HIF-1 at the blood-brain barrier: A mediator of permeability?

High Altitude Medicine and Biology

Volumn 13, Issue 3, 2012, Pages 153-161

  Ogunshola, Omolara O ^a   Al Ahmad, Abraham ^b  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b University of Wisconsin Madison   (United States)

Author keywords

hypoxia inducible factor; microvascular permeability; neurological disease; vascular endothelial growth factor; vcentral nervous system

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1; OXYGEN;

BLOOD BRAIN BARRIER; BRAIN HYPOXIA; BRAIN ISCHEMIA; CAPILLARY PERMEABILITY; CONFERENCE PAPER; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN FUNCTION; REOXYGENATION; SIGNAL TRANSDUCTION; TIGHT JUNCTION;

ANOXIA; BLOOD-BRAIN BARRIER; HOMEOSTASIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; ISCHEMIA; PERMEABILITY; PROCOLLAGEN-PROLINE DIOXYGENASE; SIGNAL TRANSDUCTION; TIGHT JUNCTIONS;

EID: 84866664154     PISSN: 15270297     EISSN: 15578682     Source Type: Journal    
DOI: 10.1089/ham.2012.1052     Document Type: Conference Paper

References (100)

1. Abbruscato TJ, Davis TP. (1999). Combination of hypoxia/aglycemia compromises in vitro blood-brain barrier integrity. J Pharmacol Exp Ther 289:668-675. (Pubitemid 29191217)
2. Al Ahmad A, Gassmann M, Ogunshola OO. (2009). Maintaining blood-brain barrier integrity: Pericytes perform better than astrocytes during prolonged oxygen deprivation. J Cell Physiol 218:612-622.
3. Al Ahmad A, Taboada CB, Gassmann M, Ogunshola OO. (2011). Astrocytes and pericytes differentially modulate blood-brain barrier characteristics during development and hypoxic insult. J Cereb Blood Flow Metab 31:693-705.
4. Althaus J, Bernaudin M, Petit E, Toutain J, Touzani O, Rami A. (2006). Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats. Neurochem Int 48:687-695.
5. Antonetti DA, Barber AJ, Hollinger LA, Wolpert EB, Gardner TW. (1999). Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechaism for vascular permeability in diabetic retinopathy and tumors. J Biol Chem 274:23463-23467.
6. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW. (1998). Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: Vascular endothelial growth factor decreases occlusin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 47:1953-1959. (Pubitemid 28549205)
7. Ballabh P, Braun A, Nedergaard M. (2004). The blood-brain barrier: An overview: Structure, regulation, and clinical implications. Neurobiol Dis 16:1-13. (Pubitemid 38569790)
8. Baranova O, Miranda LF, Pichiule P, Dragatsis I, Johnson RS, Chavez JC. (2007). Neuron-specific inactivation of the hypoxia inducible factor 1 alpha icreases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci 27:6320-6332. (Pubitemid 46890035)
9. Bauer AT, Burgers HF, Rabie T, Marti HH. (2010). Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. J Cereb Blood Flow Metab 30:837-848.
10. Bauer H, Zweimueller-Mayer J, Steinbacher P, Lametschwandtner A, Bauer HC. (2010). The dual role of zonula occludens (ZO) proteins. J Biomed Biotechnol 2010:402593.
11. Bazzoni G. (2011). Pathobiology of junctional adhesion molecules. Antioxid Redox Signal 15:1221-1234.
12. Bergeron M, Gidday JM, Yu AY, Semenza GL, Ferriero DM, Sharp FR. (2000). Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Ann Neurol 48:285-296.
13. Brightman MW, Reese TS. (1969). Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40:648-677.
14. Brown RC, Davis TP. (2005). Hypoxia/aglycemia alters expression of occludin and actin in brain endothelial cells. Biochem Biophys Res Commun 327:1114-1123. (Pubitemid 40142636)
15. Chen C, Hu Q, Yan J, Yang X, Shi X, Lei J, Chen L, Huang H, Han J, Zhang JH, Zhou C. (2009). Early inhibition of HIF-1alpha with small interfering RNA reduced ischemicreperfused brain injury in rats. Neurobiol Dis 33:509-517.
16. Chen W, Jadhav V, Tang J, Zhang JH. (2008). HIF-1alpha inhibition ameliorates neonatal brain injury in a rat pup hypoxicischemic model. Neurobiol Dis 31:433-441.
