Angiotensin receptor (AT2R) agonist C21 prevents cognitive decline after permanent stroke in aged animals-A randomized double- blind pre-clinical study

Behav Brain Res. 2019 Feb 1:359:560-569. doi: 10.1016/j.bbr.2018.10.010. Epub 2018 Oct 5.

Abstract

Post stroke cognitive impairment (PSCI) is an understudied, long-term complication of stroke, impacting nearly 30-40% of all stroke survivors. No cure is available once the cognitive deterioration manifests. To our knowledge, this is the first study to investigate the long-term effects of C21 treatment on the development of PSCI in aged animals. Treatments with C21 or vehicle were administered orally, 24 h post-stroke, and continued for 30 days. Outcome measures for sensorimotor and cognitive function were performed using a sequence of tests, all blindly conducted and assessed at baseline as well as at different time points post-stroke. Our findings demonstrate that the angiotensin receptor (AT2R) agonist C21 effectively prevents the development of PSCI in aged animals.

Keywords: AT2 receptor; Compound 21; Permanent stroke; Post-stroke cognitive impairment; RAS modulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Aging / drug effects*
  • Aging / physiology
  • Aging / psychology
  • Animals
  • Body Weight / drug effects
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / prevention & control*
  • Disease Models, Animal
  • Double-Blind Method
  • Drug Evaluation, Preclinical
  • Male
  • Motor Activity / drug effects
  • Nootropic Agents / pharmacology*
  • Random Allocation
  • Rats, Wistar
  • Receptor, Angiotensin, Type 2 / agonists*
  • Recovery of Function / drug effects
  • Stroke / complications
  • Stroke / drug therapy*
  • Stroke / physiopathology
  • Stroke / psychology
  • Sulfonamides / pharmacology*
  • Thiophenes / pharmacology*
  • Time Factors

Substances

  • N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide
  • Nootropic Agents
  • Receptor, Angiotensin, Type 2
  • Sulfonamides
  • Thiophenes