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-β (Aβ) 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 Aβ 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.

中文翻译：

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在与年龄和痴呆症相关的白质高信号区域显示出从脑白质和缺氧中去除液体的能力降低。

白质过高症（WMH）与痴呆症有关，但病因尚不清楚。在这里，我们测试了以下假设：WMH中白质中的组织液清除能力降低以及缺氧程度相结合。从大脑中消除淀粉样β（Aβ）的机制之一是沿着毛细血管和动脉壁的基底膜（壁内动脉周围引流– IPAD）。我们通过注射可溶性Aβ作为示踪剂，比较了10周龄C57 / B16小鼠海马灰质和call体白质IPAD的动力学。与灰质相比，白质中IPAD的动力学要慢得多，这与白质中较低的毛细管密度有关。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，导致纤连蛋白减少，而细胞外基质中层粘连蛋白增加。在人类WMH中的白质中检测到类似的变化，提示高碳酸血症/低氧可能在WMH中起作用。在痴呆症患者中采用增加IPAD和白质血流量的疗法可能会降低WMH。