 2000 37 46
37. A. Fasano, F. Cadeddu, A. Guidubaldi, C. Piano, F. Soleti, and P. Zinzi The long-term effect of tetrabenazine in the management of Huntington disease Clin Neuropharmacol 31 2008 313 318
38. A. Fournier, R. Oprisiu-Fournier, J.M. Serot, O. Godefroy, J.M. Achard, and S. Faure Prevention of dementia by antihypertensive drugs: How AT1-receptor-blockers and dihydropyridines better prevent dementia in hypertensive patients than thiazides and ACE-inhibitors Expert Rev Neurother 9 2009 1413 1431
39. S. Frank, W. Ondo, S. Fahn, C. Hunter, D. Oakes, and S. Plumb A study of chorea after tetrabenazine withdrawal in patients with Huntington disease Clin Neuropharmacol 31 2008 127 133 (Pubitemid 351787108)
40. Y.J. Gao, and R.R. Ji Chemokines, neuronal-glial interactions, and central processing of neuropathic pain Pharmacol Ther 126 2010 56 68
41. G.A. Garden, and T. Moller Microglia biology in health and disease J Neuroimmune Pharmacol 1 2006 127 137 (Pubitemid 44257488)
42. P. Gelosa, R. Ballerio, C. Banfi, E. Nobili, A. Gianella, and A. Pignieri Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, increases survival in stroke-prone rats by preventing systemic inflammation and endothelial dysfunction: Comparison with aspirin and rosuvastatin J Pharmacol Exp Ther 334 2010 199 205
43. A.K. Ghose, V.N. Viswanadhan, and J.J. Wendoloski A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases J Comb Chem 1 1999 55 68
44. D. Goren, A.T. Horowitz, S. Zalipsky, M.C. Woodle, Y. Yarden, and A. Gabizon Targeting of stealth liposomes to erbB-2 (Her/2) receptor: In vitro and in vivo studies Br J Cancer 74 1996 1749 1756 (Pubitemid 26401894)
45. D. Gosselin, and S. Rivest MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation Mol Psychiatry 13 2008 480 497 (Pubitemid 351556030)
46. M. Gynther, K. Laine, J. Ropponen, J. Leppanen, A. Mannila, and T. Nevalainen Large neutral amino acid transporter enables brain drug delivery via prodrugs J Med Chem 51 2008 932 936 (Pubitemid 351304700)
47. M. Gynther, J. Ropponen, K. Laine, J. Leppanen, P. Haapakoski, and L. Peura Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats J Med Chem 52 2009 3348 3353
48. M. Haluska, and M.L. Anthony Osmotic blood-brain barrier modification for the treatment of malignant brain tumors Clin J Oncol Nurs 8 2004 263 267
49. J. Haskins, L. Gu, E.S. Wittchen, J. Hibbard, and B.R. Stevenson ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin J Cell Biol 141 1998 199 208 (Pubitemid 28182652)
50. B.T. Hawkins, and T.P. Davis The blood-brain barrier/neurovascular unit in health and disease Pharmacol Rev 57 2005 173 185 (Pubitemid 41043883)
51. R.A. Hawkins, A. Mokashi, and I.A. Simpson An active transport system in the blood-brain barrier may reduce levodopa availability Exp Neurol 195 2005 267 271 (Pubitemid 41116831)
52. M. Hellstrom, H. Gerhardt, M. Kalen, X. Li, U. Eriksson, and H. Wolburg Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis J Cell Biol 153 2001 543 553 (Pubitemid 34280141)
53. F.J. Huang, W.K. You, P. Bonaldo, T.N. Seyfried, E.B. Pasquale, and W.B. Stallcup Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse Dev Biol 344 2 2010 1035 1046
54. J.D. Huber, R.D. Egleton, and T.P. Davis Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier Trends Neurosci 24 2001 719 725 (Pubitemid 33097539)
