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Updated: Feb 21, 2026
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke
Hiroshi Yao1, Tetsuro Ago2, Takanari Kitazono3
1Laboratory of Neurochemistry, National Hospital Organization Hizen Psychiatric Center, Saga 842-0192, Japan. rinkenyao@abelia.ocn.ne.jp.
Abstract:
Several experimental studies have indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) exert detrimental effects on ischemic brain tissue; Nox-knockout mice generally exhibit resistance to damage due to experimental stroke following middle cerebral artery occlusion (MCAO). Furthermore, our previous MCAO study indicated that infarct size and blood-brain barrier breakdown are enhanced in mice with pericyte-specific overexpression of Nox4, relative to levels observed in controls. However, it remains unclear whether Nox affects the stroke outcome directly by increasing oxidative stress at the site of ischemia, or indirectly by modifying physiological variables such as blood pressure or cerebral blood flow (CBF). Because of technical problems in the measurement of physiological variables and CBF, it is often difficult to address this issue in mouse models due to their small body size; in our previous study, we examined the effects of Nox activity on focal ischemic injury in a novel congenic rat strain: stroke-prone spontaneously hypertensive rats with loss-of-function in Nox. In this review, we summarize the current literature regarding the role of Nox in focal ischemic injury and discuss critical issues that should be considered when investigating Nox-related pathophysiology in animal models of stroke.
Insights
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) worsen stroke damage. Understanding Nox
Area of Science:
- Neuroscience
- Cardiovascular Research
- Oxidative Stress Biology
Background:
- Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are implicated in ischemic brain injury.
- Nox-knockout mice show resistance to stroke damage after middle cerebral artery occlusion (MCAO).
- Pericyte-specific Nox4 overexpression exacerbates infarct size and blood-brain barrier disruption in MCAO models.
Purpose of the Study:
- To review the literature on the role of Nox in focal ischemic injury.
- To discuss the direct versus indirect effects of Nox on stroke outcomes.
- To highlight critical considerations for investigating Nox in animal stroke models.
Main Methods:
- Review of existing experimental studies on Nox and ischemic stroke.
- Analysis of findings from MCAO models in mice and rats.
- Discussion of challenges in measuring physiological variables in small animal stroke models.
Main Results:
- Experimental evidence suggests Nox activity contributes to ischemic brain damage.
- The precise mechanisms by which Nox affects stroke outcome (direct oxidative stress vs. indirect physiological changes) require further elucidation.
- Technical difficulties in physiological measurements in rodents complicate mechanistic studies.
Conclusions:
- Nox enzymes play a significant role in the pathophysiology of ischemic stroke.
- Further research is needed to differentiate direct and indirect effects of Nox on stroke.
- Careful consideration of methodological challenges is crucial for advancing the study of Nox in stroke models.
