Abstract Details

Title Sirtuin 1 Mediated Modulation of Inflammasome Signaling Confers Neuroprotection in Rodent Model of Ischemic Stroke Following Endovascular Mesenchymal Stem Cell Therapy

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S33 - Cerebrovascular Disease: Basic Sciences and Cohort Studies (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Background

Stroke affects millions across the globe due to its long-term effects. Several preclinical as well as clinical studies have supported the therapeutic use of stem cells in stroke patients to enhance their quality of life. Prior studies from our lab have showed that 1*10⁵ MSCs when administered intraarterially (IA) render neuroprotection by modulating the inflammasome expression. SIRT1 is an important enzyme essential for regulating cellular metabolism, which is reduced following an ischemic episode. Therefore, targeting the SIRT1 dependent pathways paves a way for developing novel therapeutic strategies for cerebral ischemia.

Objective

The present study aims to understand the role of mesenchymal stem cells (MSCs) in regulating the brain sirtuin 1 (SIRT1) levels following stroke and the involvement of SIRT1 in regulating inflammasome signaling towards reduction of cellular apoptosis and neuroprotection.

Design/Methods Ovariectomized Sprague Dawley rats were infused intraarterially with 1*10⁵ MSCs at 6hrs post middle cerebral artery occlusion (MCAo). Following 24hrs of MCAo, animals were examined for functional and behavioral outcomes. Brains were harvested for molecular studies. Inhibition study with SIRT1 specific inhibitor was also performed.

Results Significant improvement in behavioral and motor functional outcomes and reduction in infarct size was observed following infusion of MSCs intraarterially at 6hrs post stroke. Increase in average neuronal length and density were also observed. Increased expression of SIRT1, BDNF and concomitant reduction in the expression of different inflammatory and apoptotic markers in the brain cortical regions were observed following MSCs administration.

Conclusions Our results provide primary evidence that IA MSCs therapy post-stroke regulates SIRT1 to modulate NFκB pathway towards mitigating inflammasome signaling and cellular apoptosis. The intraarterial (IA) approach for administering MSCs is highly relevant in the present clinical settings. Our study is the first to report that neuroprotective effects of IA MSCs in rodent focal ischemia is mediated by SIRT1 regulation of inflammasome signaling.

Authors/Disclosures
Deepaneeta Sarmah, M Pharm (National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A)) PRESENTER	Miss Sarmah has nothing to disclose.
	No disclosure on file
Antra Chaudhary, MS (Pharm) (National Institute of Pharmaceutical Education and Research (NIPER))	Ms. CHAUDHARY has nothing to disclose.
	No disclosure on file
	No disclosure on file
Dileep R. Yavagal, MD, FAAN (University of Miami Miller School of Medicine)	Dr. Yavagal has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vascular Dynamics. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Guidepoint. The institution of Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving as a Consultant for Medtronic. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving as a Consultant for Cerenovus/Johnson & Johnson. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving as a Consultant for Stryker. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving as a Consultant for Poseydon. Dr. Yavagal has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Athersys. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gravity Medical Technology. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Poseydon. Dr. Yavagal has stock in Poseydon. Dr. Yavagal has stock in Galaxy Therapeutics. Dr. Yavagal has stock in Stentrode. Dr. Yavagal has stock in Gravity Medical. Dr. Yavagal has stock in Gravity Medical Technology. Dr. Yavagal has stock in Athersys. Dr. Yavagal has stock in Rapid Medical . Dr. Yavagal has received intellectual property interests from a discovery or technology relating to health care. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as a Medicolegal Expert with Royal Carribean Cruise Line. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as a Medicolegal Consultant with Carnival Cruise Line.
Pallab Bhattacharya, PhD (National Institute of Pharmaceutical Education and Research (NIPER),Ahmedabad.)	Dr. Bhattacharya has nothing to disclose.