Postischemic Brain Infiltration of Leukocyte Subpopulations Differs among Murine Permanent and Transient Focal Cerebral Ischemia Models
Postischemic Brain Infiltration of Leukocyte Subpopulations Differs among Murine Permanent and Transient Focal Cerebral Ischemia Models
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DOI：
10.1111/j.1750-3639.2012.00614.x
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发表时间：
2013-01-01
期刊：
影响因子：
6.4
通讯作者：
Veltkamp, Roland
中科院分区：
文献类型：
--
作者：
Zhou, Wei;Liesz, Arthur;Veltkamp, Roland
细胞和体液炎症在缺血性脑损伤中发挥重要作用。免疫调节疗法的有效性可能很大程度上取决于所选的实验模型。我们的目的是比较小鼠永久性和暂时性大脑中动脉闭塞（MCAO）模型的缺血后神经炎症。 C57BL/6小鼠经颞叶电凝诱导永久性MCAO，管腔内丝诱导30分钟或90分钟短暂性MCAO。通过免疫组织化学和荧光激活细胞分选来量化白细胞亚群的浸润。通过实时聚合酶链反应（RT-PCR）测量脑细胞因子和粘附分子的表达。短暂性 MCAO 后 24 小时注意到中性粒细胞浸润，但在永久性 MCAO 模型中直到 5 天才进一步增加。 24 小时时，两种 MCAO 模型中都观察到很少的 T 细胞，但永久性 MCAO 在 5 天时表现出更多的浸润性 T 细胞。显着的小胶质细胞激活在永久 MCAO 后 24 小时和 5 天时明显，但在短暂 MCAO 后则不明显。入侵的 NK 细胞数量和 CD11b+ 细胞上 MHCII 的表达在三组之间没有差异。 MCAO后5天,IL-1、TNF-a、IFN-γ的表达情况永久性 MCAO 组中粘附分子 ICAM-1 和 VCAM-1 的含量显着高于短暂性 MCAO 组。常用的 MCAO 模型中的细胞和体液炎症有很大不同。与 30 分钟和 90 分钟丝状 MCAO 相比，永久性电凝 MCAO 后神经炎症更加明显。
Cellular and humoral inflammations play important roles in ischemic brain injury. The effectiveness of immunomodulatory therapies may critically depend on the chosen experimental model. Our purpose was to compare the post-ischemic neuroinflammation among murine permanent and transient middle cerebral artery occlusion (MCAO) models. Permanent MCAO was induced by transtemporal electrocoagulation and 30?minutes or 90?minutes transient MCAO was induced by intraluminal filament in C57BL/6 mice. Infiltration of leukocyte subpopulations was quantified by immunohistochemistry and fluorescence-activated cell sorting. Cerebral cytokine and adhesion molecule expression was measured by real-time polymerase chain reaction (RT-PCR). Neutrophil infiltration was noted at 24?h after transient MCAO, but did not further increase until 5 days in the permanent MCAO model. Few T cells were observed in both MCAO models at 24?h, but permanent MCAO demonstrated much more infiltrating T cells at 5 days. Pronounced microglial activation was evident at 24?h and 5 days after permanent but not after transient MCAO. The number of invading NK cells and expression of MHCII on CD11b+ cells did not differ among the three groups. Five days after MCAO, the expression of IL-1, TNF-a and IFN-? and of the adhesion molecules ICAM-1 and VCAM-1 was significantly higher in the permanent than in the transient MCAO groups. Cellular and humoral inflammation differs substantially among commonly used MCAO models. Neuroinflammation is more pronounced after permanent electrocoagulatory MCAO compared with 30?minutes and 90?minutes filament-MCAO.