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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

About 70% of stroke victims present with comorbid diseases such as diabetes and hypertension. The integration of comorbidities in pre-clinical experimental design is important in understanding the mechanisms involved in the development of stroke injury and recovery. We recently showed that administr...

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Autores principales: Jackson-Cowan, LaDonya, Eldahshan, Wael, Dumanli, Selin, Dong, Guangkuo, Jamil, Sarah, Abdul, Yasir, Althomali, Waleed, Baban, Babak, Fagan, Susan C., Ergul, Adviye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866408/
https://www.ncbi.nlm.nih.gov/pubmed/33572986
http://dx.doi.org/10.3390/ijms22031356
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author Jackson-Cowan, LaDonya
Eldahshan, Wael
Dumanli, Selin
Dong, Guangkuo
Jamil, Sarah
Abdul, Yasir
Althomali, Waleed
Baban, Babak
Fagan, Susan C.
Ergul, Adviye
author_facet Jackson-Cowan, LaDonya
Eldahshan, Wael
Dumanli, Selin
Dong, Guangkuo
Jamil, Sarah
Abdul, Yasir
Althomali, Waleed
Baban, Babak
Fagan, Susan C.
Ergul, Adviye
author_sort Jackson-Cowan, LaDonya
collection PubMed
description About 70% of stroke victims present with comorbid diseases such as diabetes and hypertension. The integration of comorbidities in pre-clinical experimental design is important in understanding the mechanisms involved in the development of stroke injury and recovery. We recently showed that administration of compound C21, an angiotensin II type 2 receptor agonist, at day 3 post-stroke improved sensorimotor outcomes by lowering neuroinflammation in diabetic male animals. In the current study, we hypothesized that a delayed administration of C21 would also lower chronic inflammation post-stroke in diabetic female animals. Young female diabetic rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Three days post-stroke, rats were administered C21 or vehicle in drinking water at a dose of 0.12 mg/kg/day for 4 weeks. The impact of C21 on microglial polarization was analyzed by flow cytometry in vivo and in vitro. Compound 21 treatment improved fine motor skills after MCAO through modulation of the microglia/macrophage inflammatory properties. In addition, C21 increased M2 polarization and reduced the M1:M2 ratio in vitro. In conclusion, delayed administration of C21 downregulates post-stroke inflammation in female diabetic animals. C21 may be a useful therapeutic option to lower neuro-inflammation and improve the post-stroke recovery in diabetes.
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spelling pubmed-78664082021-02-07 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 Jackson-Cowan, LaDonya Eldahshan, Wael Dumanli, Selin Dong, Guangkuo Jamil, Sarah Abdul, Yasir Althomali, Waleed Baban, Babak Fagan, Susan C. Ergul, Adviye Int J Mol Sci Article About 70% of stroke victims present with comorbid diseases such as diabetes and hypertension. The integration of comorbidities in pre-clinical experimental design is important in understanding the mechanisms involved in the development of stroke injury and recovery. We recently showed that administration of compound C21, an angiotensin II type 2 receptor agonist, at day 3 post-stroke improved sensorimotor outcomes by lowering neuroinflammation in diabetic male animals. In the current study, we hypothesized that a delayed administration of C21 would also lower chronic inflammation post-stroke in diabetic female animals. Young female diabetic rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Three days post-stroke, rats were administered C21 or vehicle in drinking water at a dose of 0.12 mg/kg/day for 4 weeks. The impact of C21 on microglial polarization was analyzed by flow cytometry in vivo and in vitro. Compound 21 treatment improved fine motor skills after MCAO through modulation of the microglia/macrophage inflammatory properties. In addition, C21 increased M2 polarization and reduced the M1:M2 ratio in vitro. In conclusion, delayed administration of C21 downregulates post-stroke inflammation in female diabetic animals. C21 may be a useful therapeutic option to lower neuro-inflammation and improve the post-stroke recovery in diabetes. MDPI 2021-01-29 /pmc/articles/PMC7866408/ /pubmed/33572986 http://dx.doi.org/10.3390/ijms22031356 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jackson-Cowan, LaDonya
Eldahshan, Wael
Dumanli, Selin
Dong, Guangkuo
Jamil, Sarah
Abdul, Yasir
Althomali, Waleed
Baban, Babak
Fagan, Susan C.
Ergul, Adviye
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866408/
https://www.ncbi.nlm.nih.gov/pubmed/33572986
http://dx.doi.org/10.3390/ijms22031356
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