Rapamycin protects neurons from brain contusion‑induced inflammatory reaction via modulation of microglial activation.
Rapamycin protects neurons from brain contusion‑induced inflammatory reaction via modulation of microglial activation.
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DOI：
10.3892/mmr.2015.4407
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发表时间：
2015-11
影响因子：
3.4
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Song Q;Xie D;Pan S;Xu W
炎症反应在颅脑损伤后继发性损伤中起重要作用。雷帕霉素已经被证明是一种神经保护剂，在小鼠脑损伤模型中，然而，关于雷帕霉素对脑损伤后炎症反应的影响的数据缺乏。因此，本研究旨在评估雷帕霉素治疗对炎症反应的影响，并研究脑外伤后小胶质细胞激活的可能参与。雄性印迹控制区小鼠随机分为4组：假手术组(n=23)、脑损伤组(n=23)、脑损伤+二甲基亚砜(DMSO)组(n=31)和脑损伤+雷帕霉素组(n=31)。将雷帕霉素溶于DMSO(50 mg/ml)，伤后30min腹腔注射雷帕霉素(2 mg/kg)。建立大鼠颅脑损伤后体重下降模型，伤后24 h取脑组织。结果表明，颅脑损伤后应用雷帕霉素与损伤周围部位活化的小胶质细胞和神经元变性水平降低、促炎细胞因子水平降低和神经行为功能增强有关，可能与雷帕霉素途径的哺乳动物靶点失活有关。本研究的结果为雷帕霉素抗神经炎作用的机制提供了新的见解，可能涉及调节小胶质细胞的激活。
The inflammatory reaction is important in secondary injury following traumatic brain injury (TBI). Rapamycin has been demonstrated as a neuroprotective agent in a mouse model of TBI, however, there is a lack of data regarding the effects of rapamycin on the inflammatory reaction following TBI. Therefore, the present study was designed to assess the effects of treatment with rapamycin on inflammatory reactions and examine the possible involvement of microglial activation following TBI. Male imprinting control region mice were randomly divided into four groups: Sham group (n=23), TBI group (n=23), TBI + dimethyl sulfoxide (DMSO) group (n=31) and TBI + rapamycin group (n=31). Rapamycin was dissolved in DMSO (50 mg/ml) and injected 30 min after TBI (2 mg/Kg; intraperitoneally). A weight-drop model of TBI was induced, and the brain tissues were harvested 24 h after TBI. The findings indicated that the administration of rapamycin following TBI was associated with decreased levels of activated microglia and neuron degeneration at the peri-injury site, reduced levels of proinflammatory cytokines and increased neurobehavioral function, possibly mediated by inactivation of the mammalian target of rapamycin pathway. The results of the present study offer novel insight into the mechanisms responsible for the anti-neuroinflammatory effects of rapamycin, possibly involving the modulation of microglial activation.