Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model.
Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model.
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DOI：
10.1186/2040-7378-5-4
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发表时间：
2013-03-14
期刊：
影响因子：
--
通讯作者：
Braun H
中科院分区：
文献类型：
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作者：
Schreiber S;Bueche CZ;Garz C;Braun H
脑小血管病（CSVD，脑微血管病）可导致痴呆和类似中风的症状。腔隙、白质病变（WML）和微出血是活体影像诊断中所呈现的主要病理相关表现。早期研究将小的穿通脑动脉的节段性动脉壁紊乱描述为腔隙最显著的潜在组织病理学特征。小动脉硬化导致的管腔狭窄被认为会引起白质病变和梗死的灌注不足。
我们利用易卒中型自发性高血压大鼠（SHRSP）模型进行了一项纵向研究，以阐明脑小血管的早期组织学变化。我们认为内皮损伤导致多处血脑屏障（BBB）渗漏，这会对血管壁造成持续性损伤，并最终导致血管破裂和微出血。这些微出血与反应性小血管闭塞一起诱发周围脑实质明显的囊性梗死。因此，多处内皮渗漏部位似乎是脑微血管病的起始点。血管系统对这些早期内皮损伤产生一种激活的凝血状态反应，并由此诱导血流淤滞、红细胞聚集的形成，这是在SHRSP中可检测到的小血管病最早的组织学特征。
在这篇综述中，我们关注血脑屏障破坏在脑小血管病中的意义，并最终讨论对临床医生可能产生的影响。
Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts. We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP. In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians.