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Updated: Jun 3, 2026
A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion
Published on: May 31, 2024
Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury
Jia Shen1, Xiao-Yin Bai, Yuan Qin
1Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Abstract:
Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP.
Insights
Interrupted reperfusion protects against brain injury by reducing NADPH oxidase activity and associated superoxide levels. This mechanism enhances neuron survival and improves cognitive function after ischemia/reperfusion events.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Ischemia/reperfusion (I/R) injury is a significant cause of neurological damage.
- Interrupted reperfusion strategies aim to mitigate I/R injury.
- The role of NADPH oxidase in I/R-induced neural injury requires further elucidation.
Purpose of the Study:
- To investigate the involvement of NADPH oxidase in the neuroprotective effects of interrupted reperfusion.
- To determine if interrupted reperfusion modulates NADPH oxidase expression, assembly, and activity.
Main Methods:
- Global I/R injury was induced in mice, with groups receiving interrupted reperfusion or apocynin treatment.
- Behavioral tests assessed motor coordination and spatial learning/memory.
- Nissl staining evaluated neuron survival.
- Biochemical assays measured superoxide levels, NADPH oxidase subunit expression (gp91(phox), p47(phox)), p47(phox) translocation, and Rac1 activation.
Main Results:
- Interrupted reperfusion significantly improved motor coordination, reduced bradykinesia, and enhanced spatial learning and memory.
- Neuron survival rates were higher in interrupted reperfusion and apocynin-treated groups compared to the I/R group.
- NADPH oxidase activity, indicated by superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation, was reduced by interrupted reperfusion.
Conclusions:
- Interrupted reperfusion confers neural protection against global I/R injury.
- This protection is partly mediated by decreased expression and assembly of NADPH oxidase.
- Reduced Rac1-GTP availability by interrupted reperfusion further inhibits assembled NADPH oxidase activation.
