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Blood-neural Barrier: Intercellular Communication at Glio-Vascular Interface

  • Kim, Jeong-Hun ;
  • Kim, Jin-Hyoung ;
  • Park, Jeong-Ae ;
  • Lee, Sae-Won ;
  • Kim, Woo-Jean ;
  • Yu, Young-Suk ;
  • Kim, Kyu-Won
  • Received : 2006.05.29
  • Published : 2006.07.31

Abstract

The blood-neural barrier (BNB), including blood-brain barrier (BBB) and blood-retinal barrier (BRB), is an endothelial barrier constructed by an extensive network of endothelial cells, astrocytes and neurons to form functional 'neurovascular units', which has an important role in maintaining a precisely regulated microenvironment for reliable neuronal activity. Although failure of the BNB may be a precipitating event or a consequence, the breakdown of BNB is closely related with the development and progression of CNS diseases. Therefore, BNB is most essential in the regulation of microenvironment of the CNS. The BNB is a selective diffusion barrier characterized by tight junctions between endothelial cells, lack of fenestrations, and specific BNB transporters. The BNB have been shown to be astrocyte dependent, for it is formed by the CNS capillary endothelial cells, surrounded by astrocytic end-foot processes. Given the anatomical associations with endothelial cells, it could be supposed that astrocytes play a role in the development, maintenance, and breakdown of the BNB. Therefore, astrocytes-endothelial cells interaction influences the BNB in both physiological and pathological conditions. If we better understand mutual interactions between astrocytes and endothelial cells, in the near future, we could provide a critical solution to the BNB problems and create new opportunities for future success of treating CNS diseases. Here, we focused astrocyte-endothelial cell interaction in the formation and function of the BNB.

Keywords

Astrocyte;Blood brain barrier;Blood neural barrier;Blood retinal barrier;Central nervous system;Endothelial cell

References

  1. Abbott, N. J. (2000) Inflammatory mediators and modulation of blood-brain barrier permeability. Cell. Mol. Neurobiol. 20, 131-147 https://doi.org/10.1023/A:1007074420772
  2. Abbott, N. J. (2002) Astrocyte-endothelial interactions and bloodbrain barrier permeability. J. Anat. 200, 629-638 https://doi.org/10.1046/j.1469-7580.2002.00064.x
  3. Abbott, N. J. (2004) Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem. Int. 45, 545-552 https://doi.org/10.1016/j.neuint.2003.11.006
  4. Anderson, J. M., Fanning, A. S., Lapierre, L. and Van Itallie, C. M. (1995) Zonula occludens (ZO)-1 and ZO-2: membrane-associated guanylate kinase homologues (MAGUKs) of the tight junction. Biochem. Soc. Trans. 23, 470-475 https://doi.org/10.1042/bst0230470
  5. Bandopadhyay, R., Orte, C., Lawrenson, J. G., Reid, A. R., De Silva, S. and Allt, G. (2001) Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J. Neurocytol. 30, 35-44 https://doi.org/10.1023/A:1011965307612
  6. Bauer, H. C. and Bauer, H. (2000) Neural induction of the bloodbrain barrier: still an enigma. Cell. Mol. Neurobiol. 20, 13-28 https://doi.org/10.1023/A:1006939825857
  7. Begley, D. J. and Brightman, M. W. (2003) Structural and functional aspects of the blood-brain barrier. Prog. Drug Res. 61, 40-78
  8. Braun, L. D., Cornford, E. M. and Oldendorf, W. H. (1980) Newborn rabbit blood-brain barrier is selectively permeable and differs substantially from the adult. J. Neurochem. 34, 147-152 https://doi.org/10.1111/j.1471-4159.1980.tb04633.x
