Daily blood pressure profile and blood–brain barrier permeability in patients with cerebral small vessel disease

Abstract

Cerebral small vessel disease (CSVD) plays an important role in cognitive impairment, stroke, disability, and death. Hypertension is the main risk factor for CSVD. The use of antihypertensive therapy has not resulted in the expected decrease in CSVD complications, which may be related to the underestimation of significance of daily blood pressure profile for blood–brain barrier (BBB) permeability. 53 patients with CSVD of varying severity (mean age 60.08 ± 6.8 years, 69.8% women, subjects with treated long-standing hypertension vs. normotensive subjects − 84.8% vs. 15.2%) and 17 healthy volunteers underwent ambulatory blood pressure monitoring (ABPM) and MRI, including T1-weighted dynamic contrast-enhanced magnetic resonance imaging for assessing BBB permeability. Most of ABPM parameters in CSVD patients did not differ from controls, but were associated with the severity of white matter hyperintensity (WMH) and the total CSVD score. BBB permeability in normal-appearing white matter (NAWM) and grey matter (GM) was significantly higher in CSVD patients, and the severity of BBB permeability remained similar in patients with different stages of WMH. Among BBB permeability parameters, the area under the curve, corresponding to an increase in the contrast transit time in NAWM, had the greatest number of correlations with deviations of ABPM parameters. BBB permeability in CSVD is a universal mechanism of NAWM and GM damage associated with a slight increase in ABPM parameters. It is obvious that the treatment of hypertension in patients with not severe WMH should be more aggressive and carried out under the control of ABPM.

Cerebral small vessel disease: a bibliometric analysis

“…A large area of necrosis can be seen in the left hemisphere, including the presence of neuro brillary tangles and amyloid plaques in the hippocampus and frequent amyloid plaques in the cerebral cortex, thickening of arterial walls, perivascular spaces are also found Enlargement, arteriosclerosis, microbleeds, and white matter thinning are consistent with features of CSVD and underscore the importance of the gut-vagus-brain axis in late-onset post-stroke dementia(Jiaerken et al, 2021). Furthermore, age-and hypertension-related cerebral small vessel disease are also major determinants of cognitive decline and disability in the elderly(Dobrynina et al, 2022;Goldstein et al, 2022).At present, treatment measures are mainly based on the characteristics of risk factors, the type and severity of biomarkers, and the severity of clinical sequelae. In clinical practice, blood pressure lowering, thrombolysis, and antiplatelet therapy are mostly used(Arba et al, 2019;Pan et al, 2022;Du H et al, 2022).…”

Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension

“…54,55 In humans, BBB breakdown is an early biomarker of cognitive impairment, 56 specifically BBB breakdown in the hippocampus worsened mild cognitive impairment. 57 Although BBB disruption is present in some patients with hypertension 58 and may be associated with changes in daily blood pressure profile, 59 it has not been widely reported as a key feature of hypertension. Whether this is a result of the difficulty to evaluate the effect of hypertension in the presence of other comorbidities, or a true indication of the low prevalence of BBB disruption in the human patient population remains to be determined.…”

Blood–Brain Barrier Disruption and Perivascular Spaces in Small Vessel Disease and Neurodegenerative Diseases: A Review on MRI Methods and Insights

“…71 The BBB permeability parameters from DCE MRI have been found to correlate to ambulatory blood pressure measures in healthy subjects and cSVD patients with antihypertensive therapy. 72 Studies on patients with MCI found no relation between cardiovascular risk factors and BBB disruption. 73,74 The effect of cardiovascular risk factors on the water exchange rate measured by ASL is somewhat controversial.…”

“…15 Hypertension and increased arterial blood pulsatility are considered to cause BBB impairment by inducing extreme forces on the endothelial cells and tight junctions (mechanotransduction), thereby damaging the physical BBB. 72 Meanwhile, the increased blood pulsatility in hypertension may also cause enlargement of the arterial PVS by damaging the surrounding tissue and by increasing vessel tortuosity. 95 Age is the other common underlying risk factor that is related to both BBB disruption 70,71 and enlargement of PVS.…”