Abstract W P412: Metabolic Syndrome Alters Cerebrovascular Architecture: Relevance to Cognitive Deficits and Stroke Outcomes

Abstract

Introduction: Diet-induced metabolic syndrome (MetS) is an increasing risk factor for stroke. We have previously shown that high fat diet 1) increases infarct size and hemorrhagic transformation and worsens functional outcome after stroke and 2) impairs neurovascular function even before stroke. However, the impact of MetS on cerebrovascular architecture remained unknown. Hypotheses: 1) Diet-induced MetS causes pathological neovascularization; and 2) these changes lead to cognitive deficits at baseline and poor recovery after stroke. Methods: Male Wistar rats were given a control diet or low dose streptozotocin (30mg/kg) plus high fat (45%) diet for a period of eight weeks (n=4-8/group). Animals were then subjected to sham or middle cerebral artery occlusion (MCAO) surgery. Motor and cognitive functions were assessed by at Days 1, 3, 10 and 14 after stroke using Bederson’s Score, Beam Walking Test, and Novel Object Recognition. Vascular indices (branch density, tortuosity, vascular volume and surface area) were then measured in cortex and striatum using confocal imaging of FITC-filled vasculature. Results: Branch density was higher and recognition index was lower in the sham MetS group compared to sham control group. Stroke significantly reduced vascular volume and surface area in both groups, which was more prominent in the MetS group. Branch density was increased after stroke in the control group only. At Day 14, motor and cognitive scores in the sham MetS group were lower than control. Conclusion: Cerebrovascular structure, function, and cognition are impaired from diet-induced MetS alone . Collectively, these data suggest that cerebrovasculature is an early target in MetS and vasculoprotective strategies are needed to prevent cerebral complications.