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Updated: Jun 21, 2026
A Modified Transcranial Middle Cerebral Artery Occlusion Model to Study Stroke Outcomes in Aged Mice
Published on: May 5, 2023
NOX2 inhibition with apocynin worsens stroke outcome in aged rats
Kimberly A Kelly1, Xinlan Li, Zhenjun Tan
1Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, PO Box 9530, Morgantown, WV 26506, USA.
Abstract:
This study utilized middle cerebral artery occlusion (MCAO) with tissue plasminogen activator (tPA) to assess inhibition of the NOX2 isoform of NADPH oxidase on brain injury and functional recovery in aged rats. Effects of NOX2 on the degree of brain injury and functional recovery following MCAO and tPA reperfusion was assessed in young adult and aged rats. Rats received apocynin (NOX2 inhibitor; 5 mg/kg) or saline 30 min prior to MCAO. At 24 h following MCAO, blood-brain barrier permeability (BBB), stroke infarct volume, edema formation, and oxidative damage were measured. Apocynin treatment in aged rats increased mortality rate and failed to improve functional outcome, total infarct volume, edema formation, and BBB permeability. Aged rats displayed increased BBB permeability to sucrose in the contralateral hemisphere following MCAO and diminished antioxidant capacity in the brain as compared to young adult rats. We conclude that inhibition of NOX2 in the aged rat exacerbates stroke injury and diminishes functional outcome. These results suggest age is an important factor in stroke damage and more rigorous examination of apocynin as a therapeutic agent for treatment of stroke must be done.
Insights
In aged rats, inhibiting NOX2 (NADPH oxidase) worsened stroke injury and functional recovery after MCAO and tPA treatment. Age significantly impacts stroke outcomes, necessitating further apocynin research.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Pharmacology
Background:
- Stroke remains a leading cause of disability and death.
- NADPH oxidase (NOX) enzymes, particularly NOX2, are implicated in oxidative stress and brain injury.
- Age-related changes may influence stroke pathophysiology and treatment response.
Purpose of the Study:
- To investigate the role of NOX2 inhibition in aged rats following ischemic stroke.
- To assess the impact of apocynin, a NOX2 inhibitor, on brain injury and functional recovery after middle cerebral artery occlusion (MCAO) and tissue plasminogen activator (tPA) reperfusion.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in young adult and aged rats.
- Administration of apocynin (NOX2 inhibitor) or saline prior to MCAO.
- Assessment of blood-brain barrier permeability (BBB), infarct volume, edema, oxidative damage, and functional outcomes at 24 hours post-MCAO.
Main Results:
- Apocynin treatment in aged rats increased mortality and did not improve functional outcome, infarct volume, edema, or BBB permeability.
- Aged rats exhibited increased BBB permeability and diminished antioxidant capacity compared to young rats post-MCAO.
- NOX2 inhibition exacerbated stroke injury and worsened functional outcomes in aged rats.
Conclusions:
- Inhibition of NOX2 in aged rats exacerbates stroke injury and diminishes functional recovery.
- Age is a critical factor influencing stroke damage and response to NOX2 inhibition.
- Further investigation into apocynin as a therapeutic agent for stroke is warranted, considering age-specific effects.