55. J.D. Huber, R.L. VanGilder, and K.A. Houser Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats AJP Heart Circ Physiol 291 2006 H2660 H2668
56. A. Hyong, V. Jadhav, S. Lee, W. Tong, J. Rowe, and J.H. Zhang Rosiglitazone, a PPAR gamma agonist, attenuates inflammation after surgical brain injury in rodents Brain Res 1215 2008 218 224
57. K. Ishiwata, K. Kawamura, K. Yanai, and N.H. Hendrikse In vivo evaluation of P-glycoprotein modulation of 8 PET radioligands used clinically J Nucl Med 48 2007 81 87 (Pubitemid 47555379)
58. D. Katz, J.K. Taubenberger, B. Cannella, D.E. McFarlin, C.S. Raine, and H.F. McFarland Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis Ann Neurol 34 1993 661 669 (Pubitemid 23333237)
59. C. Kenney, C. Hunter, and J. Jankovic Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders Mov Disord 22 2007 193 197 (Pubitemid 46374760)
60. A.G. Kermode, A.J. Thompson, P. Tofts, D.G. MacManus, B.E. Kendall, and D.P. Kingsley Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications Brain 113 Pt 5 1990 1477 1489 (Pubitemid 20385925)
61. M.H. Kim, H.J. Maeng, K.H. Yu, K.R. Lee, T. Tsuruo, and D.D. Kim Evidence of carrier-mediated transport in the penetration of donepezil into the rat brain J Pharm Sci 99 2010 1548 1566
62. H.K. Kimelberg Functions of mature mammalian astrocytes: A current view Neuroscientist 16 2010 79 106
63. J.A. Koziol, and A.C. Feng On the analysis and interpretation of outcome measures in stroke clinical trials: Lessons from the SAINT I study of NXY-059 for acute ischemic stroke Stroke 37 2006 2644 2647 (Pubitemid 44454693)
64. R.A. Kroll, M.A. Pagel, L.L. Muldoon, S. Roman-Goldstein, S.A. Fiamengo, and E.A. Neuwelt Improving drug delivery to intracerebral tumor and surrounding brain in a rodent model: A comparison of osmotic versus bradykinin modification of the blood-brain and/or blood-tumor barriers Neurosurgery 43 1998 879 886
65. M. Krueger, and I. Bechmann CNS pericytes: Concepts, misconceptions, and a way out Glia 58 2010 1 10
66. M.E. Kutcher, and I.M. Herman The pericyte: Cellular regulator of microvascular blood flow Microvasc Res 77 2009 235 246
67. C.H. Lai, K.H. Kuo, and J.M. Leo Critical role of actin in modulating BBB permeability Brain Res Brain Res Rev 50 2005 7 13 (Pubitemid 41607512)
68. A. Lazarowski, L. Czornyj, F. Lubienieki, E. Girardi, S. Vazquez, and C. D'Giano ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy Epilepsia 48 Suppl 5 2007 140 149 (Pubitemid 47512215)
69. C.Y. Lee, and G.E. Landreth The role of microglia in amyloid clearance from the AD brain J Neural Transm 117 8 2010 949 960
70. J.M. Lee, G. Zhai, Q. Liu, E.R. Gonzales, K. Yin, and P. Yan Vascular permeability precedes spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats Stroke 38 2007 3289 3291 (Pubitemid 350175751)
71. H.D. Lewis Jr., J.W. Davis, D.G. Archibald, W.E. Steinke, T.C. Smitherman, and J.E. Doherty III Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study N Engl J Med 309 1983 396 403 (Pubitemid 13033964)
72. B.J. Li, Q. Tang, D. Cheng, C. Qin, F.Y. Xie, and Q. Wei Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque Nat Med 11 2005 944 951 (Pubitemid 41294439)
73. H.L. Liu, M.Y. Hua, P.Y. Chen, P.C. Chu, C.H. Pan, and H.W. Yang Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment Radiology 255 2 2010 415 425
