Abstract WP421: Remote Ischemic Injury Mediates Hippocampal Astrocytic Endfeet Remodeling, Increases Vascular Injury and Worsens Cognitive Deficits in Diabetes

Abstract

Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. We showed pathological rearrangement of cerebrovascular networks in the cortex and striatum is associated with poor neuronal restoration leading to worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on vascular architecture of hippocampus, a domain critical to memory and learning. We hypothesized that diabetes would mediate vasoneuronal remodeling and exacerbate post-stroke deficits in hippocampal tasks. Diabetes was induced by a high fat diet and low dose STZ in male Wistar rats. Cognition was assessed for 2 weeks after stroke (90-min middle cerebral artery occlusion MCAO) by Novel Object Recognition (NOR) and Placement (NPR), Y-Maze and Social Recognition tests. Vasoneuronal architecture and integrity were assessed by measurement of surface area, branch density, IgG extravasation, neuron counts and aquaporin4 (AQP4) polarity for astrocytic endfeet remodeling in dentate gyrus. Diabetes alone increased BBB permeability and unpolarized AQP4, which were exacerbated after MCAO. Post-stroke branch density was higher in control but lower in diabetic rats. While lower baseline hippocampal neuron counts in diabetes was not further reduced after MCAO, poor baseline cognitive and social performance deteriorated. These results suggest that remote ischemic injury can induce profound vasoglial remodeling in the hippocampus and worsens functional outcomes without reducing neurons. Understanding how diabetes impacts post-stroke neurovascular recovery in hippocampus may provide critical insight to worsened cognitive outcomes in this population.