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

被引:17
作者
Jackson-Cowan, LaDonya [1 ,2 ,3 ,4 ]
Eldahshan, Wael [2 ,3 ]
Dumanli, Selin [5 ,6 ]
Dong, Guangkuo [7 ]
Jamil, Sarah [5 ,6 ]
Abdul, Yasir [5 ,6 ]
Althomali, Waleed [2 ,3 ]
Baban, Babak [8 ]
Fagan, Susan C. [2 ,3 ]
Ergul, Adviye [3 ,5 ,6 ]
机构
[1] Univ Georgia Med Partnership, Augusta Univ, Dept Med, Athens, GA 30602 USA
[2] Univ Georgia, Coll Pharm, Program Clin & Expt Therapeut, Augusta, GA 30912 USA
[3] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA 30912 USA
[4] Augusta Univ, Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA
[5] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA
[6] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA
[7] Augusta Univ, Med Coll Georgia, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA
[8] Dent Coll Georgia, Dept Oral Biol, Augusta, GA 30912 USA
关键词
ischemic stroke; diabetes; neuro-inflammation; AT2; receptor; microglial polarization; ESTROUS-CYCLE; EXPERIMENTAL STROKE; COMPOUND; 21; RISK-FACTOR; T-CELL; BRAIN; STIMULATION; MOUSE; IL-17; MICE;
D O I
10.3390/ijms22031356
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1 / 14
页数:14
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