Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities

Acta Neuropathologica Communications

Research

Jurgen A. H. R. Claassen¹  Gemma Solé-Guardia²  Arthur de Lange²  Amanda J. Kiliaan²  Maximilian Wiesmann²  Elyne Clijncke²  Bram Geenen²  Emma Custers²  Frank-Erik de Leeuw³  Jose Gutierrez⁴  Benno Küsters⁵ 

[1] Department of Geriatrics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Radboud Alzheimer Center, Nijmegen, The Netherlands;Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands;Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Nijmegen, The Netherlands;Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA;Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands;

关键词: Small vessel disease;    Hypertension;    White matter hyperintensities;    Normal-appearing white matter;    Post-mortem;    Inflammation;   

DOI  :  10.1186/s40478-022-01497-3

 received in 2022-11-09, accepted in 2022-12-19,  发布年份 2022

来源: Springer

【 摘 要 】

The major vascular cause of dementia is cerebral small vessel disease (SVD), including white matter hyperintensities (WMH) amongst others. While the underlying pathology of SVD remains unclear, chronic hypertension and neuroinflammation are recognized as important risk factors for SVD and for the conversion of normal-appearing white matter (NAWM) to WMH. Unfortunately, most studies investigating the role of neuroinflammation in WMH relied on peripheral blood markers, e.g., markers for systemic or vascular inflammation, as a proxy for inflammation in the brain itself. However, it is unknown whether such markers accurately capture inflammatory changes within the cerebral white matter. Therefore, we aimed to comprehensively investigate the impact of hypertension on perivascular- and neuroinflammation in both WMH and NAWM. We conducted high field brain magnetic resonance imaging (MRI), followed by (immuno-)histopathological staining of neuroinflammatory markers on human post-mortem brains of elderly people with a history of hypertension (n = 17) and age-matched normotensive individuals (n = 5). MRI images were co-registered to (immuno-)histopathological data including stainings for microglia and astroglia to assess changes in MRI-based WMH at microscopic resolution. Perivascular inflammation was carefully assessed based on the severity of perivascular astrogliosis of the smallest vessels throughout white matter regions. Hypertension was associated with a larger inflammatory response in both WMH and NAWM. Notably, the presence of close-range perivascular inflammation was twice as common among those with hypertension than in controls both in WMH and NAWM, suggesting that neurovascular inflammation is critical in the etiology of WMH. Moreover, a higher degree of microglial activation was related to a higher burden of WMH. Our results indicate that neuro(vascular)inflammation at the level of the brain itself is involved in the etiology of WMH. Future therapeutic strategies focusing on multitarget interventions including antihypertensive treatment as well as neuroinflammation may ameliorate WMH progression.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

Fig. 1

Fig. 4

Fig. 3