Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia
Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia
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DOI：
10.1186/s40478-020-01009-1
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发表时间：
2020-08-08
影响因子：
7.1
通讯作者：
Carare, Roxana O.
中科院分区：
文献类型：
--
作者：
Sharp, Matthew MacGregor;Saito, Satoshi;Carare, Roxana O.
白色高信号（WMH）与痴呆相关，但病因尚不清楚。在这里，我们测试的假设，有一个受损的消除间质液从白色的问题连同一定程度的缺氧在WMH的组合。β淀粉样蛋白（A β）从大脑中消除的机制之一是沿着毛细血管和动脉壁中的基底膜（动脉壁内引流- iPad）。我们通过注射可溶性A β作为示踪剂，比较了10周龄C57/B16小鼠海马灰质和胼胝体白色物质中iPad的动态。与灰质相比，白色物质中iPad的动力学明显较慢，这与白色物质中毛细血管密度较低有关。将平滑肌细胞培养物暴露于高碳酸血症作为脑灌注不足的模型导致细胞外基质中纤连蛋白减少和层粘连蛋白增加。在人WMH的白色物质中检测到类似的变化，表明高碳酸血症/缺氧可能在WMH中起作用。采用增强iPad和白色物质中血流的疗法可能会降低痴呆患者的WMH。
White matter hyperintensities (WMH) occur in association with dementia but the aetiology is unclear. Here we test the hypothesis that there is a combination of impaired elimination of interstitial fluid from the white matter together with a degree of hypoxia in WMH. One of the mechanisms for the elimination of amyloid-beta (A beta) from the brain is along the basement membranes in the walls of capillaries and arteries (Intramural Peri-Arterial Drainage - IPAD). We compared the dynamics of IPAD in the grey matter of the hippocampus and in the white matter of the corpus callosum in 10 week old C57/B16 mice by injecting soluble A beta as a tracer. The dynamics of IPAD in the white matter were significantly slower compared with the grey matter and this was associated with a lower density of capillaries in the white matter. Exposing cultures of smooth muscle cells to hypercapnia as a model of cerebral hypoperfusion resulted in a reduction in fibronectin and an increase in laminin in the extracellular matrix. Similar changes were detected in the white matter in human WMH suggesting that hypercapnia/hypoxia may play a role in WMH. Employing therapies to enhance both IPAD and blood flow in the white matter may reduce WMH in patients with dementia.