Abstract
Abstract TMP58: Post Stroke Activation of Angiotensin II Type 2 Receptors Shows Sustained Neuroprotective Effects in Aged Rats
Stroke (1970), Vol.47(suppl_1)
02/2016
DOI: 10.1161/str.47.suppl_1.tmp58
Abstract
Abstract only
Background:
The renin angiotensin system is a promising target for stroke neuroprotection and therapy through activation of angiotensin type II receptors (AT2Rs). Compound 21 (C21), a selective non-peptide AT2R agonist, has been shown to exhibit neuroprotection and improve stroke outcomes in preclinical studies. Stimulation of AT2Rs is believed to counteract the negative effects of angiotensin type 1 receptor and provide distinctive beneficial anti-inflammatory and neurotropic effects. We hypothesized that C21 given after stroke through peripheral injections would have sustained neuroprotective effects in aged rats.
Methods:
Aged adult male SD rats (18-20 months) underwent ischemic stroke by monofilament middle cerebral artery occlusion (MCAO) and were randomly divided into two groups that received intraperitoneal (IP) injections of either 0.9% NaCl or 0.03mg/kg C21 at reperfusion (90 min), 24h, and 48h after stroke. All animals received blinded neurological exams at 4h, 24h, 72h, 7d, 14d, and 21d post-stroke. Infarct size was assessed by magnetic resonance imaging at 21 days.
Results:
Post-stroke treatment with C21 significantly improved neurological function, as evidenced by neurological testing using Rotarod and somatosensory dysfunction exams. At 7d and 14d after stroke, C21-treated rats had significantly increased Rotarod times versus saline-treated rats, and at 21d, the somatosensory function was significantly improved as measured by time to removal of paw adhesive. Infarct volume tended to be non-significantly decreased by C21 treatment at 21d post-stroke.
Conclusions:
Our findings indicate that targeting the renin-angiotensin system, specifically by stimulation of AT2Rs with C21, improves neurological function in aged rats with stroke over a sustained period of 21 days. These findings encourage further research into the renin-angiotensin system and specifically AT2Rs, and offers hope for effective alternatives for treating stroke.
Details
- Title: Subtitle
- Abstract TMP58: Post Stroke Activation of Angiotensin II Type 2 Receptors Shows Sustained Neuroprotective Effects in Aged Rats
- Creators
- Jacob D Isenberg - University of FloridaDouglas M Bennion - University of FloridaAlexander J Irwin - University of FloridaAllison T Harmel - University of FloridaEduardo Candelario-Jalil - University of FloridaColin Sumners - University of Florida
- Resource Type
- Abstract
- Publication Details
- Stroke (1970), Vol.47(suppl_1)
- DOI
- 10.1161/str.47.suppl_1.tmp58
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 02/2016
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984962622702771
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