Injury to axons and oligodendrocytes following endothelin-1-induced middle cerebral artery occlusion in conscious rats
Injury to axons and oligodendrocytes following endothelin-1-induced middle cerebral artery occlusion in conscious rats
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DOI：
10.1016/j.brainres.2006.06.111
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发表时间：
2006-09-19
期刊：
影响因子：
2.9
通讯作者：
Callaway, Jennifer K.
中科院分区：
文献类型：
--
作者：
Gresle, Melissa M.;Jarrott, Bevyn;Callaway, Jennifer K.
在大多数中风动物模型中，轴突和少突胶质细胞损伤的特征尚不清楚，因此很难进行靶向治疗。因此，有必要表征这些模型中的轴突和少突胶质细胞损伤，以便合理设计假定的保护性化合物，最大限度地减少这种损伤。本研究旨在表征清醒大鼠大脑中动脉闭塞 (MCAO) 内皮素-1 (ET-1) 模型中轴突和少突胶质细胞的损伤。通过血管周围显微注射 ET-1，在清醒的成年雄性 Long Evans 大鼠中诱导短暂性前脑缺血。在 ET-1 给药后 6、24、48 和 72 小时，使用弹道光分析和免疫组织化学对淀粉样前体蛋白 (APP)、SMI32 和 Tau-1 对前脑切片进行定量组织病理学分析。对皮质和纹状体病变的弹道光分析显示，这些区域的梗塞体积在 6 小时内达到最大。 APP 和 SMI32 免疫组织化学证明该模型中轴突损伤在 6 小时时达到最大；然而，一些受伤的轴突似乎在损伤后 72 小时内仍保持良好的结构完整性。从 48 小时起，胼胝体内 Tau-1 免疫阳性少突胶质细胞的密度测量值显着升高，但注射 ET-1 后 72 小时，少突胶质细胞总数的减少并不明显。这些结果表明，轴突和少突胶质细胞损伤应作为 MCAO 后延迟治疗干预的潜在目标进行研究。 (c) 2006 Elsevier B.V. 保留所有权利。
Injury to axons and oligodendrocytes has been poorly characterized in most animal models of stroke, and hence has been difficult to target therapeutically. It is therefore necessary to characterize axonal and oligodendroglial injury in these models, in order to rationally design putative protective compounds that minimize this injury. This study aims to characterize injury to axons and oligodendrocytes in the endothelin-1 (ET-1) model of middle cerebral artery occlusion (MCAO) in conscious rats. Transient forebrain ischemia was induced in conscious adult male Long Evans rats by the perivascular microinjection of ET-1. Quantitative histopathology was performed on forebrain sections at 6, 24, 48 and 72h after ET-1 administration, using ballistic light analyses and immunohistochemistry for amyloid precursor protein (APP), SMI32, and Tau-1. Ballistic light analyses of cortical and striatal lesions revealed that the infarct volume was maximal in these regions by 6h. APP and SMI32 immunohistochemistry demonstrated that axonal injury was maximal by 6h in this model; however, some injured axons appeared to maintain good structural integrity up to 72h after insult. Density measurements for Tau-1-immunopositive oligodendrocytes were significantly elevated within the corpus callosum from 48h, but reductions in total oligodendrocyte numbers were not apparent up 72h after ET-1 injection. These results indicate that axonal and oligodendroglial injury should be investigated as potential targets for delayed therapeutic intervention after MCAO. (c) 2006 Elsevier B.V. All rights reserved.