Acute minocycline treatment mitigates the symptoms of mild blast-induced traumatic brain injury.
Acute minocycline treatment mitigates the symptoms of mild blast-induced traumatic brain injury.
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DOI：
10.3389/fneur.2012.00111
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发表时间：
2012
影响因子：
3.4
通讯作者：
Agoston DV
中科院分区：
文献类型：
--
作者：
Kovesdi E;Kamnaksh A;Wingo D;Ahmed F;Grunberg NE;Long JB;Kasper CE;Agoston DV
轻度创伤性脑损伤（mTBI）由于其高患病率和整体复杂性，对民用和军事卫生保健系统构成了重大挑战。我们早期的工作表明，神经炎症，迟发性神经行为变化，和持久的记忆障碍的大鼠模型中的轻度冲击波诱导的TBI（mbTBI）的证据。本研究的目的是确定急性治疗是否与非甾体抗炎药米诺环素此外，我们的目的是评估治疗对血清和与焦虑和记忆相关的脑区域中选择的炎症、血管、神经元和神经胶质标志物的影响。（杏仁核、前额叶皮质、腹侧和背侧海马）。在单次暴露于轻度冲击波超压或假条件后4小时，我们用每日剂量的米诺环素（50 mg/kg）或生理盐水（载体）连续4天治疗动物。在受伤后第8天和第45天，我们测试了动物的运动，焦虑和空间记忆。受伤的动物表现出显著的记忆力受损和焦虑增加，特别是在稍后的测试时间点。相反，在旷场、高架十字迷宫和巴恩斯迷宫中，损伤和米诺环素治疗的大鼠的表现与对照（假手术）动物几乎相同。血清和大脑区域的蛋白质分析显示，在受伤和未治疗的大鼠中，所有测量的生物标志物（VEGF除外）的水平显著升高。重要的是，米诺环素治疗使大多数选定的炎症、血管、神经元和神经胶质标志物的血清和组织水平正常化。总之，急性米诺环素治疗似乎可以通过减轻mbTBI实验模型中损伤的分子病理学来预防神经行为异常的发展。
Mild traumatic brain injury (mTBI) represents a significant challenge for the civilian and military health care systems due to its high prevalence and overall complexity. Our earlier works showed evidence of neuroinflammation, a late onset of neurobehavioral changes, and lasting memory impairment in a rat model of mild blast-induced TBI (mbTBI). The aim of our present study was to determine whether acute treatment with the non-steroidal anti-inflammatory drug minocycline (Minocin®) can mitigate the neurobehavioral abnormalities associated with mbTBI, Furthermore, we aimed to assess the effects of the treatment on select inflammatory, vascular, neuronal, and glial markers in sera and in brain regions associated with anxiety and memory (amygdala, prefrontal cortex, ventral, and dorsal hippocampus) following the termination (51 days post-injury) of the experiment. Four hours after a single exposure to mild blast overpressure or sham conditions, we treated animals with a daily dose of minocycline (50 mg/kg) or physiological saline (vehicle) for four consecutive days. At 8 and 45 days post-injury, we tested animals for locomotion, anxiety, and spatial memory. Injured animals exhibited significantly impaired memory and increased anxiety especially at the later testing time point. Conversely, injured and minocycline treated rats’ performance was practically identical to control (sham) animals in the open field, elevated plus maze, and Barnes maze. Protein analyses of sera and brain regions showed significantly elevated levels of all of the measured biomarkers (except VEGF) in injured and untreated rats. Importantly, minocycline treatment normalized serum and tissue levels of the majority of the selected inflammatory, vascular, neuronal, and glial markers. In summary, acute minocycline treatment appears to prevent the development of neurobehavioral abnormalities likely through mitigating the molecular pathologies of the injury in an experimental model of mbTBI.