Angiotensin II Type 2 Receptor Agonism Alleviates Progressive Post-stroke Cognitive Impairment in Aged Spontaneously...

Area of Science:

• Neuroscience
• Cardiovascular Research
• Aging Research

Background:

• Hypertension and aging are primary risk factors for stroke and vascular contributions to cognitive impairment and dementia (VCID).
• Existing animal models often do not fully replicate the complex interactions between these conditions.
• Spontaneously hypertensive rats (SHRs) are utilized to model age-related hypertension and its effects.

Purpose of the Study:

• To investigate cognitive impairment development in aged spontaneously hypertensive rats before and after ischemic stroke.
• To evaluate the therapeutic potential of an angiotensin II type 2 receptor (AT2R) agonist, Compound 21 (C21), in improving outcomes post-stroke.
• To assess the utility of SHRs as a translational model for studying stroke-associated VCID in aging populations.

Main Methods:

• Sixty 18-month-old SHRs underwent cognitive assessments and MRI scans over 18 months, including pre-stroke baseline and post-stroke evaluations.
• Ischemic stroke was induced, and rats were randomized to receive either C21 or plain water for 8 weeks.
• Sensorimotor function, behavioral deficits, brain swelling, atrophy, and lesion resolution were assessed.

Main Results:

• SHRs exhibited progressive cognitive decline and MRI abnormalities prior to stroke.
• Stroke led to acute brain swelling, chronic atrophy, and persistent sensorimotor deficits.
• C21 treatment significantly enhanced sensorimotor recovery and promoted resolution of ischemic lesions.

Conclusions:

• Spontaneously hypertensive rats serve as a relevant model for studying aging and stroke-associated VCID.
• Modulating AT2R signaling with C21 shows promise as a therapeutic strategy to improve sensorimotor and cognitive outcomes in aged animals post-stroke.
• This research highlights the importance of translational disease modeling for developing effective interventions.