Authors: Lorenzo Carnevale, Raimondo Carnevale, Marialuisa Perrotta, Francesco Mastroiacovo, Daniela Carnevale, Giuseppe Lembo
Published: 2023-06-15
DOI: 10.1161/circ.146.suppl_1.15180
Source: Full article
While several works pointed out the epidemiological associations between hypertension and dementia, the underlying mechanisms are still relatively unknown. In this work we focused on the application of translational tools like MRI to investigate the brain injury induced by hypertension and characterized by cognitive impairment and neuroinflammation. Cerebral hypertension was induced in mice by transverse aortic constriction (TAC) or sham procedure, as previously demonstrated by our group. We characterized cerebral blood flow (CBF) by 7T MRI, measuring the cerebral tissue blood prefusion. Morris Water Maze (MWM) was used to evaluate cognitive function in hypertensive and normotensive mice. Cortical microvasculature was analyzed in histological brain sections. A group of mice was treated with an antibody neutralizing IFNy, a key proinflammatory cytokine induced by hypertension. TAC mice showed a marked cerebral hypoperfusion, with CBF reduction in cortex (Sham: 96.58 vs TAC: 74.25 mL/100g/min p=0.024) and hypothalamus (Sham: 140 vs TAC: 121.4 mL/100g/min p=0.027). Tissue analysis revealed a reduction in capillary density defined as portion of field of view (FOV) occupied by capillaries (Sham: 11.3% vs TAC: 7.7%, p=0.004) and loss of their integrity in the cortex of hypertensive mice, defined as pericyte coverage percentage in the FOV (Sham: 79% vs TAC: 36%, p=0.01). Finally, the impairment in cognitive function measured by the MWM correlated with the CBF measures (r