17. Chung NP, Mruk D, Mo MY, Lee WM, Cheng CY. (2001). A 22-amino acid synthetic peptide corresponding to the second extracellular loop of rat occlusin perturbs the blood-testis barrier and disrupts spermatogenesis reversibly in vivo. Biol Reprod 65:1340-1351. (Pubitemid 33031490)
18. Cuevas P, Gutierrez-Diaz JA, Reimers D, Dujovny M, Diaz FG, Ausman JI. (1984). Pericyte endothelial gap junctions in human cerebral capillaries. Anat Embryol (Berl) 170:155-159. (Pubitemid 14047409)
19. Dauchy S, Dutheil F, Weaver RJ, Chassoux F, Daumas-Duport C, Couraud PO, Scherrmann JM, De Waziers I, Decleves X. (2008). ABC transporters, cytochromes P450 and their main transcription factors: Expression at the human blood-brain barrier. J Neurochem 107:1518-1528.
20. Decleves X, Jacob A, Yousif S, Shawahna R, Potin S, Scherrmann JM. (2011). Interplay of drug metabolizing CYP450 enzymes and ABC transporters in the blood-brain barrier. Curr Drug Metab 12:732-741.
21. Digicaylioglu M, Lipton SA. (2001). Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NFkappaB signalling cascades. Nature 412:641-647. (Pubitemid 32772276)
22. Dore-Duffy P. (2003). Isolation and characterization of cerebral microvascular pericytes. Methods Mol Med 89:375-382.
23. Dutheil F, Jacob A, Dauchy S, Beaune P, Scherrmann JM, Decleves X, Loriot MA. (2010). ABC transporters and cytochromes P450 in the human central nervous system: Influence on brain pharmacokinetics and contribution to neurodegenerative disorders. Expert Opin Drug Metab Toxicol 6:1 1174.
24. Ehrlich, P. Das sauerstufbudurfnis des organismus, Hirschwald: Berlin 1885.
25. Engelhard, B, Coisne C. (2011). Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surroung the CNS castle. Fluids Barriers CNS 8:4.
26. Ferriero DM. (2005). Protecting neurons. Epilepsia 46:45-51. (Pubitemid 44914761)
27. Fischer S, Wobben M, Kleinstuck J, Renz D, Schaper W. (2000). Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells. Am J Physiol Cell Physiol 279:C935-944.
28. Förster C. (2008). Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol 130:55-70.
29. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. (1998). Claudin-1 and - 2: Novel integral membrane protein localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539-1550. (Pubitemid 28309169)
30. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. (1993). Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777-1788. (Pubitemid 24012933)
31. Ghersi-Egea JF, Monkkonen KS, Schmitt C, Honnorat J, Fevre-Montange M, Strazielle N. (2009). Blood-brain intercaces and cerebral drug bioavailability. Rev Neurol (Paris) 165: 1029-1038.
32. Goda N, Dozier SJ, Johnson RS. (2003). HIF-1 in cell cycle regulation, apoptosis,and tumor progression. Antioxid Redox Signal 5:467-473. (Pubitemid 37087407)
33. Grimm C, Hermann DM, Bogdanova A, Hotop S, Kilic U, Wenzel A, Kilic E, Gassmann M. (2005). Neuroprotection by hypoxic preconditioning: HIF-1 and erythropoietin protect from retinal degeneration. Semin Cell Dev Biol 16:531-538. (Pubitemid 41247876)
34. Guillemin GJ, Brew BJ. (2004). Microglia, macrophages, perivascular macrophages, and pericytes. A review of function and identification. J Leukoc Biol 75:388-397. (Pubitemid 38316367)
35. Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, Yu KT, Jaye M, Ivashchenko Y. (2001). Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ 8:367-376. (Pubitemid 32409607)
36. Haarmann A, Deiss A, Prochaska J, Foerch C, Weksler B, Romero I, Couraud P.O, Stoll G, Rieckmann P, Buttmann M. (2010). Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown. PLoS One 5:e13568.
37. Halterman MW, Federoff HJ. (1999). HIF1alpha and p53 promote hypoxia-induced delayed neuronal death in models of CNS ischemia. Exp Neurol 159:65-72. (Pubitemid 29444903)
38. Harten SK, Ashcroft M, Maxwell PH. (2010). Prolyl hydroxylase domain inhibitors: A route to HIF activation and neuroprotection. Antioxid Redox Signal 12:459-480.