74. M. Lohle, and H. Reichmann Clinical neuroprotection in Parkinson's disease - Still waiting for the breakthrough J Neurol Sci 289 2010 104 114
75. F.M. Longo, T. Yang, J.K. Knowles, Y. Xie, L.A. Moore, and S.M. Massa Small molecule neurotrophin receptor ligands: Novel strategies for targeting Alzheimer's disease mechanisms Curr Alzheimer Res 4 2007 503 506 (Pubitemid 350248381)
76. C. Luna-Tortos, M. Fedrowitz, and W. Loscher Several major antiepileptic drugs are substrates for human P-glycoprotein Neuropharmacology 55 2008 1364 1375
77. C. Luna-Tortos, M. Fedrowitz, and W. Loscher Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy Neuropharmacology 58 2010 1019 1032
78. N. Marchi, L. Angelov, T. Masaryk, V. Fazio, T. Granata, and N. Hernandez Seizure-promoting effect of blood-brain barrier disruption Epilepsia 48 2007 732 742 (Pubitemid 46587627)
79. A.M. Marini, M. Popolo, H. Pan, N. Blondeau, and R.H. Lipsky Brain adaptation to stressful stimuli: A new perspective on potential therapeutic approaches based on BDNF and NMDA receptors CNS Neurol Disord Drug Targets 7 2008 382 390
80. A.L. Marsland, J.M. McCaffery, M.F. Muldoon, and S.B. Manuck Systemic inflammation and the metabolic syndrome among middle-aged community volunteers Metabolism 59 12 2010 1801 1808
81. I. Martin-Padura, S. Lostaglio, M. Schneemann, L. Williams, M. Romano, and P. Fruscella Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration J Cell Biol 142 1998 117 127 (Pubitemid 28341144)
82. J.H. McCarty Cell adhesion and signaling networks in brain neurovascular units Curr Opin Hematol 16 2009 209 214
83. B.W. McColl, N.J. Rothwell, and S.M. Allan Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice J Neurosci 28 2008 9451 9462
84. F. Montecucco, A. Pende, A. Quercioli, and F. Mach Inflammation in the pathophysiology of essential hypertension J Nephrol 24 1 2011 23 24
85. J.V. Murphy, R. Torkelson, I. Dowler, S. Simon, and S. Hudson Vagal nerve stimulation in refractory epilepsy: The first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center Arch Pediatr Adolesc Med 157 2003 560 564 (Pubitemid 36693547)
86. E.A. Nagelhus, T.M. Mathiisen, and O.P. Ottersen Aquaporin-4 in the central nervous system: Cellular and subcellular distribution and coexpression with KIR4.1 Neuroscience 129 2004 905 913 (Pubitemid 39556243)
87. J. Neuhaus, W. Risau, and H. Wolburg Induction of blood-brain barrier characteristics in bovine brain endothelial cells by rat astroglial cells in transfilter coculture Ann N Y Acad Sci 633 1991 578 580
88. S. Obrador, and L.M. Larramendi Four cases of cerebral hemispherectomy: Remote clinical and electroencephalographic results Rev Esp Otoneurooftalmol Neurocir 12 1953 389 393
89. W.G. Ondo, P.A. Hanna, and J. Jankovic Tetrabenazine treatment for tardive dyskinesia: Assessment by randomized videotape protocol Am J Psychiatry 156 1999 1279 1281 (Pubitemid 29374894)
90. D. Papahadjopoulos, T.M. Allen, A. Gabizon, E. Mayhew, K. Matthay, and S.K. Huang Sterically stabilized liposomes: Improvements in pharmacokinetics and antitumor therapeutic efficacy Proc Natl Acad Sci U S A 88 1991 11460 11464 (Pubitemid 21916061)
91. W.M. Pardridge Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids Neurochem Res 23 1998 635 644 (Pubitemid 28173568)
