Dynamic change of MMP-9 in diabetic stroke visualized by optical imaging and treated with CD28 superagonist
Yu Cai1, Shou Leng, Yuanyuan Ma
1Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China. jsh0836@hotmail.com.
Abstract:
Type 2 diabetes mellitus is associated with an increased risk for stroke and unfavorable outcomes following stroke. Matrix metalloproteinase-9 (MMP-9) is a potential contributor to the poor prognosis of diabetic ischemic stroke. Investigations on diabetic stroke are limited by the lack of non-invasive imaging techniques. In this study, we report a fast and ultra-sensitive MMP-activatable optical imaging probe (MMP-P12) to achieve non-invasive and real-time visualization of the dynamic expression of MMP-9 in diabetic stroke. Moreover, by using this probe, we aim to detect the therapeutic efficacy of CD28 SA in diabetic stroke. Serial near-infrared fluorescence (NIRF) imaging was performed on wild-type and STZ-induced diabetic mice after MMP-P12 probe injection on days 1, 3, and 7 post ischemic stroke. The dynamic change in MMP-9 expression after CD28 SA treatment was also imaged on days 1, 3, and 7 post stroke and confirmed by immunohistochemistry staining and western blotting. NIRF imaging showed that diabetic stroke mice presented a trend of higher levels of MMP-9. CD28 SA treatment significantly downregulated the expression of MMP-9 on day 7 post stroke. Glucose also had a downward trend in CD28 SA treated diabetic stroke mice. In conclusion, our data suggest that MMP-P12 probe successfully detect the dynamic change of MMP-9 in diabetic stroke by utilizing optical imaging. CD28 SA treatment decreased the expression of MMP-9 and could be a promising therapeutic strategy for the treatment of diabetic stroke.
Insights
A novel optical imaging probe (MMP-P12) visualizes matrix metalloproteinase-9 (MMP-9) in diabetic stroke. CD28 SA treatment reduced MMP-9 expression, offering a potential therapeutic strategy for diabetic stroke patients.
Area of Science:
- Biomedical imaging
- Neuroscience
- Endocrinology
Background:
- Type 2 diabetes mellitus increases stroke risk and worsens outcomes.
- Matrix metalloproteinase-9 (MMP-9) is implicated in poor prognosis for diabetic ischemic stroke.
- Non-invasive imaging techniques for diabetic stroke research are lacking.
Purpose of the Study:
- To develop a fast, ultra-sensitive MMP-activatable optical imaging probe (MMP-P12).
- To enable non-invasive, real-time visualization of dynamic MMP-9 expression in diabetic stroke.
- To assess the therapeutic efficacy of CD28 SA in diabetic stroke using the developed probe.
Main Methods:
- Serial near-infrared fluorescence (NIRF) imaging in wild-type and STZ-induced diabetic mice.
- Injection of MMP-P12 probe post-ischemic stroke (days 1, 3, 7).
- Confirmation of MMP-9 expression changes via immunohistochemistry and western blotting.
Main Results:
- Diabetic stroke mice showed a trend of elevated MMP-9 levels.
- CD28 SA treatment significantly downregulated MMP-9 expression by day 7 post-stroke.
- CD28 SA treatment also showed a downward trend in glucose levels.
Conclusions:
- The MMP-P12 probe effectively visualizes dynamic MMP-9 changes in diabetic stroke via optical imaging.
- CD28 SA treatment reduces MMP-9 expression, indicating its potential as a therapeutic strategy for diabetic stroke.
