NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke
Abstract
:1. Introduction
2. Experimental Models of Stroke
2.1. Distal Middle Cerebral Artery Occlusion
2.2. Proximal MCAO
2.3. Intraluminal Suture Occlusion
2.4. Photothrombotic MCAO in Spontaneously Hypertensive Rats
2.5. Ischemic Penumbra
2.6. Nox in Experimental Models of Stroke
2.7. Nox2
2.8. Nox1
2.9. Nox4
2.10. Pericyte Nox4 in Focal Brain Ischemia
2.11. Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) with Loss-of-Function in Nox
2.12. Nox and Branching Morphogenesis
2.13. Effects of Nox on Blood Pressure
3. Perspectives—Nox Knockout in Rats
4. Concluding Comments
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Models | Anatomic Sites of MCAO | Duration | Characteristics | Disadvantage |
---|---|---|---|---|
Distal MCAO | MCAO distal to rhinal fissure | P | Distal MCAO was studied for the first time in SHRSP, revealing increased stroke sensitivity by hypertension. | The infarct size and penumbra are too small to evaluate the effects of pharmacotherapeutic agents in normotensive rats. |
Proximal MCAO | MCAO proximal to lenticulostriate arteries | P (T) | The subtemporal approach method have emerged as a standard method of proximal MCAO. | The procedure is surgically demanding and may induce local traumatic effects. |
Intraluminal suture occlusion | MCA origin and the proximal segment of ACA | T (P) | The procedure is easy to perform, minimally invasive, and does not require craniectomy. | This model has a wide ischemic zone, and the mortality rate is high in the case of PO. |
Photothrombotic MCAO | Photochemical MCAO distal to rhinal fissure | P T | Photothrombotic MCAO in SHR yields a highly reproducible infarct volume, and does not requireopening of the dura. | Same as mentioned for distal MCAO. |
Author Ref. | Year | Mice (WT: C57 Bl/6J) | T/P | BP | CBF | Nox Isoform | Outcome | Protection by KO | |
---|---|---|---|---|---|---|---|---|---|
Age | Sex | ||||||||
Walder [36] | 1997 | 8–10 wk | m | T | NA | NA | Nox2 | Infarct volume was reduced by 46% in KO mice compared with WT mice. | Yes |
Kahles [43] | 2007 | 7–9 wk | m | T | NA | NA | Nox2 | BBB disruption and lesion volume were largely attenuated in KO mice. | Yes |
Chen [37] | 2009 | NA | m | T | NA | NS | Nox2 | Mean infarct volume was 106.2 mm3 in WT mice, and 52.0 mm3 in KO mice. | Yes |
Jackman [39] | 2009 | 5–9 wk WT 8–12 wk KO | m m | T | NA | NS | Nox2 | Protection by apocynin was found in WT mice but not in KO mice. | Yes |
Brait [41] | 2010 | 6–8 wk | m+f | T/P | NA | NS | Nox2 | The larger infarction in male mice was dependent on both reperfusion and NOX2. | Yes (female) |
De Silva [42] | 2011 | NA | m | T | NA | NS | Nox2 | Smaller infarct volume was observed in KO mice than in WT mice. | Yes |
Chen [38] | 2011 | 12–16 wk | m | T | NA | NA | Nox2 | Brain infarction was 35–44% less in KO mice compared with WT mice. | Yes |
Kim [40] | 2012 | 8–12 wk | m | P | NA | NS | Nox2 | No protection by KO was found in the absence of reperfusion. | NA |
MaCann [44] | 2014 | 2–3 mo | NA | T | NA | NS | Nox2 | KO showed transient nature of protection and increased revascularization. | Yes |
Jackman [45] | 2009 | 11–17 wk | m | T | NA | NS | Nox1 | Cortical but not total infarct was increased in KO mice. | No |
Kahles [46] | 2010 | NA | m + f | T/P | NA | NA | Nox1 | Infarct volume was reduced by 44% after 1 h but not 2 h and pMCAO in KO mice. | Yes |
Kleinschnitz [48] | 2010 | 6–8 wk | m | T | NA | NA | Nox1 | Deletion of NOX4 but not NOX1 or NOX2 prevented focal ischemic injury. | No |
6–8 wk | m | T | NA | NA | Nox2 | No | |||
6–8 wk | m + f | T/P | NA | NA | Nox4 | Yes | |||
18–20 wk | m | T | NA | NA | Nox4 | Yes |
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Yao, H.; Ago, T.; Kitazono, T.; Nabika, T. NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke. Int. J. Mol. Sci. 2017, 18, 2123. https://doi.org/10.3390/ijms18102123
Yao H, Ago T, Kitazono T, Nabika T. NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke. International Journal of Molecular Sciences. 2017; 18(10):2123. https://doi.org/10.3390/ijms18102123
Chicago/Turabian StyleYao, Hiroshi, Tetsuro Ago, Takanari Kitazono, and Toru Nabika. 2017. "NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke" International Journal of Molecular Sciences 18, no. 10: 2123. https://doi.org/10.3390/ijms18102123