Compromised blood-brain barrier competence in remote brain areas in ischemic stroke rats at the chronic stage.
Compromised blood-brain barrier competence in remote brain areas in ischemic stroke rats at the chronic stage.
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DOI：
10.1002/cne.23582
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发表时间：
2014-09-01
影响因子：
2.5
通讯作者：
Borlongan, Cesario V.
中科院分区：
文献类型：
--
作者：
Garbuzova-Davis, Svitlana;Haller, Edward;Williams, Stephanie N.;Haim, Eithan D.;Tajiri, Naoki;Hernandez-Ontiveros, Diana G.;Frisina-Deyo, Aric;Boffeli, Sean M.;Sanberg, Paul R.;Borlongan, Cesario V.
中风是一种危及生命的疾病，导致中风幸存者长期残疾。慢性脑卒中的脑功能不全可能是由于远离初始缺血性病变的脑区的病理变化，即神经联系不能。以前，我们表明，受损的血脑屏障（BBB）牵连在亚急性神经联系不能。本研究采用短暂性大脑中动脉闭塞（tMCAO）大鼠模型，研究慢性神经功能联系不能时的血脑屏障功能。我们的研究结果表明，在tMCAO后30天，大鼠的同侧纹状体和运动皮质中存在显著的BBB损伤。通过超微结构和免疫组织化学分析，还确定了对侧半球的BBB改变。对侧远端纹状体和运动皮质区的主要BBB病理变化包括：（1）空泡化的内皮细胞含有大的自噬体，（2）变性的周细胞显示线粒体伴嵴断裂，（3）变性的星形胶质细胞和血管周围水肿，（4）伊文思蓝外渗，（5）出现实质星形胶质细胞增生。重要的是，纹状体和运动皮质区的离散分析显示，在两个大脑半球的腹侧纹状体和背侧纹状体星形胶质细胞增生的毛细血管中的自噬体积累显着较高。同侧和对侧大脑半球的这些广泛的微血管改变表明慢性缺血中持续和/或持续的BBB损伤。远端脑区的病理变化可能提示慢性缺血性神经功能不能，在制定卒中治疗策略时应予以考虑。
Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke.
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影响因子：
2.9
作者：
Ay, Ilknur;Francis, Jonathan W.;Brown, Robert H., Jr.
通讯作者：
Brown, Robert H., Jr.
影响因子：
8.3
作者：
Borlongan, CV;Hadman, M;Sanberg, PR
通讯作者：
Sanberg, PR
影响因子：
2.9
作者：
BORLONGAN, CV;CAHILL, DW;SANBERG, PR
通讯作者：
SANBERG, PR
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD
DOI：
10.1093/jnen/62.4.329
发表时间：
2003-04-01
影响因子：
3.2
作者：
Ferrer, I;Planas, AM
通讯作者：
Planas, AM