NADPH oxidase Nox1 contributes to ischemic injury in experimental stroke in mice
Open accessAbstract
Reactive oxygen species (ROS) are mediators of brain injury in ischemia/reperfusion. An involvement of the NADPH oxidase Nox2 has been demonstrated. In contrast, only little is known about the contribution of the Nox1 homologue in this context. Thus, we studied the role of Nox1 in early cerebral reperfusion injury in the middle cerebral artery filament occlusion model using Nox1 knockout mice. Genetic deletion of a functional Nox1 lead to a 55% attenuation in lesion size at 24h after induction of 1h ischemia (p<0.05). This result was paralleled by a significant improvement of neurological outcome, preservation of blood-brain barrier integrity and reduced cerebral edema in Nox1(y/)(-) compared to WT mice. Interestingly, no difference in infarct size between WT and Nox1(y/)(-) was observed with an occlusion time of 2h and longer. Apoptosis rate as measured by TUNEL staining was similar between the groups. Moreover, infusion of the antioxidant TEMPOL as well as of the unspecific NO-synthase inhibitor l-NAME elicited similar changes with respect to ischemic tissue damage between WT and Nox1-deficient mice. In conclusion, Nox1 is involved in the pathophysiology of cerebral ischemia. Our data however indicate that ROS-mediated direct cellular injury is unlikely to explain the protective effect achieved by genetic deletion of the enzyme.
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Studies have shown links between high NOX1 levels and hypertension, diabetes, ischemia/reperfusion injury, and coronary artery disease.
“Increased NOX1 activity is associated with vascular disease, and studies have shown links between high NOX1 levels and hypertension (1015), diabetes (163, 380, 1003), ischemia/reperfusion injury (479), and coronary artery disease (393).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [479]
Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Pathobiology of ischaemic stroke: an integrated view
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01401-0 · Cited by 3,943 · see citing works
Bederson, J. B., Pitts, L. H., Tsuji, M., Nishimura, M. C., Davis, R. L., & Bartkowski, H. (1986) · Stroke · doi:10.1161/01.str.17.3.472 · Cited by 2,681 · see citing works
Bright and dark sides of nitric oxide in ischemic brain injury
Iadecola, C. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10074-6 · Cited by 1,044 · see citing works
Interleukin 1 of the central nervous system is produced by ameboid microglia.
Giulian, D., Baker, T. J., Shih, L. C., & Lachman, L. B. (1986) · The Journal of experimental medicine · doi:10.1084/jem.164.2.594 · Cited by 859 · see citing works
The physiology and pathophysiology of nitric oxide in the brain
Guix, F. X., Uribesalgo, I., Coma, M., & Muñoz, F. J. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.001 · Cited by 708 · see citing works
Abramov, A. Y., Scorziello, A., & Duchen, M. R. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4468-06.2007 · Cited by 686 · see citing works
Ischemic Brain Injury is Mediated by the Activation of Poly(ADP-Ribose)Polymerase
Endres, M., Wang, Z., Namura, S., Waeber, C., & Moskowitz, M. A. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199711000-00002 · Cited by 622 · see citing works
NOX Enzymes in the Central Nervous System: From Signaling to Disease
Sorce, S., & Krause, K. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2578 · Cited by 472 · see citing works
Nox1 Is Involved in Angiotensin II–Mediated Hypertension: A Study in Nox1-Deficient Mice
Matsuno, K., Yamada, H., Iwata, K., Jin, D., Katsuyama, M., Matsuki, M., Takai, S., Yamanishi, K., Miyazaki, M., Matsubara, H., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.573709 · Cited by 470 · see citing works
NADPH Oxidase Plays a Central Role in Blood-Brain Barrier Damage in Experimental Stroke
Kahles, T., Luedike, P., Endres, M., Galla, H., Steinmetz, H., Busse, R., Neumann‐Haefelin, T., & Brandes, R. P. (2007) · Stroke · doi:10.1161/strokeaha.107.489765 · Cited by 386 · see citing works
Self-citationAronowski, J. A., Strong, R., & Grotta, J. C. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199710000-00006 · Cited by 385 · see citing works
NADPH Oxidases of the Brain: Distribution, Regulation, and Function
Infanger, D. W., Sharma, R. V., & Davisson, R. L. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.1583 · Cited by 362 · see citing works
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 · see citing works
Decreased blood pressure in NOX1‐deficient mice
Gavazzi, G., Banfi, B., Deffert, C., Fiette, L., Schappi, M., Herrmann, F., & Krause, K.-H. (2006) · FEBS Letters · doi:10.1016/j.febslet.2005.12.049 · Cited by 321 · see citing works
Free radicals as triggers of brain edema formation after stroke
Heo, J. H., Han, S., & Lee, S. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.035 · Cited by 306 · see citing works
Inhibition of NADPH Oxidase is Neuroprotective after Ischemia—Reperfusion
Chen, H., Song, Y. S., & Chan, P. H. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.47 · Cited by 286 · see citing works
Uyama, O., Okamura, N., Yanase, M., Narita, M., Kawabata, K., & Sugita, M. (1988) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1988.59 · Cited by 275 · see citing works
Wang, Q., Tompkins, K. D., Simonyi, Á., Korthuis, R. J., Sun, A. Y., & Sun, G. Y. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.060 · Cited by 235 · see citing works