92. W.M. Pardridge Molecular Trojan horses for blood-brain barrier drug delivery Discov Med 6 2006 139 143
93. W.M. Pardridge CNS drug design based on principles of blood-brain barrier transport J Neurochem 70 1998 1781 1792 (Pubitemid 28207799)
94. W.M. Pardridge Targeting neurotherapeutic agents through the blood-brain barrier Arch Neurol 59 2002 35 40 (Pubitemid 34052553)
95. W. Penfield, and M. Baldwin Temporal lobe seizures and the technic of subtotal temporal lobectomy Ann Surg 136 1952 625 634
96. Y. Persidsky, S.H. Ramirez, J. Haorah, and G.D. Kanmogne Blood-brain barrier: Structural components and function under physiologic and pathologic conditions J Neuroimmune Pharmacol 1 2006 223 236 (Pubitemid 44244128)
97. R.W. Persky, L.C. Turtzo, and L.D. McCullough Stroke in women: Disparities and outcomes Curr Cardiol Rep 12 2010 6 13
98. S. Prakash, M. Malhotra, and V. Rengaswamy Nonviral siRNA delivery for gene silencing in neurodegenerative diseases Meth Mol Biol 623 2010 211 229
99. G.M. Puddu, E. Cravero, G. Arnone, A. Muscari, and P. Puddu Molecular aspects of atherogenesis: New insights and unsolved questions J Biomed Sci 12 2005 839 853 (Pubitemid 43081666)
100. L. Qian, P.M. Flood, and J.S. Hong Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy J Neural Transm 117 8 2010 971 979
101. N.G. Rainov, and H. Ren Clinical trials with retrovirus mediated gene therapy-What have we learned? J Neurooncol 65 2003 227 236 (Pubitemid 37526815)
102. H. Ren, T. Boulikas, K. Lundstrom, A. Soling, P.C. Warnke, and N.G. Rainov Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene-A phase I/II clinical protocol J Neurooncol 64 2003 147 154 (Pubitemid 36992469)
103. R.R. Rigor, B.T. Hawkins, and D.S. Miller Activation of PKC isoform beta(I) at the blood-brain barrier rapidly decreases P-glycoprotein activity and enhances drug delivery to the brain J Cereb Blood Flow Metab 30 2010 1373 1383
104. P.T. Ronaldson, K.M. Demarco, L. Sanchez-Covarrubias, C.M. Solinsky, and T.P. Davis Transforming growth factor-beta signaling alters substrate permeability and tight junction protein expression at the blood-brain barrier during inflammatory pain J Cereb Blood Flow Metab 29 2009 1084 1098
105. C.L. Rosen, V.A. DiNapoli, T. Nagamine, and T. Crocco Influence of age on stroke outcome following transient focal ischemia J Neurosurg 103 2005 687 694 (Pubitemid 43193876)
106. K. Sahakyan, B.E. Klein, C.E. Myers, M.Y. Tsai, and R. Klein Novel risk factors in long-term hypertension incidence in type 1 diabetes mellitus Am Heart J 159 2010 1074 1080
107. J.M. Sancho, J.M. Ribera, M.J. Romero, V. Martin-Reina, P. Giraldo, and E. Ruiz Compassionate use of intrathecal depot liposomal cytarabine as treatment of central nervous system involvement in acute leukemia: Report of 6 cases Haematologica 91 2006 ECR02
108. S.I. Savitz, and W.R. Schabitz A critique of SAINT II: Wishful thinking, dashed hopes, and the future of neuroprotection for acute stroke Stroke 39 2008 1389 1391 (Pubitemid 351440723)
109. S.W. Scheff, D.A. Price, F.A. Schmitt, and E.J. Mufson Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment Neurobiol Aging 27 2006 1372 1384 (Pubitemid 44279897)
