Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?
Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?
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DOI：
10.1161/01.str.0000058480.77236.b3
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发表时间：
2003-03-01
期刊：
影响因子：
8.3
通讯作者：
Starr, J
中科院分区：
文献类型：
--
作者：
Wardlaw, JM;Sandercock, PAG;Starr, J
背景：小的深部（腔隙）梗死、脑白质疾病（白质变病或白质高信号）和进行性认知障碍或痴呆的发病机制和关系尚存争议。我们假设脑小血管内皮（即血脑屏障）功能障碍，血浆成分渗漏到血管壁和周围脑组织导致神经元损伤，可能导致3种重叠和致残性脑血管疾病的发展：腔隙性卒中、白质变病和痴呆。这一假说可以解释缺血性脑血管病与几种明显不同的临床痴呆综合征之间的联系。这一假设得到了腔隙性卒中和白质变的病理、流行病学和实验研究以及MRI对血脑屏障的观察的支持。我们怀疑，血脑屏障功能障碍的潜在意义，作为一个致病步骤，连接血管疾病与常见的，致残性脑疾病的潜伏发作已被忽视。例如，脂透明质沉积症，其病理表现来源不明，可能导致一些离散腔隙性梗死，可能是临床表现为血脑屏障功能障碍的疾病谱系的一端。结论：证明血脑屏障失效是这些疾病的关键，可以为新的治疗方法提供靶点，以减少血管疾病对大脑的影响，防止认知能力下降和痴呆。
Background-The pathogenesis of and relationship between small deep (lacunar) infarcts, cerebral white matter disease (leukoaraiosis or white matter hyperintensities), and progressive cognitive impairment or dementia are much debated.Summary of Comment-We hypothesize that cerebral small-vessel endothelial (ie, blood-brain barrier) dysfunction, with leakage of plasma components into the vessel wall and surrounding brain tissue leading to neuronal damage, may contribute to the development of 3 overlapping and disabling cerebrovascular conditions: lacunar stroke, leukoaraiosis, and dementia. This hypothesis could explain the link between ischemic cerebral small-vessel disease and several apparently clinically distinct dementia syndromes. This hypothesis is supported by pathological, epidemiological, and experimental studies in lacunar stroke and leukoaraiosis and observations on the blood-brain barrier with MRI. We suspect that the potential significance of blood-brain barrier failure as a pathogenetic step linking vascular disease with common, disabling brain diseases of insidious onset has been overlooked. For example, lipohyalinosis, which has a pathological appearance of uncertain origin and is possibly responsible for some discrete lacunar infarcts, may be one end of a clinical spectrum of illness manifested by blood-brain barrier failure.Conclusions-Proof that blood-brain barrier failure is key to these conditions could provide a target for new treatments to reduce the effects of vascular disease on the brain and prevent cognitive decline and dementia.