Angiotensin II type 2 receptor stimulation with compound 21 improves neurological function after stroke in female rats

A pilot study

Wael Eldahshan, Tauheed Ishrat, Bindu Pillai, Mohammed A. Sayed, Abdulrahman Alwhaibi, Abdelrahman Y. Fouda, Adviye Ergul, Susan C. Fagan

Research output: Contribution to journalArticle

Abstract

The angiotensin II type 2 receptor (AT2R) agonist, compound 21 (C21), has been shown to be neurovascularly protective after ischemic stroke in male rats. In the current study, we aim to study the impact of C21 treatment on female rats. Young female Wistar rats were subjected to different durations of middle cerebral artery occlusion (MCAO) (3 h, 2 h, and 1 h) using a silicone-coated monofilament, treated at reperfusion with 0.03 mg/kg ip of C21 and followed up for different times (1, 3, and 14 days) after stroke. Behavioral tests were performed (Bederson, paw grasp, beam walk, and rotarod), and animals were euthanized for infarct size analysis and Western blot analysis. In vitro, primary male and female brain microvascular endothelial cells (ECs) were grown in culture, and the expression of the AT2R was compared between males and females. At 1 day, C21 treatment resulted in an improvement in Bederson scores. However, at 3 days and 14 days, the impact of C21 on stroke outcomes was less robust. In vitro, the expression of the AT2R was significantly higher in female ECs compared with male ECs. In conclusion, C21 improves Bederson scores after stroke in female rats when administered early at reperfusion. The ability of C21 to exert its neuroprotective effects might be affected by fluctuating levels of female hormones. NEW & NOTEWORTHY The present study shows the neuroprotective impact of C21 on ischemic stroke in female rats and how the protective effects of C21 can be influenced by the hormonal status of female rodents.

Original languageEnglish (US)
Pages (from-to)H1192-H1201
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume316
Issue number5
DOIs
StatePublished - May 1 2019

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Angiotensin Type 2 Receptor
Stroke
Endothelial Cells
Reperfusion
Aptitude
Middle Cerebral Artery Infarction
Hand Strength
Neuroprotective Agents
Silicones
Wistar Rats
Rodentia
Western Blotting
Hormones

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Angiotensin II type 2 receptor stimulation with compound 21 improves neurological function after stroke in female rats : A pilot study. / Eldahshan, Wael; Ishrat, Tauheed; Pillai, Bindu; Sayed, Mohammed A.; Alwhaibi, Abdulrahman; Fouda, Abdelrahman Y.; Ergul, Adviye; Fagan, Susan C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 316, No. 5, 01.05.2019, p. H1192-H1201.

Research output: Contribution to journalArticle

Eldahshan, Wael ; Ishrat, Tauheed ; Pillai, Bindu ; Sayed, Mohammed A. ; Alwhaibi, Abdulrahman ; Fouda, Abdelrahman Y. ; Ergul, Adviye ; Fagan, Susan C. / Angiotensin II type 2 receptor stimulation with compound 21 improves neurological function after stroke in female rats : A pilot study. In: American Journal of Physiology - Heart and Circulatory Physiology. 2019 ; Vol. 316, No. 5. pp. H1192-H1201.
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