39. Hartz AM, Bauer B. (2011). ABC transporters in the CNS. An inventory. Curr Pharm Biotechnol 12:656-673.
40. Hawkins BT, Davis TP. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57: 173-185. (Pubitemid 41043883)
41. Helton R, Cui J, Scheel JR, Ellison JA, Ames C, Gibson C, Blouw B, Ouyang L, Dragatsis I, Zeitlin S, Johnson RS, Lipton SA, Barlow C. (2005). Brain-specific knock-out of hypoxia-inducible factor1alpha reduces rather than increases hypoxic-ischemic damage. J Neurosci 25:4099-4107. (Pubitemid 40563385)
42. Higashida T, Kreipke CW, Rafols JA, Peng C, Schafer S, Schafer P, Ding JY, Dornbos D., 3rd; Li X, Guthikonda M, Rossi NF, Ding Y. (2011). The role of hypoxia-inducible factor-1alpha, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury. J Neurosurg 114:92-101.
43. Hirase T, Staddon JM, Saitou M, Ando-Akatsuka Y, Itoh M, Furuse M, Fujimoto K, Tsukita S, Rubin LL. (1997). Occludin as a possible detminant of tight junction permeability in endothelial cells. J Cell Sci 110:1603-1613. (Pubitemid 27338748)
44. Hofer T, Wenger H, Gassmann M. (2002). Oxygen sensing, HIF-1alpha stabilization and potential therapeutic strategies. Pflugers Arch 443:503-507. (Pubitemid 34185054)
45. Hopfl G, Ogunshola O, Gassmann M. (2004). HIFs and tumors: Causes and consequences. Am J Physiol Regul Integr Comp Physiol 286:R608-623.
46. Huber JD, Witt KA, Hom S, Egleton RD, Mark KS, Davis TP. (2001). Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol 280:H1241-1248.
47. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG., Jr. (2001). HIF alpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science 292:464-468. (Pubitemid 32335941)
48. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ. (2001). Targeting of HIFalpha to the von Hippel-Lindau ubiquitylation complex by) 2-regulated prolyl hydroxylation. Science 292:468-472. (Pubitemid 32335942)
49. Kago T, Takagi N, Date I, Takenaga Y, Takagi K, Takeo S. (2006). Cerebral ischemia enhances tyrosine phosphorylation of occludin in brain capillaries. Biochem Biophys Res Commun 339:1197-1203. (Pubitemid 41790589)
50. Kandel ER, Schwartz JH, Jessell TM. (2000). Principles of Neural Science, McGraw-Hill, Health Professions Division: New York.
51. Kaur C, Ling EA. (2008). Blood-brain barrier in hypoxic-ischemic conditions. Curr Neurovasc Res 5:71-81.
52. Koto T, Takubo K, Ishida S, Shinoda H, Inoue M, Tsubota K, Okada Y, Ikeda E. (2007). Hypoxia disrupts the barrier function of neural blood vessels through changes in the expression of claudin-5 in endothelial cells. Am J Pathol 170:1389-1397. (Pubitemid 47339345)
53. Krause G, Winkler L, Mueller SL, Haseloff RF, Piontek J, Blasig IE. (2008). Structure and function of claudins. Biochim Biophys Acta 1778:631-645.
54. Liebner S, Fischmann A, Rascher G, Duffner F, Grote EH, Kalbacher H, Wolburg H. (2000). Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol 100:323-331. (Pubitemid 30456160)
55. Liu F, Verin AD, Wang P, Day R, Wersto RP, Chrest FJ, English DK, Garcia JG. (2001). Differential regulation of sphingosine-1-phosphate- and VEGF-induced endothelial celll chemotaxis. Involvement of G(ialpha10)-linked Rho kinase activity. Am J Respir Cell Mol Biol 24:711-719. (Pubitemid 32550593)
56. Liu J, Narasimhan P, Yu F, Chan PH. (2005). Neuroprotection by hypoxic preconditioning involved oxidative stree-mediated expression of hypoxia-inducible factor and erythropoietin. Stroke 36:1264-01269.
57. Mark KS, Davis TP. (2002). Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol 282:H1485-1494. (Pubitemid 34654903)
58. Martinez-Sanchez G, Giuliani A.(2007). Cellular redox status regulates hypoxia inducible factor-1 activity. Role in tumour development. J Exp Clin Cancer Res 26:39-50. (Pubitemid 46656031)
59. Maxwell PH, Ratcliffe PJ. (2002). Oxygen sensors and angiogenesis. Semin Cell Dev Biol 13:29-37. (Pubitemid 35418312)
