The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
NADPH Oxidase Plays a Central Role in Blood-Brain Barrier Damage in Experimental Stroke
Abstract
Background and Purpose— Cerebral ischemia/reperfusion is associated with reactive oxygen species (ROS) generation, and NADPH oxidases are important sources of ROS. We hypothesized that NADPH oxidases mediate blood-brain barrier (BBB) disruption and contribute to tissue damage in ischemia/reperfusion. Methods— Ischemia was induced by filament occlusion of the middle cerebral artery in mice for 2 hours followed by reperfusion. BBB permeability was measured by Evans blue extravasation. Monolayer permeability was determined from transendothelial electrical resistance of cultured porcine brain capillary endothelial cells. Results— BBB permeability was increased in the ischemic hemisphere 1 hour after reperfusion. In NADPH oxidase–knockout (gp91phox −/− ) mice, middle cerebral artery occlusion–induced BBB disruption and lesion volume were largely attenuated compared with those in wild-type mice. Inhibition of NADPH oxidase by apocynin prevented BBB damage. In porcine brain capillary endothelial cells, hypoxia/reoxygenation induced translocation of the NADPH oxidase activator Rac-1 to the membrane. In vivo inhibition of Rac-1 by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin or Clostridium difficile lethal toxin B also prevented the ischemia/reperfusion–induced BBB disruption. Stimulation of porcine brain capillary endothelial cells with H 2 O 2 increased permeability, an effect attenuated by inhibition of phosphatidyl inositol 3-kinase or c -Jun N -terminal kinase but not blockade of extracellular signal–regulated kinase-1/2 or p38 mitogen-activated protein kinase. Inhibition of Rho kinase completely prevented the ROS-induced increase in permeability and the ROS-induced polymerization of the actin cytoskeleton. Conclusions— Activation of Rac and subsequently of the gp91phox containing NADPH oxidase promotes cerebral ROS formation, which then leads to Rho kinase–mediated endothelial cell contraction and disruption of the BBB. Inhibition of NAPDH oxidase is a promising approach to reduce brain injury after stroke.
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Cites
Redox Regulation of Cellular Signalling
Kamata, H., & Hirata, H. (1999) · Cellular Signalling · doi:10.1016/s0898-6568(98)00037-0 · Cited by 1,148
Vascular NAD(P)H oxidases: specific features, expression, and regulation
Lassègue, B., & Clempus, R. E. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00758.2002 · Cited by 1,032
Endres, M., Laufs, U., Huang, Z., Nakamura, T., Huang, P., Moskowitz, M. A., & Liao, J. K. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8880 · Cited by 966
Self-citationMatrix metalloproteinases in neuroinflammation
Rosenberg, G. A. (2002) · Glia · doi:10.1002/glia.10108 · Cited by 868
Wegener, J., Keese, C. R., & Giaever, I. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4919 · Cited by 769
Wang, Y. F., Tsirka, S. E., Strickland, S., Stieg, P. E., Soriano, S. G., & Lipton, S. A. (1998) · Nature Medicine · doi:10.1038/nm0298-228 · Cited by 630
Ischemic Brain Injury is Mediated by the Activation of Poly(ADP-Ribose)Polymerase
Endres, M., Wang, Z.-Q., Namura, S., Waeber, C., & Moskowitz, M. A. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199711000-00002 · Cited by 622
Self-citationAsahi, M., Asahi, K., Jung, J.-C., del Zoppo, G. J., Fini, M. E., & Lo, E. H. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200012000-00007 · Cited by 610
Görlach, A., Brandes, R. P., Nguyen, K., Amidi, M., Dehghani, F., & Busse, R. (2000) · Circulation Research · doi:10.1161/01.res.87.1.26 · Cited by 598
Self-citationAmbasta, R. K., Kumar, P., Griendling, K. K., Schmidt, H. H. H. W., Busse, R., & Brandes, R. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406486200 · Cited by 541
Self-citationWagner, A. H., Köhler, T., Rückschloss, U., Just, I., & Hecker, M. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.1.61 · Cited by 516
Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase
Walder, C. E., Green, S. P., Darbonne, W. C., Mathias, J., Rae, J., Dinauer, M. C., Curnutte, J. T., & Thomas, G. R. (1997) · Stroke · doi:10.1161/01.str.28.11.2252 · Cited by 349
Wassmann, S., Laufs, U., Bäumer, A. T., Müller, K., Konkol, C., Sauer, H., Böhm, M., & Nickenig, G. (2001) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)12257-2 · Cited by 345
Fujimura, M., Gasche, Y., Morita-Fujimura, Y., Massengale, J., Kawase, M., & Chan, P. H. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01843-0 · Cited by 340
Free radicals as triggers of brain edema formation after stroke
Heo, J. H., Han, S. W., & Lee, S. K. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.035 · Cited by 305
Vallet, P., Charnay, Y., Steger, K., Ogier-Denis, E., Kovari, E., Herrmann, F., Michel, J.-P., & Szanto, I. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.12.038 · Cited by 291
Endothelial NADPH Oxidase as the Source of Oxidants in Lungs Exposed to Ischemia or High K +
Al-Mehdi, A. B., Zhao, G., Dodia, C., Tozawa, K., Costa, K., Muzykantov, V., Ross, C., Blecha, F., Dinauer, M., & Fisher, A. B. (1998) · Circulation Research · doi:10.1161/01.res.83.7.730 · Cited by 265
