The Involvement of Mitochondrial Dysfunction in Exacerbation of Ischemic Stroke Pathology in Chronic Kidney Disease (2213)

Objective: Present study aim to decipher the molecular mechanism by which Chronic Kidney Disease (CKD) may exacerbate ischemic stroke pathology. Background: Stroke is an incident that leads to disturbance in cerebral function leading to disability and death worldwide. Both acute and chronic kidney disease (CKD) are correlated with an enhanced risk of cerebrovascular events and stroke. The underlying mechanistic approach between stroke and impaired renal function has been explored limitedly, hence, has attracted researchers to explore in depth for developing therapeutic interventions. Design/Methods: CKD was induced in Sprague Dawley Rats by 0.5% adenine diet for 28 days followed by a middle cerebral artery occlusion (MCAo) for ischemic stroke. Rats were evaluated for neurodeficits, motor functions and were sacrificed at 24 hours post MCAo. Brains were harvested for infarct size estimations, biochemical analysis, mitochondrial respiration and protein expression studies. LCMS/MS was performed to assess homocysteine levels in brain. Results: Neurodeficit was enhanced while motor function was impaired to a greater extent in stroke+ CKD animals as compared to sham, stroke and CKD animals. Levels of MDA and nitrite were increased, and glutathione decreased in stroke+CKD animals as compared to sham, stroke and CKD. Mitochondrial respiration was compromised in stroke+CKD group as compared to other groups. Increased DRP1, calcineurin and caspase3 levels were observed. Increased brain homocysteine levels were detected in CKD and CKD+Stroke groups by LCMS/MS. Conclusions: Mitochondrial dysfunction following CKD may contribute towards exacerbation of ischemic stroke pathology. Disclosure: Dr. Bhattacharya has nothing to disclose. Shah Vipulkumar has nothing to disclose. Miss Sarmah has nothing to disclose. Aishika Datta has nothing to disclose. Kiran Kalia has nothing to disclose. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson & Johnson. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving as a Consultant for Neural Analytics, Inc. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RAPID MEDICAL LTD.. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Yavagal has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Neural Analytics, Inc. Dr. Yavagal has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Carnival Cruises. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Royal Carribean Cruises Ltd.. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint Global. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Goldberg Segalla LLP. Dr. Yavagal has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Rourke and Blumenthal, LLP. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Eadie Hill Trial Lawyers. Dr. Yavagal has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Goldberg Segalla LLP.