Delayed Administration of Angiotensin Receptor (AT2R) Agonist C21 Improves Survival and Preserves Sensorimotor Outcomes in Female Diabetic Rats Post-Stroke through Modulation of Microglial Activation
Abstract
:1. Introduction
2. Results
2.1. Delayed Administration of C21 Improves Survival and Sensorimotor Outcomes after Stroke
2.2. Delayed Administration of C21 Decreases Proinflammatory Microglia/Macrophages after Stroke
2.3. C21 Treatment Induces an M2 Phenotype and Lowers the M1:M2 Ratio In Vitro in the Microglial Cell Line
2.4. Stroke Did Not Significantly Alter IL-17 Levels from Microglia
2.5. At a Dose of 0.03 mg/Kg/Day Delayed Administration of C21 Does Not Significantly Alter Cognition in Female Rats
3. Discussion
4. Materials and Methods
4.1. Animal Model
4.2. Middle Cerebral Artery Occlusion (MCAO) Surgery
4.3. Treatment and Behavioral Assessments
Dose and Timing Justification
4.4. Blinding and Randomization
4.5. Cycle Synchronization
4.6. Assessment of Sensorimotor Function
4.7. Assessment of Cognitive Function
4.8. Euthanasia, Specimen Collection and Molecular Techniques
4.9. Flow Cytometry
4.10. Myelin Debris Removal and Microglial Isolation
4.11. Cellular Staining
4.12. Imaging and Analysis
4.13. Immunohistochemistry (IHC)
4.14. Cell Culture
4.15. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AT2R | Angiotensin II type 2 receptor |
BDNF | Brain-derived neurotrophic factor |
TH17 | T helper 17 |
MCAO | Middle cerebral artery occlusion |
ART | Adhesive removal test |
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Cell Types | CD11b | CD45 | TMEM119 | CD86 | TNFα | CD206 | IL-17 | CD4 |
---|---|---|---|---|---|---|---|---|
M1(CD86+/TNFα+) | + | +low | N/A | + | N/A | N/A | ||
M2(CD206+/IL10+) | + | +low | N/A | - | N/A | + | ||
Residential Microglia (TMEM119+) | + | + | + | N/A | N/A | N/A | ||
Infiltrating Macrophages | + | + | - | N/A | N/A | N/A | ||
M1 macrophages | + | + | - | + | + | N/A | ||
Inactivated microglia | + | +low | N/A | - | N/A | - | ||
IL17+ Microglia | + | +low | N/A | N/A | N/A | N/A | + | N/A |
Th17 | N/A | N/A | N/A | N/A | N/A | N/A | + | + |
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Jackson-Cowan, L.; Eldahshan, W.; Dumanli, S.; Dong, G.; Jamil, S.; Abdul, Y.; Althomali, W.; Baban, B.; Fagan, S.C.; Ergul, A. Delayed Administration of Angiotensin Receptor (AT2R) Agonist C21 Improves Survival and Preserves Sensorimotor Outcomes in Female Diabetic Rats Post-Stroke through Modulation of Microglial Activation. Int. J. Mol. Sci. 2021, 22, 1356. https://doi.org/10.3390/ijms22031356
Jackson-Cowan L, Eldahshan W, Dumanli S, Dong G, Jamil S, Abdul Y, Althomali W, Baban B, Fagan SC, Ergul A. Delayed Administration of Angiotensin Receptor (AT2R) Agonist C21 Improves Survival and Preserves Sensorimotor Outcomes in Female Diabetic Rats Post-Stroke through Modulation of Microglial Activation. International Journal of Molecular Sciences. 2021; 22(3):1356. https://doi.org/10.3390/ijms22031356
Chicago/Turabian StyleJackson-Cowan, LaDonya, Wael Eldahshan, Selin Dumanli, Guangkuo Dong, Sarah Jamil, Yasir Abdul, Waleed Althomali, Babak Baban, Susan C. Fagan, and Adviye Ergul. 2021. "Delayed Administration of Angiotensin Receptor (AT2R) Agonist C21 Improves Survival and Preserves Sensorimotor Outcomes in Female Diabetic Rats Post-Stroke through Modulation of Microglial Activation" International Journal of Molecular Sciences 22, no. 3: 1356. https://doi.org/10.3390/ijms22031356