gp91phox-Containing NADPH Oxidase Mediates Endothelial Dysfunction in Renovascular Hypertension
Jung, O., Schreiber, J. G., Geiger, H., Pedrazzini, T., Busse, R., & Brandes, R. P. (2004) · Circulation · doi:10.1161/01.cir.0000124223.00113.a4 · Cited by 255
Self-citationWang, Q., Tompkins, K. D., Simonyi, A., Korthuis, R. J., Sun, A. Y., & Sun, G. Y. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.060 · Cited by 235
Franke, H., Galla, H.-J., & Beuckmann, C. T. (2000) · Brain Research Protocols · doi:10.1016/s1385-299x(00)00020-9 · Cited by 227
Self-citationJunge, C. E., Sugawara, T., Mannaioni, G., Alagarsamy, S., Conn, P. J., Brat, D. J., Chan, P. H., & Traynelis, S. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235594100 · Cited by 199
Targeting Rho in Cardiovascular Disease
Laufs, U., & Liao, J. K. (2000) · Circulation Research · doi:10.1161/01.res.87.7.526 · Cited by 171
Signaling from Ras to Rac and beyond: not just a matter of GEFs
Scita, G., Tenca, P., Frittoli, E., Tocchetti, A., Innocenti, M., Giardina, G., & Di Fiore, P. P. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2393 · Cited by 170
Vecchione, C., & Brandes, R. P. (2002) · Circulation Research · doi:10.1161/01.res.0000028004.76218.b8 · Cited by 161
Self-citationFischer, S., Wiesnet, M., Renz, D., & Schaper, W. K. A. (2005) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2005.03.002 · Cited by 150
Hong, H., Zeng, J.-S., Kreulen, D. L., Kaufman, D. I., & Chen, A. F. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01270.2005 · Cited by 134
Blanc, A., Pandey, N. R., & Srivastava, A. K. (2003) · International Journal of Molecular Medicine · doi:10.3892/ijmm.11.2.229 · Cited by 128
Sohn, H., Keller, M., GLOE, T. R., Morawietz, H., Rueckschloss, U., & Pohl, U. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000026200 · Cited by 117
Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn-superoxide dismutase
Teixeira, H. D., Schumacher, R. I., & Meneghini, R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7872 · Cited by 111
Kim, G. W., Lewén, A., Copin, J. C., Watson, B. D., & Chan, P. H. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00237-8 · Cited by 96
Lagrange, P., Romero, I. A., Minn, A., & Revest, P. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00112-4 · Cited by 91
Cyclooxygenase-2 Does Not Contribute to Postischemic Production of Reactive Oxygen Species
Kunz, A. B., Anrather, J., Zhou, P., Orio, M., & Iadecola, C. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600369 · Cited by 86
Neuroprotective Effect of an Antioxidant in Ischemic Brain Injury: Involvement of Neuronal Apoptosis
Fujimura, M., Tominaga, T., & Chan, P. H. (2005) · Neurocritical Care · doi:10.1385/ncc:2:1:059 · Cited by 74
Waters, D. D., LaRosa, J. C., Barter, P. J., Fruchart, J., Gotto, A. M., Carter, R., Breazna, A., Kastelein, J. J. P., & Grundy, S. M. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.07.041 · Cited by 74
NADPH-oxidase activity is elevated in penumbral and non-ischemic cerebral arteries following stroke
Miller, A. A., Dusting, G. J., Roulston, C. L., & Sobey, C. G. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.082 · Cited by 67
Kato, N., Yanaka, K., Hyodo, K., Homma, K., Nagase, S., & Nose, T. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02918-4 · Cited by 66
Matsuzaki, I., Chatterjee, S., Debolt, K. M., Manevich, Y., Zhang, Q., & Fisher, A. B. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00025.2004 · Cited by 57
Liu, S., Liu, M., Peterson, S. L., et al. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10534 · Cited by 52
What blocks health visitors from taking on a leadership role?
Hyett, E. (2003) · Journal of Nursing Management · doi:10.1046/j.1365-2834.2003.00406.x · Cited by 43
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Forrester, S. J., Kikuchi, D. S., Hernandes, M. S., Xu, Q., & Griendling, K. K. (2018) · Circulation Research · doi:10.1161/circresaha.117.311401 · Cited by 2,081
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Candelario-Jalil, E., Dijkhuizen, R. M., & Magnus, T. (2022) · Stroke · doi:10.1161/strokeaha.122.036946 · Cited by 953
Paracrine Mechanisms of Mesenchymal Stem Cell-Based Therapy: Current Status and Perspectives
Liang, X., Ding, Y., Zhang, Y., Tse, H.-F., & Lian, Q. (2014) · Cell Transplantation · doi:10.3727/096368913x667709 · Cited by 909
Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899
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Yang, C., Hawkins, K. E., Doré, S., & Candelario-Jalil, E. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00136.2018 · Cited by 871
Metadata
- Authors
- Kahles, T., Luedike, P., Endres, M., Galla, H.-J., Steinmetz, H., Busse, R., Neumann-Haefelin, T., & Brandes, R. P.
- Venue
- Stroke
- Published
- 2007-11
- Volume
- 38
- Issue
- 11
- Pages
- 3000-3006
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2121875633
- Cited by
- 386
- References
- 39
- FWCI
- 13.85
- Type
- journal article
- Language
- en
- Open access
- closed
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