Diabetic Stroke Promotes a Sexually Dimorphic Expansion of T Cells

Jackson, Ladonya; Li, Weiguo; Abdul, Yasir; Dong, Guangkuo; Baban, Babak; Ergul, Adviye

doi:10.1007/s12017-019-08554-6

Cited by 12 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously showed that diabetes and stroke increased the percentage of IL-17-producing T cells (Th17) within the T cell population in the brains of diabetic rats with and without stroke [ 6 ]. Therefore, we set out to determine the impact of stroke and C21 treatment of diabetic rats on the levels of IL-17 producing cells such as IL-17-producing microglia and Th17 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our lab and others have reported that HFD/STZ-induced diabetes results in cognitive impairment in female rats [ 5 , 6 , 14 , 15 , 16 , 17 ]. We also reported that delayed administration of C21 in male rats preserves cognition post-stroke [ 5 , 9 ].…”

Section: Resultsmentioning

confidence: 99%

“…A similar effect was observed when IL-17 was knocked out [ 35 ]. Lastly, we previously demonstrated that diabetes deferentially upregulates Th17 cells in diabetic females but not males [ 6 ]. These data suggest that IL-17 inhibition is critical in the acute period post-stroke and may be deferentially regulated in a males and females.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, when microglia and macrophages were depleted by short hairpin RNA (shRNA)-mediated silencing of the critical colony stimulating factor 1 receptor (CSF1R), the inflammation, demyelination, functional recovery and the cognition of the animals were improved [ 4 ]. Interestingly, we have also recently demonstrated a dichotomy of post-stroke inflammatory responses in male and female animals [ 6 ]. Diabetes differentially promotes the expansion of cerebral Th17 cells in females and induces a sexually dimorphic effect on the expansion of many T-cell profiles [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, we have also recently demonstrated a dichotomy of post-stroke inflammatory responses in male and female animals [ 6 ]. Diabetes differentially promotes the expansion of cerebral Th17 cells in females and induces a sexually dimorphic effect on the expansion of many T-cell profiles [ 6 ]. The impact of diabetes on microglia phenotype in females before and after stroke remains to be determined, and this established the first goal of the current study.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Eldahshan

Dumanli

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%