Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema:
Hui Hu1, Hong Lu1, Zhanping He1
1Department of Radiology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University (Haikou Municipal People's Hospital), Haikou 570208, Hainan Province, China.
Abstract:
To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25-6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P < 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.
Insights
Messenger RNA interference targeting aquaporin-4 (AQP4) effectively reduces intracellular edema in rats with ischemic cerebral edema. Diffusion-weighted MRI accurately detects this edema, showing a strong correlation with AQP4 expression levels.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Molecular Biology
Background:
- Ischemic cerebral edema involves complex molecular changes, including aquaporin-4 (AQP4) expression.
- Diffusion-weighted magnetic resonance imaging (dMRI) is a key tool for diagnosing cerebral edema.
Purpose of the Study:
- To investigate the impact of messenger RNA (mRNA) interference on AQP4 expression in rats with ischemic cerebral edema.
- To evaluate the diagnostic significance of dMRI in detecting intracellular edema.
Main Methods:
- Rats with induced ischemic cerebral edema received either shRNA-AQP4 or siRNA-AQP4 via injection.
- Diffusion-weighted MRI was performed at various time points post-occlusion.
- AQP4 expression levels and intracellular edema were assessed.
Main Results:
- Increased AQP4 expression and aggravated intracellular edema were observed in control rats.
- siRNA-AQP4 treatment significantly reduced AQP4 expression and intracellular edema.
- A negative correlation (r = -0.806, P < 0.01) was found between AQP4 expression and apparent diffusion coefficient.
- dMRI accurately detected intracellular edema.
Conclusions:
- Upregulated AQP4 expression is a primary mechanism driving intracellular edema in ischemic stroke.
- AQP4 gene interference offers a potential therapeutic strategy for cerebral edema.
- dMRI is a reliable method for assessing intracellular edema severity.
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