Center of Excellence for Aging & Brain Repair, University of South Florida, Morsani College of Medicine, Tampa, Florida, United States of America.
PLoS One. 2013 May 10;8(5):e63553. doi: 10.1371/journal.pone.0063553. Print 2013.
Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas.
METHODOLOGY/PRINCIPAL FINDINGS: In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices.
CONCLUSIONS/SIGNIFICANCE: These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.
全面的中风研究揭示了远隔失联络现象，即由于远离初始缺血性损伤的脑区存在病理性缺陷而导致的功能丧失。然而，亚急性期远隔失联络时血脑屏障（BBB）的完整性尚不确定。本研究在局灶性缺血性中风大鼠模型中研究了亚急性期远隔失联络现象。具体关注点是对侧大脑区域的 BBB 完整性及相关致病过程。
方法/主要发现：在短暂性大脑中动脉闭塞（tMCAO）后 7 天的同侧半球中，在纹状体、运动和体感皮质中检测到明显的 BBB 改变，特征为 Evans Blue（EB）实质外渗、自噬体堆积、反应性星形胶质细胞和激活的小胶质细胞增加、脱髓鞘和神经元损伤。超微结构和免疫组织化学分析也发现了对侧半球的血管损伤。在对侧纹状体和运动皮质中，主要的超微结构 BBB 改变包括：含有大量自噬体的肿胀和空泡化的内皮细胞、周细胞变性和血管周围水肿。此外，在对侧纹状体和运动及体感皮质中还观察到明显的 EB 外渗、内皮自噬体形成增加、弥漫性星形胶质细胞增生、激活的小胶质细胞、广泛的神经元固缩和髓鞘减少。
结论/意义：这些结果表明，局灶性缺血性中风不仅引起同侧，而且引起对侧大脑区域的病理紊乱，这与远隔脑微血管的 BBB 破裂和内皮自噬体堆积密切相关。亚急性期的这种微血管损伤可能揭示了缺血性远隔失联络现象，在开发中风治疗策略时应加以考虑。
