Minocycline effects on cerebral edema: Relations with inflammatory and oxidative stress markers following traumatic brain injury in mice
Minocycline effects on cerebral edema: Relations with inflammatory and oxidative stress markers following traumatic brain injury in mice
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DOI：
10.1016/j.brainres.2009.07.031
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发表时间：
2009-09-21
期刊：
影响因子：
2.9
通讯作者：
Jafarian-Tehrani, Mehrnaz
中科院分区：
文献类型：
--
作者：
Homsi, Shadi;Federico, Fabiola;Jafarian-Tehrani, Mehrnaz
脑水肿是脑外伤（TBI）后的严重并发症之一，其有效治疗对于防止进一步的脑损伤具有重要意义。本研究通过比较不同的剂量方案，研究了以抗炎特性而闻名的米诺环素对脑水肿及其各自的炎症标志物、氧化应激和TBI后神经功能障碍的影响。使用体重下降模型来诱导小鼠中的TBI。测量脑含水量以评估脑水肿。采用酶联免疫吸附试验（ELISA）、酶谱法和蛋白印迹法（Western blot）检测炎症标志物（IL-1 β）。采用Griffith技术检测氧化应激指标（谷胱甘肽水平），采用绳试验检测神经功能。在TBI后腹膜内给予米诺环素一次（5分钟）、两次（5分钟和3小时）或三次（5分钟、3小时和9小时）。米诺环素的第一剂量仅变化（45或90 mg/kg），而随后的剂量均为45 mg/kg。二甲胺四环素的单次和两次给药减少了TBI后6 h炎性标志物的增加。米诺环素也减少脑水肿在这个时间点，只有在双重管理和高剂量方案，虽然没有影响TBI诱导的氧化型谷胱甘肽增加。米诺环素的抗水肿作用持续长达24小时，三次给药后，并伴随着神经恢复。总之，我们报告了二甲胺四环素的抗水肿作用后，TBI小鼠根据一个特定的治疗方案。这些发现强调了米诺环素的有益作用取决于脑损伤后的治疗方案。(C)2009 Elsevier B. V.保留所有权利。
One of the severe complications following traumatic brain injury (TBI) is cerebral edema and its effective treatment is of great interest to prevent further brain damage. This study investigated the effects of minocycline, known for its anti-inflammatory properties, on cerebral edema and its respective inflammatory markers by comparing different dose regimens, on oxidative stress and on neurological dysfunction following TBI. The weight drop model was used to induce TBI in mice. The brain water content was measured to evaluate cerebral edema. Inflammatory markers were detected by ELISA (IL-1 beta), zymography and Western blot (MMP-9). The oxidative stress marker (glutathione levels) and neurological function were measured by Griffith technique and string test, respectively. Minocycline was administered i.p. once (5 min), twice (5 min and 3 h) or triple (5 min, 3 h and 9 h) following TBI. The first dose of minocycline only varied (45 or 90 mg/kg), whereas the following doses were all at 45 mg/kg. The single and double administrations of minocycline reduced the increase of inflammatory markers at 6 h post-TBI. Minocycline also reduced cerebral edema at this time point, only after double administration and at the high dose regimen, although with no effect on the TBI-induced oxidized glutathione increase. The anti-edematous effect of minocycline persisted up to 24 h, upon a triple administration, and accompanied by a neurological recovery. In conclusion, we reported an anti-edematous effect of minocycline after TBI in mice according to a specific treatment regimen. These findings emphasize that the beneficial effects of minocycline depend on the treatment regimen following a brain injury. (C) 2009 Elsevier B.V. All rights reserved.