  9. Brightman, M. W. and Reese, T. S. (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell. Biol. 40, 648-677 https://doi.org/10.1083/jcb.40.3.648
  10. Brillault, J., Berezowski, V., Cecchelli, R. and Dehouck, M. P. (2002) Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood brain barrier during ischaemia. J. Neurochem. 83, 807-817 https://doi.org/10.1046/j.1471-4159.2002.01186.x
  11. Davson, H. and Oldendorf, W. H. (1967) Transport in the central nervous system. Proc. R. Soc. Med. 60, 326-328
  12. Dehouck, M. P., Meresse, S., Delorme, P., Fruchart, J. C. and Cecchelli, R. (1990) An easier, reproducible, and massproduction method to study the blood-brain barrier in vitro. J. Neurochem. 54, 1798-1801 https://doi.org/10.1111/j.1471-4159.1990.tb01236.x
  13. Dehouck, M. P., Vigne, P., Torpier, G., Breittmayer, J. P., Cecchelli, R. and Frelin, C. (1997) Endothelin-1 as a mediatore of endothelial cell-percyte interactions in bovine brain capillaries. J. Cereb. Blood Flow Metab. 17, 464-469 https://doi.org/10.1097/00004647-199704000-00012
  14. Deli, M. A., Descamps, L., Dehouck, M. P., Cecchelli, R., Joo, F., Abraham, C. S. and Torpier, G. (1995) Exposure of tumor necrosis factor-a to luminal membrane of bovine capillary endothelial cells cocultured with astrocytes induces a delayed increase of permeability and cytoplasmic stress formation of actin. J. Neurosci. Res. 41, 717-726 https://doi.org/10.1002/jnr.490410602
  15. Dermietzel, R. and Krause, D. (1991) Molecular anatomy of the blood-brain barrier as defined by immunocytochemistry. Int. Rev. Cytol. 12, 57-109
  16. de Vries, H. E. And Dijkstra, D. D. (2004) Mononuclear phagocytes at the blood-brain barrier in multiple sclerosis; in Blood-Spinal Cord and Brain Barriers in Health and Disease, Sharma, H. S. and Westman, J. (eds.) pp. 409-417, Elsevier, San Diego, USA
  17. Dore-Duffy, P., Owen, C., Balabanov, R., Murphy, S., Beaumont, T. and Rafols, J. A. (2000) Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc. Res. 60, 55-69 https://doi.org/10.1006/mvre.2000.2244
  18. Fanning, A. S., Jameson, B. J., Jesaitis, L. A. and Anderson, J. M. (1998) The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J. Biol. Chem. 273, 29745-29753 https://doi.org/10.1074/jbc.273.45.29745
  19. Farkas, E. and Luiten, P. G. (2001) Cerebral microvascular pathology in aging and Alzheimer's disease. Prog. Neurobiol. 64, 575-611 https://doi.org/10.1016/S0301-0082(00)00068-X
  20. Fenstermacher, J., Gross, P., Sposito, N., Acuff, V., Pettersen, S. and Gruber, K. (1988) Structural and functional variations in capillary systems within the brain. Ann. N.Y. Acad. Sci. 529, 21-30 https://doi.org/10.1111/j.1749-6632.1988.tb51416.x
  21. Fischer, S., Wobben, M., Kleinstuck, J., Renz, D. and Schaper, W. (2000) Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells. Am. J. Physiol. Cell. Physiol. 279, 935-944 https://doi.org/10.1152/ajpcell.2000.279.4.C935
  22. Furuse, M., Fujita, K., Hiiragi, T., Fujimoto, K. and Tsukita, S.(1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occluding. J. Cell Biol. 141, 1539-1550 https://doi.org/10.1083/jcb.141.7.1539
  23. Gonul, E., Duz, B., Kahraman, S., Kayali, H., Kubar, A. and Timurkaynak, E. (2002) Early pericyte response to brain hypoxia in cats: an ultrastructural study. Microvasc. Res. 64, 116-119 https://doi.org/10.1006/mvre.2002.2413
  24. Gursoy-Ozdemir, Y., Qiu, J., Matsuoka, N., Bolay, H., Bermpohl, D., Jin, H., Wang, X., Rosenberg, G. A., Lo, E. H. and Moskowitz, M. A. (2004) Cortical spreading depression activates and upregulates MMP-9. J. Clin. Investig. 113, 1447-1455 https://doi.org/10.1172/JCI200421227
  25. Haskins, J., Gu, L., Wittchen, E. S. and Hibbard, J. (1998) Stevenson BR. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occluding. J. Cell Biol. 141, 199-208 https://doi.org/10.1083/jcb.141.1.199
  26. Hayashi, Y., Nomura, M., Yamagishi, S., Harada, S., Yamashita, J. and Yamamoto, H. (1997) Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia 19, 13-26 https://doi.org/10.1002/(SICI)1098-1136(199701)19:1<13::AID-GLIA2>3.0.CO;2-B
  27. Hickey, W. F. (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36, 118-124
  28. Hirase, T., Staddon, J. M., Saitou, M., Ando-Akatsuka, Y., Itoh, M., Furuse, M., Fujimoto, K., Tsukita, S. and Rubin, L. L. (1997) Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci. 110, 1603-1613
  29. Hori, S., Ohtsuki, S., Hosoya, K., Nakashima, E. and Terasaki, T. (2004) A pericyte- derived angiopoietin-1 multimeric complex induces occluding gene expression in brain capillary endothelial cells through Tie-2 activation in vitro. J. Neurochem. 89, 503-513 https://doi.org/10.1111/j.1471-4159.2004.02343.x
  30. Huber, J. D., Egleton, R. D. and Davis, T. P. (2001) Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier. Trends Neurosci. 24, 719-725 https://doi.org/10.1016/S0166-2236(00)02004-X
  31. Pardridge, W. M. (2005) The blood-brain barrier: bottle neck in brain drug development. NeuroRx 2, 3-14 https://doi.org/10.1602/neurorx.2.1.3
  32. Hurst, R. D. and Fritz, I. B. (1996) Properties of an immortalized vascular endothelial/glioma cell co-culture model of the bloodbrain barrier. J. Cell. Physiol. 167, 81-88 https://doi.org/10.1002/(SICI)1097-4652(199604)167:1<81::AID-JCP9>3.0.CO;2-8
  33. Iadecola, C. (1993) Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link? Trends Neurosci. 16, 206-214 https://doi.org/10.1016/0166-2236(93)90156-G
  34. Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M. and Tsukita, S. (1999) Direct binding of three tight junctionassociated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J. Cell Biol. 147, 1351-1363 https://doi.org/10.1083/jcb.147.6.1351
  35. Janzer, R. C. and Raff, M. C. (1997) Astrocytes induce bloodbrain barrier properties in endothelial cells. Nature 325, 253-257
  36. Kacem, K., Lacombe, P., Seylaz, J. and Bonvento, G. (1998) Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23, 1-10 https://doi.org/10.1002/(SICI)1098-1136(199805)23:1<1::AID-GLIA1>3.0.CO;2-B
  37. Kniesel, U. and Wolburg, H. (2000) Tight junctions of the bloodbrain barrier. Cell. Mol. Neurobiol. 20, 57-76 https://doi.org/10.1023/A:1006995910836
  38. Krum, J. M., Kenyon, K. L. and Rosenstein, J. M. (1997) Expression of blood-brain barrier characteristics following neuronal loss and astroglial damage after administration of anti-Thy-1 immunotoxin. Exp. Neurol. 146, 33-45 https://doi.org/10.1006/exnr.1997.6528
  39. Kuchler-Bopp, S., Delanoy, J. P., Artault, J. C., Zaepfel, M. and Dietrich, J. R. (1999) Astrocytes induce several blood-brain barrier properties in non-neural endothelial cells. Neuroreport 10, 1347-1353 https://doi.org/10.1097/00001756-199904260-00035
  40. Lee, E. J., Hung, Y. C. and Lee, M. Y. (1999) Early alterations in cerebral hemodynamics, brain metabolism and blood-brain barrier permeability in experimental intracerebral hemorrhage. J. Neurosurg. 91, 1013-1019 https://doi.org/10.3171/jns.1999.91.6.1013
