Imbalance of thalamic metabolites in an experimental model of hypertension: role of bergamot polyphenols

Abstract

Abstract Funding Acknowledgements None. Hypertension is emerging as a pathogenic factor in vascular-based cognitive impairment, altering the structure and function of cerebral vasculature, and representing the main risk factor for cerebral small vessel diseases and neuronal loss. Some studies correlated a reduction in regional cerebral blood flow in the thalamus of elderly hypertensive brains with the decrease in certain cerebral metabolites, because of hypoperfusion. Patients with severe hypertension show a reduced oxygen consumption in regions with reduced cerebral blood flow suggesting that, the vascular dysfunction and the reduced cerebral blood flow could be related to reduced metabolic demands due to brain dysfunction and damage. Chronic cerebral hypoperfusion is associated with increased inflammatory state and oxidative stress. Herein, we hypothesized to prevent or reduce the onset of oxidative stress using natural occurring antioxidant compounds could be of particular importance for the management of hypertension-induced cerebral complications. Hypertension was induced on Wistar male rats by left renal artery ligation (RAL). After complete recovery from surgery, the animals were treated with 20 mg/kg deoxycorticosterone acetate twice a week for 4 weeks, and 1% sodium chloride (NaCl) water. A subgroup of hypertensive rats received Bergamot Polyphenolic Fraction (BPF) by gavage. A control group was treated with sub-cutaneous injection of saline. At baseline (T0), after 2 weeks (T1) and at the end of the experimental period (T2), the thalamic neurochemical profile were evaluated using proton magnetic resonance spectroscopy (1H-MRS), performed with a Bruker Pharmascan 70/16 7T. VAPOR water-suppression module was used and optimized to reduce residual water, then thalamic spectra were acquired using a short echo time single voxel point-resolved spectroscopy technique (voxel size 3x3x3 mm). The absolute quantification of metabolite concentrations has been performed using TARQUIN (v.4.3.10). A reduction tending to significance of the tNAA/tCr ratio, emerged in the thalamus of RAL DOCA-Salt rats compared to control rats at T2. A significant reduction of the tNAA/tCr ratio was observed in the group of RAL DOCA-Salt rats at the T2 compared to the same animals at the T1. In addition, a significantly decrease of the tCho/tCr ratio was highlighted in the RAL DOCA-Salt animals compared to the CTRL rats starting from the T1. The administration of BPF ameliorates the tNAA/tCr ratios in the thalamus of RAL DOCA-Salt rats. Such evidence of the influence of hypertension on tNAA/tCr and tCho/tCr ratios could better explain the relationship between brain structure and modulation of some metabolites, providing new insights into hypertension-induced brain complications and the contribution that the use of natural compounds could give to their management.