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Abstract Details

Intra-arterial mesenchymal stem cell therapy modulates inflammasome to confer neuroprotection in animal model of ischemic stroke
Cerebrovascular Disease and Interventional Neurology
P2 - Poster Session 2 (5:30 PM-6:30 PM)
3-026

We aim to test if intra-arterial (IA) MSCs can inhibit the expression of inflammasome by attenuating ASIC1a expression to render neuroprotection.
Stroke is devastating and one of the leading causes of long-term disability worldwide. Ischemia, followed by acidosis worsens the pathology by activating the acid sensing ion channel 1a (ASIC1a). This activated ASIC1a increases the expression of NLRP1 inflammasome in a pH dependant manner that further activates the inflammatory cascade. ASIC1a once activated triggers the influx of Ca2+ions and its overload contributes to neuronal injury and death in ischemic stroke. Cell based therapy with mesenchymal stem cells (MSCs) is promising for clinical translationand reported to improve neurological outcome in rodent model. In the present study we explored the role of intra-arterial (IA) MSCs to inhibit the expression of inflammasome by attenuating ASIC1a expression to confer neuroprotection.
Sprague Dawley rodents were infused with IA MSCs at 6 hours post middle cerebral artery occlusion (MCAo) followed by 24 hours of reperfusion on the basis of expression of SDF-1. Rats were evaluated for neurodeficit and motor functions. Brains were harvested for infarct size estimation, biochemical analysis, and western blot experiments.

IA MSCs at a dose of 1x105 cells at 6 hours following ischemia confers neuroprotection as evident by the reduction in infarct volume, improvement in neurodeficit scores and motor function. An increase in GSH levels and reduction in elevated nitrite and MDA levels were observed in the IA MSCs treated animals. IA MSCs infusion also attenuated the expression of ASIC1a, NLRP1, NLRP3, ASC1, IL1β and caspase-1 in the cortical brain regions following ischemia.
 IA MSCs confers neuroprotection by attenuating acidosis by modulating NLRP1 mediated ASIC1a expression. 
Authors/Disclosures
Pallab Bhattacharya, PhD (National Institute of Pharmaceutical 好色先生 and Research (NIPER),Ahmedabad.)
PRESENTER 		Dr. Bhattacharya has nothing to disclose.
Deepaneeta Sarmah, M Pharm (National Institute of Pharmaceutical 好色先生 and Research-Ahmedabad (NIPER-A)) Miss Sarmah has nothing to disclose.
Harpreet Kaur, MD (East Portland Neurology) No disclosure on file
No disclosure on file
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.