  41. Lee, S. W., Kim, W. J., Choi, Y. K., Song, H. S., Son, M. J., Gelman, I. H., Kim, Y. J. and Kim, K. W. (2003) SSeCKS regulates angiogenesis and tight junction formation in bloodbrain barrier. Nat. Med. 9, 900-906 https://doi.org/10.1038/nm889
  42. Leybaert, L. (2005) Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling? J. Cereb. Blood Flow Metab. 25, 2-16 https://doi.org/10.1038/sj.jcbfm.9600001
  43. Machein, M. R., Kullmer, J., Fiebich, B. L., Plate, K. H. and Warnke, P. C. (1999) Vascular endothelial growth factor expression, vascular volume, and capillary permeability in human brain tumors. Neurosurgery 44, 732-740 https://doi.org/10.1097/00006123-199904000-00022
  44. Mark, K. S. and Davis, T. (2002) Cerebral microvascular changes in permeability and tight junctions induced by hypoxiareoxygenation. Am. J. Physiol- Heart C. 282, 1485-1494 https://doi.org/10.1152/ajpheart.00645.2001
  45. McAllister, M. S. (2001) Mechanisms of glucose transporter at the blood-brain barrier: an in vitro study. Brain Res. 409, 20-30
  46. Mi, H., Haeberle, H. and Barres, B. A. (2001) Induction of astrocyte differentiation by endothelial cells. J. Neurosci. 21, 1538-1547 https://doi.org/10.1523/JNEUROSCI.21-05-01538.2001
  47. Oldendorf, W. H., Conford, M. E. and Brown, W. J. (1977) The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann. Neurol. 1, 409-417 https://doi.org/10.1002/ana.410010502
  48. Orte, C., Lawrenson, J. G., Finn, T. M., Reid, A. R. and Alit, G. A. (1999) Comparison of blood-brain barrier and blood-nerve barrier endothelial cell markers. Anat. Embryol. (Berl) 199, 509-517 https://doi.org/10.1007/s004290050248
  49. Oztas, B., Akgul, S. and Arslan, F. B. (2004) Influence of surgical pain stress on the blood-brain barrier permeability in rats. Life Sci. 74, 1973-1979 https://doi.org/10.1016/j.lfs.2003.07.054
  50. Pardridge, W. M. (1999) Blood-brain barrier biology and methodology. J. Neurovirol. 5, 556-569 https://doi.org/10.3109/13550289909021285
  51. Peridsky, Y., Ghorpade, A., Rasmussen, J., Limoges, J., Liu, X. J., Stins, M., Fiala, M., Way, D., Kim, K. S., Witte, M. H., Weinand, M., Carhart, L., Gendelman, H. E. (1999) Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1encephalitis. Am. J. Pathol. 15, 1599-1611
  52. Petty, M. A. and Lo, E. H. (2002) Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog. Neurobiol. 68, 311-323 https://doi.org/10.1016/S0301-0082(02)00128-4
  53. Rascher, G., Fischmann, A., Kruger, S., Duffner, F., Grote, E. H. and Wolburg, H. (2002) Extracellular matrix and the bloodbrain barrier in glioblastoma multiforme: Spatial segregation of tenascin and agrin. Acta Neuropathol. 104, 85-91 https://doi.org/10.1007/s00401-002-0524-x
  54. Reese, T. S. and Karnovsky, M. J. (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol. 34, 207-217 https://doi.org/10.1083/jcb.34.1.207
  55. Reichert, M., Muller, T. and Hunziker, W. (2000) The PDZ domains of zonula occludens-1 induce an epithelial to mesenchymal transition of Madin-Darby canine kidney cells. Evidence for a role of betacatenin/Tcf/Lef signaling. J. Biol. Chem. 275, 9492-9500
  56. Risau, W. and Wolburg, H. (1990) Development of blood-brain barrier. Trends Neurosci. 13, 174-178 https://doi.org/10.1016/0166-2236(90)90043-A
  57. Schinkel, A. H. (1999) P-glycoprotein, a gatekeeper in the bloodbrain barrier. Adv. Drug Deliv. Rev. 36, 179-194 https://doi.org/10.1016/S0169-409X(98)00085-4
  58. Schlageter, K. E., Molnar, P., Lapin, G. D. and Groothuis, D. R. (1999) Microvessel organization and structure in experimental brain tumor: microvessel populations with distinctive structural and functional properties. Microvasc. Res. 58, 312-328 https://doi.org/10.1006/mvre.1999.2188