110. T. Schondorf, G. Lubben, E. Karagiannis, E. Erdmann, T. Forst, and A. Pfutzner Increased prevalence of cardiovascular disease and risk biomarkers in patients with unknown type 2 diabetes visiting cardiology specialists: Results from the DIASPORA study Diab Vasc Dis Res 7 2010 145 150
111. J. Schramm, and H. Clusmann The surgery of epilepsy Neurosurgery 62 Suppl 2 2008 463 481
112. G. Silvestrelli, A. Lanari, L. Parnetti, D. Tomassoni, and F. Amenta Treatment of Alzheimer's disease: From pharmacology to a better understanding of disease pathophysiology Mech Ageing Dev 127 2006 148 157 (Pubitemid 43165613)
113. C. Song, and H. Wang Cytokines mediated inflammation and decreased neurogenesis in animal models of depression Prog Neuropsychopharmacol Biol Psychiatry 2010
114. J.M. Starr, A.J. Farrall, P. Armitage, B. McGurn, and J. Wardlaw Blood-brain barrier permeability in Alzheimer's disease: A case-control MRI study Psychiatry Res 171 2009 232 241
115. D.M. Tishler, K.I. Weinberg, D.R. Hinton, N. Barbaro, G.M. Annett, and C. Raffel MDR1 gene expression in brain of patients with medically intractable epilepsy Epilepsia 36 1995 1 6
116. A. Tuttolomondo, S.R. Di, R.D. Di, A. Serio, G. D'Aguanno, and P.S. La Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: Relationship with TOAST subtype, outcome and infarct site J Neuroimmunol 215 2009 84 89
117. M. Ujiie, D.L. Dickstein, D.A. Carlow, and W.A. Jefferies Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model Microcirculation 10 2003 463 470 (Pubitemid 39004272)
118. K. Ulbrich, T. Knobloch, and J. Kreuter Targeting the insulin receptor: Nanoparticles for drug delivery across the blood-brain barrier (BBB) J Drug Target 19 2 2011 125 132
119. J. Vaamonde, J.M. Flores, R. Weisser, R. Ibanez, and J.A. Obeso The duration of the motor response to apomorphine boluses is conditioned by the length of a prior infusion in Parkinson's disease Mov Disord 24 2009 762 765
120. S. Wassertheil-Smoller Stroke in women Nutr Metab Cardiovasc Dis 20 6 2010 419 425
121. H.C. Wijesuriya, J.Y. Bullock, R.L. Faull, S.B. Hladky, and M.A. Barrand ABC efflux transporters in brain vasculature of Alzheimer's subjects Brain Res 1358 2010 228 238
122. K.J. Williams, A.R. Tall, C. Bisgaier, and R. Brocia Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages J Clin Invest 79 1987 1466 1472 (Pubitemid 17099651)
123. K.A. Witt, T.J. Gillespie, J.D. Huber, R.D. Egleton, and T.P. Davis Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability Peptides 22 2001 2329 2343
124. H. Wolburg, J. Neuhaus, U. Kniesel, B. Krauss, E.M. Schmid, and M. Ocalan Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes J Cell Sci 107 Pt 5 1994 1347 1357 (Pubitemid 24177334)
125. F.Y. Yang, Y.S. Lin, K.H. Kang, and T.K. Chao Reversible blood-brain barrier disruption by repeated transcranial focused ultrasound allows enhanced extravasation J Control Release 2010
126. B. Yulug, E. Ozan, A.S. Gonul, and E. Kilic Brain-derived neurotrophic factor, stress and depression: A minireview Brain Res Bull 78 2009 267 269
127. Y. Zhang, F. Calon, C. Zhu, R.J. Boado, and W.M. Pardridge Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism Hum Gene Ther 14 2003 1 12 (Pubitemid 36126683)
128. Z. Zhong, R. Deane, Z. Ali, M. Parisi, Y. Shapovalov, and M.K. O'Banion ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration Nat Neurosci 11 2008 420 422 (Pubitemid 351441888)