Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke

Wael Eldahshan, Mohammed A. Sayed, Mohamed E. Awad, Heba A. Ahmed, Ellen Gillis, Waleed Althomali, Bindu Pillai, Abdulkarim Alshammari, Ladonya Jackson, Guangkuo Dong, Jennifer C. Sullivan, Marion A. Cooley, Mohammed Elsalanty, Adviye Ergul, Susan C. Fagan

Research output: Contribution to journalArticlepeer-review

Abstract

Angiotensin signaling is known to be sexually dimorphic. Although it is a well-studied target for intervention in stroke and cognitive impairment, female studies are rare. With females suffering a disproportionately greater negative impact of stroke and dementia vs. males, effective interventions are of utmost urgency. The aim of the current study was to determine the impact of activation of the angiotensin II type 2 receptor (AT2R) with the agonist compound 21 (C21) on the development of post-stroke cognitive impairment, after experimental ischemic stroke. Ovariectomized (OVX) spontaneously hypertensive rats (SHRs) were subjected to 1 h of middle cerebral artery occlusion (MCAO). At 24 h, rats with a significant neurologic deficit were randomized to receive either saline or C21 (0.03 mg/kg/day) intraperitoneally (IP) for 5 days, then orally (0.12 mg/kg/day) for a total of 6 weeks. Cognitive function, brain structure by MRI and vascular architecture by microCT angiography were measured. C21 preserved cognitive function, specifically spatial memory, and improved vascular density in the ischemic hemisphere at 6 weeks, reflecting both arteriogenesis and angiogenesis. In conclusion, C21 prevented cognitive impairment after stroke, likely through a mechanism involving vascular protection and restoration.

Original languageEnglish (US)
Article number106904
JournalVascular Pharmacology
Volume141
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Angiotensin II receptor subtype 2 (AT2R)
  • Female rodents
  • Post-stroke cognitive impairment (PSCI)
  • Spontaneously hypertensive rats (SHRs)
  • microCT angiography

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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