  59. Schroeter, M. L., Mertsch, K., Giese, H., Muller, S., Sporbert, A., Hickel, B. and Blasig, I. E. (1999) Astrocytes enhance radical defence in capillary endothelial cells constituting the bloodbrain barrier. FEBS Lett. 449, 241-244 https://doi.org/10.1016/S0014-5793(99)00451-2
  60. Schwaninger, M., Sallmann, S., Petersen, N., Schneider, A., Prinz, S., Libermann, T. A. and Spranger, M. (1999) Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-kB. J. Neurochem. 73, 1461-1466 https://doi.org/10.1046/j.1471-4159.1999.0731461.x
  61. Sedlakova, R., Shivers, R. R. and Del Maestro, R. F. (1999) Ultrastructure of the blood-brain barrier in the rabbit. J. Submicronsc. Cytol. Pathol. 31, 149-161
  62. Song, H. S., Son, M. J., Lee, Y. M., Kim, W. J., Lee, S. W., Kim, C. W. and Kim, K. W. (2002) Oxygen tension regulates the maturation of the blood-brain barrier. Biochem. Biophys. Res. Commun. 290, 325-331 https://doi.org/10.1006/bbrc.2001.6205
  63. Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T. N., Yancopoulos, G. D. and McDonald, D. M. (1999) Leakageresistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286, 2511-2514 https://doi.org/10.1126/science.286.5449.2511
  64. Wardlaw, J. M., Sandercock, P. A., Dennis, M. S. and Starr, J. (2003) Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia? Stroke 34, 806-812 https://doi.org/10.1161/01.STR.0000058480.77236.B3
  65. Wolburg, H. (2006) The endothelial frontier; in Blood-Brain Interfaces-from Ontogeny to Artificial Barriers, Dermietzel, R., Spray, D. and Nedergaard, M. (eds.) pp. 77-107, Wiley-VCH, Weinheim, Germany
  66. Wolburg, H. and Lippoldt, A. (2002) Tight junctions of the bloodbrain barrier. Vasc. Pharmacol. 38, 323-337 https://doi.org/10.1016/S1537-1891(02)00200-8
  67. Xu, J. and Ling, E. A. (1994) Studies of the ultrastructure and permeability of the blood-brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers. J. Anat. 84, 227-237

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  41. Intravenously administered gold nanoparticles pass through the blood–retinal barrier depending on the particle size, and induce no retinal toxicity vol.20, pp.50, 2009, https://doi.org/10.1088/0957-4484/20/50/505101
  42. Inhibition of Protein Kinase C δ Attenuates Blood-Retinal Barrier Breakdown in Diabetic Retinopathy vol.176, pp.3, 2010, https://doi.org/10.2353/ajpath.2010.090398
  43. Non-vertebrate models to study parasite invasion of the central nervous system vol.27, pp.1, 2011, https://doi.org/10.1016/j.pt.2010.08.003
  44. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System vol.2013, 2013, https://doi.org/10.1155/2013/578480
  45. Histochemistry and cell biology: the annual review 2010 vol.135, pp.2, 2011, https://doi.org/10.1007/s00418-011-0781-7
  46. In vitro and ex vivo retina angiogenesis assays vol.17, pp.3, 2014, https://doi.org/10.1007/s10456-013-9398-x
  47. Dysregulation of coagulation in cerebral malaria vol.166, pp.2, 2009, https://doi.org/10.1016/j.molbiopara.2009.03.006
  48. Effect of blood-retinal barrier development on formation of selenite nuclear cataract in rat vol.216, pp.2-3, 2013, https://doi.org/10.1016/j.toxlet.2012.11.016
  49. The perivascular niche microenvironment in brain tumor progression vol.9, pp.15, 2010, https://doi.org/10.4161/cc.9.15.12710
