Depression and anxiety have been reported as the major neuropsychiatric consequences following stroke. Minocycline, a neuroprotective drug has minimized depressive symptoms in patients with major depressive disorders and anxiety-like symptoms. In addition, minocycline demonstrated efficacy and seemed a promising neuroprotective agent in acute stroke patients. The present studied evaluated the effects of minocycline treatment on the depression and anxiety-like behaviors, brain damage and expression of inflammatory and neuroprotective mediators after transient global cerebral ischemia in C57BL/6 mice. Brain ischemia was induced by bilateral occlusion of the common carotids (BCCAo) for 25 min and subsequent reperfusion. Sham and BCCAo animals received minocycline at a dose of 30 mg/kg by intraperitoneal injection during 14 days. The locomotor activity, depression and anxiety-like behaviors were assessed by open field, forced swim and elevated plus maze tests, respectively. Then, the brains were removed and processed to evaluate brain damage by histological and morphometric analysis, hippocampal neurodegeneration using Fluoro-Jade C histochemistry, microglial activity using iba-1 immunohistochemistry, brain levels of TNF, IFN-γ, IL-6, IL-10, IL-12p70 and CCL2 by CBA, CX3CL1 and BDNF by ELISA assays. The animals developed depression and anxiety-like behaviors post-stroke and minocycline treatment prevented those neurobehavioral changes. Moreover, minocycline-treated BCCAo animals showed less intense brain damage in the cerebral cortex, brainstem and cerebellum as well as significantly reduced hippocampal neurodegeneration. BCCAo groups exhibited up-regulation of some cytokines at day 14 after ischemia and brain levels of CX3CL1 and BDNF remained unaltered. Our data indicate that the depression and anxiety-like behavioral improvements promoted by minocycline treatment might be related to its neuroprotective effect after brain ischemia in mice.

中文翻译：

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米诺环素治疗可预防实验性缺血性中风后的抑郁和焦虑样行为，并促进神经保护作用。

据报道，抑郁和焦虑是中风后主要的神经精神病学后果。Minocycline是一种神经保护药物，可将患有严重抑郁症和焦虑症的患者的抑郁症状降至最低。此外，米诺环素在急性中风患者中显示出疗效，并且似乎是一种有前途的神经保护剂。本研究评估了米诺环素治疗对短暂性全脑缺血后C57BL / 6小鼠抑郁和焦虑样行为，脑损伤以及炎性和神经保护性介质表达的影响。脑缺血是由双侧颈总动脉（BCCAo）闭塞25分钟和随后的再灌注引起的。假手术和BCCAo动物在14天内通过腹膜内注射以30 mg / kg的剂量服用米诺环素。运动能力，抑郁和焦虑样行为分别通过开阔地域，强迫游泳和高架迷宫测试进行评估。然后，取出大脑并进行处理，以通过组织学和形态计量学分析，使用Fluoro-Jade C组织化学方法检测海马神经变性，使用iba-1免疫组织化学方法检测小胶质细胞活性，大脑中的TNF，IFN-γ，IL-6，IL- 10，IL-12p70和CCL2通过CBA，CX3CL1和BDNF通过ELISA测定。这些动物在中风后出现抑郁和焦虑样行为，而米诺环素治疗阻止了这些神经行为的改变。此外，用米诺环素治疗的BCCAo动物在大脑皮层，脑干和小脑中的脑部损伤较小，并且海马神经变性明显减少。缺血后第14天，BCCAo组表现出一些细胞因子的上调，并且CX3CL1和BDNF的脑水平保持不变。我们的数据表明，米诺环素治疗促进的抑郁和焦虑样行为改善可能与其对小鼠脑缺血后的神经保护作用有关。