Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model

Experimental & Translational Stroke Medicine

Holger Braun¹  Cornelia Garz²  Celine Zoe Bueche²  Stefanie Schreiber¹ 

[1] German Center for Neurodegenerative Diseases (DZNE), Brenneckestrasse 6, Magdeburg, 39118, Germany;Department of Neurology, Otto-von-Guericke-University, Leipziger Strasse 44, Magdeburg, 39120, Germany

关键词: SHRSP;    Cerebral small vessel disease;    Cerebral microbleeds;    Blood brain barrier;    Animal model;   

Others  :  861636
DOI  :  10.1186/2040-7378-5-4

 received in 2013-02-17, accepted in 2013-03-05,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Schreiber et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

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