60. McCaffrey G, Willis CL, Staatz WD, Nametz N, Quigley CA, Hom S, Lochhead JJ, Davis TP. (2009). Occludin oligomeric assemblies at tight junctions of the blood-brain barrier are altered by hypoxia and reoxygenation stress. J Neurochem 110:58-71.
61. Miyata T, Takizawa S, van Ypersele de Strihou C. (2011). Hypoxia 1. Intracellular sensors for oxygen and oxidative stress: Novel therapeutic targets. Am J Physiol Cell Physiol 300: C226-231.
62. Morita K, Sasaki H, Furuse M, Tsukita S. (1999). Endothelial claudin: Claudin-5/TMVCf constitutes tight junction strands in endothelial cells. J Cell Biol 147:185-194. (Pubitemid 30211806)
63. Neuwelt E, Abbott NJ, Abrey L, Banks WA, Blakley B, Davis T, Engelhardt B, Grammas P, Nedergaard M, Nutt J, Pardridge W, Rosenberg GA, Smith Q, Drewes LR. (2008). Strategies to advance translational research into brain barriers. Lancet Neurol 7:84-96. (Pubitemid 350258701)
64. Nico B, Mangieri D, Crivellato E, Longo V, De Giorgis M, Capobianco C, Corsi P, Benagiano V, Roncali L, Ribatti D. (2007). HIF activation and VEGF overexpression are coupled with ZO-1 up-phosphorylation in the brain of dystrophic mdx mouse. Brain Pathol 17:399-406. (Pubitemid 47537597)
65. Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S. (2003). Size-selective loosening of the bloodbrain barrier in claudin-5-deficient mice. J Cell Biol 161: 653-660. (Pubitemid 36578587)
66. Nusrat A, Brown GT, Tom J, Drake A, Bui TT, Quan C, Mrsny RJ. (2005). Multiple protein interactions involving proposed extracellular loop domains of the tight junction protein occludin. Mol Biol Cell 16:1725-1734. (Pubitemid 40471943)
67. Ogunshola OO. (2011). In vitro modeling of the blood-brain barrier: Simplicity versis complexity. Curr Pharm Des 17: 2755-2761.
68. Ohtsuki S, Sato S, Yamaguchi H, Kamoi M, Asashima T, Terasaki T. (2007). Exogenous exprssion of claudin-5 induces barrier properties in cultured rat brain capillary endothelial cells. J Cell Physiol 210:81-86. (Pubitemid 44904703)
69. Orlova VV, Chavakis T. (2007). Regulation of vascular endothelial permeability by junctional adhesion molecules (JAM). Thromb Haemost 98:327-332. (Pubitemid 47250235)
70. Park JH, Okayama N, Gute D, Krsmanovic A, Battarbee H, Alexander JS. (1999). Hypoxia/aglycemia increases endothelial permeability: Role of second messengers and cytoskeleton. Am J Physiol 277:C1066-1074. (Pubitemid 30045963)
71. Pedram A, Razandi M, Levin ER. (2002). Deciphering vascular endothelial cell growth factor/vascular permeability factor signaling to vascular permeability. Ihibition by atrial natriuretic peptide. J Biol Chem 277:44385-44398. (Pubitemid 36157874)
72. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. (2006). Blood-brain barrier: Structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1:223-236. (Pubitemid 44244128)
73. Rajadhyaksha M, Boyden T, Liras J, El-Kattan A, Brodfuehrer J. (2011). Current advances in delivery ot biotherapeutics across the blood-brain barrier. Curr Drug Discov Technol 8:87-101.
74. Ratcliffe PJ, O'Rourke JF, Maxwell PH, Pugh CW. (1998). Oxygen sensing, hypoxia-inducible factor-1 and the regulation of mammalian gene expression. J Exp Biol 201:1153-1162. (Pubitemid 28278320)
75. Reese TS, Karnovsky MJ. (1967). Find structural localization of blood-brain barrier to exogenous peroxidase. J Cell Biol 34: 207-217.
76. Rosenberg GA. (2012). Neurological diseases in relation to the blood-brain barrier. J Cereb Blood Flow Metab 32: 1139-1151.
77. Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S. (2000). Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131-4242.
78. Schmid-Brunclik N, Burgi-Taboada C, Antoniou X, Gassmann M, Ogunshola OO. (2008). Astrocyte responses to injury: VEGF simultaneously modulates cell death and proliferation. Am J Physiol Regul Integr Comp Physiol 295:R864-873.
79. Schmidt-Kastner R, Aguirre-Chen C, Kietzmann T, Saul I, Busto R, Ginsberg MD. (2004). Nuclear localization of the hypoxiaregulated pro-apoptotic protein BNIP3 after global brain ischemia in the rat hippocampus. Brain Res 1001:133-142. (Pubitemid 38221536)