Lee, M. Y., Martín, A. S., Mehta, P. K., Dikalova, A., Garrido, A. M., Datla, S. R., Lyons, E., Krause, K., Bánfi, B., Lambeth, J. D., et al. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.181925 · Cited by 234 · see citing works
Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase
Chéret, C., Gervais, A., Lelli, A., Colin, C., Amar, L., Ravassard, P., Mallet, J., Cumano, A., Krause, K.-H., & Mallat, M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3568-08.2008 · Cited by 225 · see citing works
Reactive Oxygen Species Derived from NOX1/NADPH Oxidase Enhance Inflammatory Pain
Ibi, M., Matsuno, K., Shiba, D., Katsuyama, M., Iwata, K., Kakehi, T., Nakagawa, T., Sango, K., Shirai, Y., Yokoyama, T., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1857-08.2008 · Cited by 156 · see citing works
Fischer, 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 148 · see citing works
NOX1 Deficiency Protects From Aortic Dissection in Response to Angiotensin II
Gavazzi, G., Deffert, C., Trocme, C., Schäppi, M., Herrmann, F. R., & Krause, K.-H. (2007) · Hypertension · doi:10.1161/hypertensionaha.107.089706 · Cited by 135 · see citing works
Willmot, M. R., Gibson, C. L., Gray, L. J., Murphy, S. P., & Bath, P. M. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.028 · Cited by 129 · see citing works
Komatsu, D., Kato, M., Nakayama, J., Miyagawa, S., & Kamata, T. (2008) · Oncogene · doi:10.1038/onc.2008.102 · Cited by 106 · see citing works
A tissue-culture approach to demyelinative disorders.
Mb, B. (1963) · PubMed · Cited by 90 · see citing works
Differential vascular functions of Nox family NADPH oxidases
Brandes, R. P., & Schröder, K. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32830c91e3 · Cited by 85 · see citing works
Self-citationNADPH oxidases 1 and 4 mediate cellular senescence induced by resveratrol in human endothelial cells
Schilder, Y. D. C., Heiß, E. H., Schachner, D., Ziegler, J., Reznicek, G., Sorescu, D., & Dirsch, V. M. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.03.013 · Cited by 85 · see citing works
NOX1/NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth
Ibi, M., Katsuyama, M., Fan, C., Iwata, K., Nishinaka, T., Yokoyama, T., & Yabe‐Nishimura, C. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.01.009 · Cited by 77 · see citing works
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 · see citing works
Jackman, K. A., Miller, A. A., Drummond, G. R., & Sobey, C. G. (2009) · Brain Research · doi:10.1016/j.brainres.2009.06.056 · Cited by 72 · see citing works
Role of NADPH oxidase in the apoptotic death of cultured cerebellar granule neurons
Coyoy-Salgado, A., Valencia, A., Guemez‐Gamboa, A., & Morán, J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.06.027 · Cited by 54 · see citing works
�brah�m, C. S., Niwa, M., Falus, A., et al. (2003) · Inflammation Research · doi:10.1007/s000110300045 · Cited by 41 · see citing works
Dai, X., Cao, X., & Kreulen, D. L. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00052.2005 · Cited by 38 · see citing works
Wakefield, I. D., March, J. E., Kemp, P. A., Valentin, J., Bennett, T., & Gardiner, S. M. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705351 · Cited by 37 · see citing works
Basset, O., Deffert, C., Foti, M., Bedard, K., Jaquet, V., Ogier‐Denis, É., & Krause, K. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2584 · Cited by 37 · see citing works
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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 · see citing works
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 · see citing works
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Ma, M. W., Wang, J., Zhang, Q., Wang, R., Dhandapani, K. M., Vadlamudi, R. K., & Brann, D. W. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0150-7 · Cited by 432 · see citing works
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Self-citationNox1, 2, 4, 5: Counting out oxidative stress
Wingler, K., Hermans, J., Schiffers, P., Moens, A., Paul, M., & Schmidt, H. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01249.x · Cited by 113 · see citing works
Sobey, C. G., Judkins, C. P., Rivera, J., Lewis, C. V., Diep, H., Lee, H. W., Kemp-Harper, B. K., Broughton, B. R. S., Selemidis, S., Gaspari, T. A., et al. (2015) · Free Radical Research · doi:10.3109/10715762.2014.992893 · Cited by 33 · see citing works
- Authors
- Kahles, T., Kohnen, A., Heumueller, S., Rappert, A., Bechmann, I., Liebner, S., Wittko, I. M., Neumann-Haefelin, T., Steinmetz, H., Schroeder, K., & Brandes, R. P.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Kahles, Timo
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 40
- Issue
- 1
- Pages
- 185-192
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2034340179
- Cited by
- 91
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 6 · 2013: 9 · 2012: 16
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- cerebral ischemia, ischemic stroke, ischemia-reperfusion injury, reactive oxygen species, middle cerebral artery occlusion, infarct size, blood-brain barrier integrity, cerebral edema, tempol, L-NAME, apoptosis, neuroprotection
- MeSH terms
- NADPH Oxidase 1, Animals, Cells, Cultured, Brain Ischemia, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, NADH, NADPH Oxidoreductases, Nerve Degeneration, Mice, Knockout, Infarction, Middle Cerebral Artery, Brain Infarction, Stroke, Mice
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