A translational perspective on the interplay between hypertension, inflammation and cognitive impairment

Hypertension represents the major risk factor in the onset of cardiovascular disease worldwide. Preclinically, manifold mouse models of hypertension have been developed to investigate the pathophysiological link between hypertension and vascular impairment. Specifically, Angiotensin-II (Ang II) infusion, transverse aortic constriction (TAC), deoxycorticosterone-acetate (DOCA) - salt, and L-NAME administration as hypertensive stimuli at the preclinical level permit the unveiling of a pro-inflammatory response driven by the innate and adaptive immune system as well leading to vascular injury in terms of structural and functional alterations. Vascular impairment seems to be particularly critical at the cerebral level wherein arterioles, venules, and capillaries finely tune blood supply across the whole brain leading to the onset of a well-known clinical condition named cerebral small vessel disease (cSVD) characterized by extensive brain injury, which culminates in the decline of cognitive functions. Advances in magnetic resonance imaging (MRI) permit identification and accurate diagnosis of specific cSVD biomarkers including white matter hyperintensities (WMHs), lacunar strokes (LS), cerebral microbleeds (CMBs), and enlarged perivascular spaces (ePVSs), each of which proved to be associated with a specific cognitive domain impairment. Such an approach in combination with pharmacological interventions targeted both to the lowering of blood pressure and the prevention of vascular thrombosis formation represents a solid strategy in the prevention and the management of cSVD cognitive decay.