Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities.
Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities.
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DOI：
10.1186/s40478-022-01497-3
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发表时间：
2023-01-04
影响因子：
7.1
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中科院分区：
文献类型：
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痴呆的主要血管原因是脑小血管病（SVD），包括其中的白色物质高信号（WMH）。虽然SVD的潜在病理学尚不清楚，但慢性高血压和神经炎症被认为是SVD和正常外观白色物质（NAWM）转化为WMH的重要风险因素。不幸的是，大多数研究神经炎症在WMH中的作用的研究依赖于外周血标志物，例如，全身或血管炎症的标志物，作为大脑本身炎症的代表。然而，尚不清楚这些标记物是否准确地捕捉大脑白色物质内的炎症变化。因此，我们的目标是全面研究高血压对WMH和NAWM血管周围和神经炎症的影响。我们进行了高场强脑磁共振成像（MRI），然后对有高血压史的老年人（n = 17）和年龄匹配的正常血压个体（n = 5）的人类死后大脑进行神经炎症标记物的（免疫）组织病理学染色。将MRI图像与（免疫）组织病理学数据（包括小胶质细胞和星形胶质细胞染色）共配准，以评估显微镜分辨率下基于MRI的WMH的变化。根据整个白色物质区域最小血管的血管周围星形胶质细胞增生的严重程度，仔细评估血管周围炎症。在WMH和NAWM中，高血压与更大的炎症反应相关。值得注意的是，在WMH和NAWM中，高血压患者中近距离血管周围炎症的存在是对照组的两倍，表明神经血管炎症在WMH的病因学中至关重要。此外，更高程度的小胶质细胞活化与更高的WMH负荷有关。我们的研究结果表明，神经（血管）炎症在大脑本身的水平是参与WMH的病因。未来的治疗策略侧重于多靶点干预，包括抗高血压治疗以及神经炎症可能会改善WMH进展。在线版本包含补充材料，可通过10.1186/s40478-022-01497-3获得。
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. The online version contains supplementary material available at 10.1186/s40478-022-01497-3.
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DOI：
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