Year: 2025
Type: editorial
Abstract: ypertension affects nearly half of adults in the United States, with its global prevalence rising most rapidly in low-and middle-income countries.Uncontrolled hypertension substantially increases the risk of brain damage, making it one of the most important modifiable cardiovascular risk factors for all-cause dementia.1 Several studies have shown the beneficial effect of controlling blood pressure when it comes to the risk of dementia.2,3 Yet, hypertension remains difficult to manage with ∼40% of patients living with uncontrolled blood pressure despite available therapies.This underscores the urgent need to uncover novel mechanisms of disease progression that could inform the next generation of targeted pharmacotherapies.Long before irreversible brain injury occurs, the cerebral microvasculature undergoes critical molecular and cellular changes that may represent a therapeutic window.Particularly, cerebral small vessel disease (cSVD) is a key contributor to cognitive decline in hypertension.Although hypertension alone increases the risk of dementia, cSVD is particularly impactful as it is strongly associated with cognitive decline, mood disturbances, and balance problems and contributes to ∼25% of ischemic strokes. 1 Among imaging markers used to diagnose cSVD, white matter hyperintensities, cerebral microbleeds (CMBs), and enlarged perivascular spaces are most prominent in hypertension.1 In this study, Arndt et al. 4 used stroke-prone spontaneously hypertensive rats (SHRSP) that develop both CMBs and enlarged perivascular spaces alongside high blood pressure and cognitive decline to better understand how the length of hypertension affects brain health.The SHRSP model was chosen because these animals reliably develop hypertension and cSVD without additional interventions, making them relevant for modeling vulnerable patients in the early and preclinical stages of disease.The authors approached hypertension as a continuum and characterized molecular and cellular events driving disease progression, offering insights into when and how interventions might be most effective.Focusing on the frontal cortex, a region that is particularly vulnerable in patients with hypertension across multiple modalities, including cognitive testing, gene expression studies, and neuroimaging, the authors dissected temporal mechanisms across distinct stages of hypertension (Figure ): initial (6-8 weeks old), early chronic (14-15 weeks old), and late chronic (32-34 weeks old) hypertension.Wistar controls at each stage allow for separating the effects of aging versus hypertension length.Of note, the rats studied in both early and late chronic hypertension groups were stroke-free.Because 70% to 80% of SHRSP develop stroke by 9 months, 5,6 the findings at each time point may reflect distinct disease trajectories.Namely, many rats in the "initial" hypertension group will later develop a stroke, whereas those in the "late chronic" group
Authors: Ismary Blanco, Monica M. Santisteban
Institution: Vanderbilt University Medical Center
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,810
OpenAlex ID: W4416721912