Freeze Whitney M, Jacobs Heidi I L, Schreuder Floris H B M, van Oostenbrugge Robert J, Backes Walter H, Verhey Frans R, Klijn Catharina J M
Department of Psychiatry & Neuropsychology, Alzheimer Center Limburg, School for Mental Health & Neuroscience, Maastricht University, Maastricht, Netherlands.
Department of Radiology & Nuclear Medicine, School for Mental Health & Neuroscience, Maastricht University Medical Center, Maastricht, Netherlands.
Front Neurol. 2018 Nov 12;9:926. doi: 10.3389/fneur.2018.00926. eCollection 2018.
Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-brain barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease. We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-brain barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds. Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-brain barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage ( = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage ( = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage ( = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology ( = 489) found indications for blood-brain barrier dysfunction. One study in hypertensive vasculopathy-related intracerebral hemorrhage ( = 82) found no evidence for blood-brain barrier abnormalities. Signs of blood-brain barrier dysfunction were found in 20 out of 26 studies. Blood-brain barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.
高血压性血管病变和脑淀粉样血管病是脑小血管病最常见的两种形式。这两种形式都与原发性脑出血的发生有关，但自发性血管破裂的病理生理机制尚不清楚。这项工作构成了一项关于脑小血管病所致自发性脑出血病因中血脑屏障功能障碍的系统评价。我们检索了Medline（1946 - 2018年）和Embase（1974 - 2018年），以查找关于与脑出血或脑微出血相关的血脑屏障功能障碍的动物和人体研究。在26项符合条件的研究中，10项为动物研究，16项为人体研究。作者发现在所有四项针对高血压性血管病变相关脑出血的动物研究中（四项研究共纳入32只高血压动物）均有血脑屏障功能障碍的迹象，在六项脑淀粉样血管病相关脑出血研究中的四项（共47例）也有该迹象。在人体研究中，六项脑淀粉样血管病相关脑出血患者研究中的五项（共117例）以及九项检查混合性或未明确病因的脑出血研究中的七项（共489例）发现了血脑屏障功能障碍的迹象。一项针对高血压性血管病变相关脑出血的研究（共82例）未发现血脑屏障异常的证据。26项研究中有20项发现了血脑屏障功能障碍的迹象。血脑屏障的完整性值得进一步研究，以期确定自发性脑出血的潜在治疗靶点。
