Abstract 16785: Hypertension Induces Metabolite Content Alterations in Hypoperfused Mouse Brain Cortex

Abstract

Introduction and aims: Hypertension is one of the main risk factors for dementias. To understand the link between vasculature and neuronal dysfunction in hypertension-induced cognitive impairment we leverage MRI, a translational imaging tool that let us concomitantly analyze cerebral structure, function and metabolism. Methods: Transverse aortic constriction (TAC) was performed in C57Bl/6J mice to induce cerebral hypertension. The brain was characterized by structural MRI, cerebral blood flow (CBF) was analyzed by perfusion MRI and cortical cerebral metabolism was characterized by point-resolved spectroscopy performed on a small-animal dedicated 7T MRI. Finally, we characterized the microvascular structure in regions impacted by hypertension by immunofluorescence. Results: TAC mice shown hemodynamic alterations in cortical CBF compared to sham mice (A). Macroscopic volumetric analyses of the cortex shown no significant alterations, however hypoperfused cortical regions shown local cortical thickening, suggesting a local swelling due to inflammatory processes (B). The histological microvascular analysis evidenced capillary Blood-Brain Barrier loss of integrity (C). Finally, this cortical region shown alterations in glucose and glutamine metabolite concentration measured by MR spectroscopy (D). Conclusions: Leveraging MRI we have concomitantly characterized the cortical structure, function and metabolism in TAC-hypertensive mice. These alterations in cerebral blood flow and metabolism of glucose/glutamine are biomarkers of ongoing cerebral injury and are potential targets of further investigation to shed light on the interplay between vascular and neuronal injury in hypertension.