  50. Peripheral nerve pericytes modify the blood-nerve barrier function and tight junctional molecules through the secretion of various soluble factors vol.226, pp.1, 2011, https://doi.org/10.1002/jcp.22337
  51. Regulation of claudins in blood-tissue barriers under physiological and pathological states vol.1, pp.3, 2013, https://doi.org/10.4161/tisb.24782
  52. Endothelin-1 Reduces P-Glycoprotein Transport Activity in an In Vitro Model of Human Adult Blood–brain Barrier vol.28, pp.7, 2008, https://doi.org/10.1007/s10571-008-9277-y
  53. The brain tumor microenvironment vol.60, pp.3, 2012, https://doi.org/10.1002/glia.21264
  54. Advances in the understanding of retinal drug disposition and the role of blood–ocular barrier transporters 2013, https://doi.org/10.1517/17425255.2013.796928
  55. Retinal ganglion cell death in glaucoma: Exploring the role of neuroinflammation vol.787, 2016, https://doi.org/10.1016/j.ejphar.2016.03.064
  56. PPAR-, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches vol.2008, 2008, https://doi.org/10.1155/2008/295784
  57. In situ calcium mapping in the mouse retina via time-of-flight secondary ion mass spectrometry: modulation of retinal angiogenesis by calcium ion in development and oxygen-induced retinopathy vol.86, pp.5, 2008, https://doi.org/10.1139/O08-125
  58. Oxidized low density lipoprotein-induced senescence of retinal pigment epithelial cells is followed by outer blood–retinal barrier dysfunction vol.44, pp.5, 2012, https://doi.org/10.1016/j.biocel.2012.02.005
  59. Quantitative Proteomics Reveals β2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability vol.15, pp.5, 2016, https://doi.org/10.1074/mcp.M115.053249
  60. SPARC expression by cerebral microvascular endothelial cells in vitro and its influence on blood-brain barrier properties vol.13, pp.1, 2016, https://doi.org/10.1186/s12974-016-0657-9
  61. Permeability assessment of the focused ultrasound-induced blood–brain barrier opening using dynamic contrast-enhanced MRI vol.55, pp.18, 2010, https://doi.org/10.1088/0031-9155/55/18/012
  62. Astrocyte, the star avatar: redefined vol.33, pp.3, 2008, https://doi.org/10.1007/s12038-008-0060-5
  63. The brain tumor microenvironment vol.59, pp.8, 2011, https://doi.org/10.1002/glia.21136
  64. Pathogenesis, diagnosis and treatment of neuromyelitis optica: Changing concept of an old disease vol.1, pp.3, 2010, https://doi.org/10.1111/j.1759-1961.2010.00011.x
  65. ATP-sensitive potassium channels: A promising target for protecting neurovascular unit function in stroke vol.37, pp.2, 2010, https://doi.org/10.1111/j.1440-1681.2009.05190.x
  66. Investigation of barrier characteristics in the hyaloid-retinal vessel of zebrafish vol.89, pp.6, 2011, https://doi.org/10.1002/jnr.22607
  67. Interaction between pericytes and endothelial cells leads to formation of tight junction in hyaloid vessels vol.36, pp.5, 2013, https://doi.org/10.1007/s10059-013-0228-1
  68. Meteorin regulates angiogenesis at the gliovascular interface vol.56, pp.3, 2008, https://doi.org/10.1002/glia.20600
  69. The role of amino acid transporters in GSH synthesis in the blood–brain barrier and central nervous system vol.61, pp.3, 2012, https://doi.org/10.1016/j.neuint.2012.05.019
  70. Neural crest derivatives in ocular development: Discerning the eye of the storm vol.105, pp.2, 2015, https://doi.org/10.1002/bdrc.21095
  71. Role of Inflammation in Diabetic Retinopathy vol.19, pp.4, 2018, https://doi.org/10.3390/ijms19040942
  72. Signaling-chemokine axis network in brain as a sanctuary site for metastasis vol.234, pp.4, 2018, https://doi.org/10.1002/jcp.27305