80. Semenza G. (2002). Signal transductions to hypoxia-inducible factor 1. Biochem Pharmacol 64:993-998.
81. Semenza GL. (2001). HIF-1, O(2), and the 3 PHDs: How animal cells signal hypoxia to the nucleus. Cell 107:1-3. (Pubitemid 32972030)
82. Senjo M, Ishibashi T, Terashima T, Inoue Y. (1986). Correlation between astrogliogenesis and blood-brain barrier formation: Immunocytochemical demonstration by using astroglia-specific enzyme glutatione S-transferase. Neurosci Lett 66:39-42. (Pubitemid 16110920)
83. Stenzel-Poore MP, Stevens SL, Xiong Z, Lessov NS, Harrington CA, Mori M, Meller R, Rosenzweig HL, Tobar E, Shaw TE, Chu X, Simon RP. (2003). Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: Similarity to neuroprotective strategies in hibernation and hypoxia-tolerance states. Lancet, 362:1028-1037. (Pubitemid 37186880)
84. Stewart PA. (1997). Glial-vascular relations. In: Primer on Cerebrovascular Diseases, Academic Press: London.
85. Thomas WE. (1999). Brain macrophages: On the role of pericytes and perivascular cells. Brain Res Brain Res Rev 31:42-57. (Pubitemid 30009612)
86. Van Hoecke M, Prigent-Tessier AS, Garnier PE, Bertrand NM, Filomenko R, Bettaieb A, Marie C, Beley AG. (2007). Evidence of HIF-1 functional binding activity to caspase-3 promoter after photothrombotic cerebral ischemia. Mol Cell Neurosci 34:40-77.
87. Vangeison G, Carr D, Federoff HJ, Rempe DA. (2008). The good, the bad, and the cell type-specific roles of hypoxia inducible factor-1 alpha in neurons and astrocytes. J Neurosci 28:1988-1993. (Pubitemid 351302661)
88. Vorbrodt AW, Dobrogowska DH. (2003). Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: Electron microscopist's view. Brain Res Brain Res Rev 42:221-242. (Pubitemid 36645239)
89. Wang GL, Semenza GL.(1993). Characterization of hypoxiainducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem 268:21513-21518. (Pubitemid 23320639)
90. Wang Z, Meng CJ, Shen XM, Shu Z, Ma C, Zhu GQ, Liu HX, He WC, Sun XB, Huo L, Zhang J, Chen G. (2012). Potential contribution of hypoxia-inducible factor-1alpha, aquaporin-4, and matrix metalloproteinase-9 to blood-brain barrier disruption and brain edema after experimental subarachnoid hemorrhage. J Mol Neurosci. 48:273-28.
91. Witt KA, Mark KS, Hom S, Davis TP. (2003). Effects of hypoxiareoxygenation on rat blood-brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol 285:H2820-2831. (Pubitemid 37443103)
92. Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote EH, Risau W, Engelhardt B. (2003). Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol 105:586-592. (Pubitemid 36798859)
93. Wolburg-Buchholz K, Mack AF, Steiner E, Pfeiffer F, Engelhardt B, Wolburg H. (2009). Loss of astrocyte polarity marks bloodbrain barrier impeirment during experimental autoimmune encephalomyelitis. Acta Neuropathol 118:219-233.
94. Yan J, Zhang Z, Shi H. (2012). HIF-1 is involved in high glucoseinduced paracellular permeability of brain endothelial cells. Cell Mol Life Sci 69:115-128.
95. Yan J, Zhou B, Taheri S, Shi H. (2011). Differential effects of HIF-1 inhibition by YC-1 on the overall outcome and blood-brain barrier damage in a rat model of ischemic stroke. PLoS One 6:e27798.
96. Yan L, Colandrea VJ, Hale JJ. (2010). Prolyl hydroxylase domaincontaining protein inhibitors as stabilizers of hypoxia-inducible factor: Small molecule-based therapeutics for anemia. Expert Opin Ther Pat 20:1219-1245.
97. Yeh WL, Lu DY, Lin CJ, Liou HC, Fu WM. (2007). Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC-1 through the antagonism of HIF-1alpha accumulation and VEGF expression. Mol Pharmacol 72: 440-449.
98. Yeung D, Manias JL, Stewart DJ, Nag S. (2008). Decreased junctional adhesion molecular-A expression during bloodbrain barrier breakdown. Acta Neuropathol 115:635-642.
99. Zlokovic BV. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178-1201.
100. Zlokovic BV. (2011). Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci 12:723-738.