Homsi Shadi, Federico Fabiola, Croci Nicole, Palmier Bruno, Plotkine Michel, Marchand-Leroux Catherine, Jafarian-Tehrani Mehrnaz
Laboratoire de Pharmacologie de la Circulation Cérébrale (EA 2510), Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75006 Paris, France.
Brain Res. 2009 Sep 29;1291:122-32. doi: 10.1016/j.brainres.2009.07.031. Epub 2009 Jul 23.
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-1beta), 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.
创伤性脑损伤（TBI）后的严重并发症之一是脑水肿，其有效治疗对于预防进一步的脑损伤至关重要。本研究通过比较不同剂量方案，研究了以其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。采用重物坠落模型诱导小鼠TBI。测量脑含水量以评估脑水肿。通过ELISA（IL-1β）、酶谱分析和蛋白质免疫印迹法（MMP-9）检测炎症标志物。分别通过格里菲斯技术和细绳试验测量氧化应激标志物（谷胱甘肽水平）和神经功能。在TBI后腹腔注射一次（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。米诺环素的第一剂仅有所不同（45或90mg/kg），而后续剂量均为45mg/kg。米诺环素单次和两次给药可降低TBI后6小时炎症标志物的增加。米诺环素在这个时间点也能减轻脑水肿，仅在两次给药且高剂量方案时有效，尽管对TBI诱导的氧化型谷胱甘肽增加没有影响。米诺环素的抗水肿作用在三次给药后可持续24小时，并伴有神经功能恢复。总之，我们报道了根据特定治疗方案，米诺环素在小鼠TBI后具有抗水肿作用。这些发现强调米诺环素的有益作用取决于脑损伤后的治疗方案。
