Garbuzova-Davis Svitlana, Haller Edward, Tajiri Naoki, Thomson Avery, Barretta Jennifer, Williams Stephanie N, Haim Eithan D, Qin Hua, Frisina-Deyo Aric, Abraham Jerry V, Sanberg Paul R, Van Loveren Harry, Borlongan Cesario V
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
J Neuropathol Exp Neurol. 2016 Jul;75(7):673-88. doi: 10.1093/jnen/nlw040. Epub 2016 Jun 9.
We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction.
我们先前证明，在短暂性大脑中动脉闭塞（tMCAO）后7天和30天，大鼠对侧远隔脑区存在血脑屏障损伤，提示存在缺血性神经机能联系障碍。在此，我们聚焦于亚急性和慢性局灶性脑缺血对血脊髓屏障（BSCB）的影响。我们观察到，tMCAO后7天和30天，大鼠颈髓两侧均存在BSCB损伤。脊髓灰质和白质中BSCB的主要超微结构变化包括含有自噬体的空泡化内皮细胞、线粒体肿大的周细胞变性、星形胶质细胞终足变性和血管周围水肿；还观察到运动神经元受损、升支和降支中轴突肿胀伴髓鞘松解以及星形胶质细胞增生。伊文思蓝染料外渗在7天时达到最大值。免疫荧光证据显示，缺血后7天紧密连接蛋白occludin的微血管表达减少、Beclin-1和LC3B免疫反应性上调，而在30天时后者减少。tMCAO后大鼠颈髓微血管的这些新的病理改变提示，局灶性脑缺血后存在广泛且持久的BSCB损伤，并且在缺血性脑梗死患者的病理生理学和治疗方法中应考虑脊髓缺血性神经机能联系障碍。
