Attenuation of microtubule associated protein-2 degradation after mild head injury by mexiletine and calpain-2 inhibitor
Attenuation of microtubule associated protein-2 degradation after mild head injury by mexiletine and calpain-2 inhibitor
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DOI：
10.1080/02688690701364781
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发表时间：
2007-01-01
影响因子：
1.1
通讯作者：
Cekinmez, M.
中科院分区：
文献类型：
--
作者：
Atalay, B.;Caner, H.;Cekinmez, M.
该研究的目的是解决轻度闭合性头部损伤对神经元稳定性的早期影响，以及美西律和钙蛋白酶-2抑制剂对微管相关蛋白-2（MAP-2）降解的预防。将24只大鼠分为4组：对照组（1）;创伤组（2）;美西来汀预处理创伤组（3）;创伤后给予钙蛋白酶-2抑制剂组（4）。所有动物均受到轻度、闭合性头部创伤。额叶被删除和处理的MAP-2细胞骨架蛋白的染色和免疫荧光标记，这是通过共聚焦显微镜在连续的光学切片显示受影响的地区的三维细胞结构进行评估。MAP-2装饰在几乎所有的神经元从创伤的大脑区域急剧减少，而微小的丝状和颗粒状的轮廓轴突和/或树突保留在一起，这意味着大量的降解/解聚的微管。相比之下，在mexiletine预处理的动物中，轴突和核周轮廓中的MAP-2阳性相当保留，这清楚地描绘了mexiletine在创伤后的保护作用。与美西来汀预处理组相比，calpain-2抑制剂处理组显示MAP-2表达较不完好。美西律可防止轻度脑外伤后细胞骨架结构和蛋白质降解。钙蛋白酶-2抑制剂防止蛋白质降解，但细胞骨架组织更好地保存与美西律。
The objective of the study was to address the early effects of mild, closed, head injuries on neuronal stability and the prevention of microtubule-associated protein-2 (MAP-2) degradation by mexiletine and calpain-2 inhibitor. Twenty-four rats were divided into four groups: control group (1); trauma group without treatment (2); mexiletine-pretreated and subjected to trauma group (3); trauma subjected and then calpain-2 inhibitor received group (4). All animals were subjected to mild, closed, head trauma. Frontal lobes were removed and processed for staining and immunofluorescent labelling of MAP-2 cytoskeletal proteins, which were evaluated by confocal microscopy in serial optical sections showing the three dimensional cytoarchitecture of affected areas. MAP-2 decoration in almost all neurons obtained from traumatized brain regions drastically diminished, while minute filamentous and granular profiles in axons and/or dendrites were retained together implying a massive degradation/depolymerization of microtubules. In contrast, in mexiletine-pretreated animals, MAP-2 positivity in axonal and perikaryonal profiles was fairly retained, which clearly depicts the protective role of mexiletine after trauma. Compared with mexiletine-pretreated group, calpain-2 inhibitor treated group displayed a less well-preserved MAP-2 expression. Mexiletine can prevent cytoskeletal structure and protein degradation after mild head trauma. Calpain-2 inhibitor prevents protein degradation, but cytoskeletal organization is better preserved with mexiletine.