White matter damage is associated with matrix metalloproteinases in vascular dementia
White matter damage is associated with matrix metalloproteinases in vascular dementia
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DOI：
10.1161/01.str.32.5.1162
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发表时间：
2001-05-01
期刊：
影响因子：
8.3
通讯作者：
Esiri, MM
中科院分区：
文献类型：
--
作者：
Rosenberg, GA;Sullivan, N;Esiri, MM
背景和目的-血管疾病导致多梗死性痴呆(MID)或Binswanger病(BD)，后者是血管性痴呆(VAD)的进行性形式，病理上与脑小动脉纤维蛋白和透明质改变有关，并伴有脑白质损伤。临床上，ED患者长期存在高血压，并伴有步态和智力障碍。由于基质金属蛋白酶(MMPs)在脑梗塞中起重要作用，我们推测VAD可能与MMPs的紊乱有关。方法：对5例血管性痴呆和多发性梗死型(MID)患者的脑组织进行胶质纤维酸性蛋白、小胶质细胞/巨噬细胞标记物(PG-MI)、明胶酶A(MMP2)、基质分解酶L(MMP3)和明胶酶B(MMP9)的免疫组织化学染色。对照组织来自8例老年患者：4例非痴呆性卒中患者和4例非神经系统疾病患者。结果卒中非痴呆组和VaD组梗死灶周围均可见PG-M1+细胞。在3例ED患者中，2例PC-Mi细胞位于受损小动脉附近，弥漫分布于白质内。MMP2在血管周围巨噬细胞和血管附近的星形细胞突起中正常表达，并存在于反应性星形胶质细胞中的卒中患者。少见基质金属蛋白酶-9的表达。急性梗死灶周围PG-MIS微胶质/巨噬细胞表达基质金属蛋白酶-3。在ED患者中，MMP3持续存在于组织巨噬细胞中，在长期存在的白质胶质细胞中消失。结论：MMPs可能参与了VAD相关白质的损伤。小胶质细胞/巨噬细胞诱导的损伤是VaD进行性发展的一个因素，这种损伤是可以治疗的。
Background and Purpose-Vascular disease causes multi-infarct dementia (MID) or Binswanger's disease (BD), the latter of which is a progressive form of vascular dementia (VaD) associated pathologically with fibrinoid and hyaline changes in brain arterioles with injury to the white matter. Clinically, ED patients have long-standing hypertension with disturbances of gait and intellect. Because matrix metalloproteinases (MMPs) are important in cerebral infarction, we hypothesized that disturbances in the MMPs may be involved in VaD.Methods-Brain tissues from 5 patients with VaD of the ED or multi-infarct type (MID) were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a microglial/macrophage cell marker (PG-MI), gelatinase A (MMP-2), stromelysin-l (MMP-3), and gelatinase B (MMP-9). Control tissues were from 8 elderly patients: 4 with strokes without dementia and 4 without neurological diseases.Results-PG-M1+ cells appeared around infarct in patients with strokes without dementia and in patients with VaD. In 2 of the 3 ED patients, PC-Mi cells were prominent near damaged arterioles and scattered diffusely in white matter. MMP-2 was seen normally in perivascular macrophages and in astrocytic processes near blood vessels and was present in patients with strokes in reactive astrocytes. MMP-9 was rarely seen. MMP-3 was seen in PG-MIS microglial/macrophage cells around the acute infarctions. In ED, MMP-3 persisted in tissue macrophages and disappeared in long-standing white matter gliosis.Conclusions-These observations suggest that MMPs may participate in the damage to the white matter associated with VaD. Microglia/macrophage-induced damage, which is amenable to treatment, may be a factor in the progressive forms of VaD.