Abstract DP266: Lysosome-Mitochondria Temporal and Spatial Regulation of Zinc Aggregation: A Novel Mechanistic Pathway in Ischemic Stroke

Introduction: Ischemia stroke is the second leading cause of death and disability globally. Mitochondria play a pivotal role in determining ischemia stroke outcomes. We have confirmed that zinc increased immediately after reperfusion in ischemic penumbra of the brain. However, the specific zinc transporters involved and the their mechanisms remain unclear. This study aims to elucidate how zinc accumulation induces post-stroke neuronal mitochondrial dysfunction. Methods: Sprague-Dawley adult rats were subjected to 90 min MCAO. Infarct volume and neurological deficits were determined by TTC staining and scoring systems, and the ischemic penumbra were isolated at 6/24 hours after reperfusion. Zinc levels and mitochondria function (mitochondria complex activity I/II/III/IV and ATP produnction) were measured via ELISA. Zinc transporters, including ZIP family, ZnT family and other zinc transportor (TRPML1) were analyzed by real time PCR, Western blot and immunofluorescence. Results: Zinc levels in ischemic penumbra of the brain were increased 6h after reperfusion (p