Department of Neurosurgery, Tangshan Gongren Hospital, No. 27 Wen Hua Road, Tangshan, 063000, People's Republic of China,
Neurol Sci. 2014 May;35(5):677-82. doi: 10.1007/s10072-013-1575-6. Epub 2013 Nov 13.
Traumatic brain injury (TBI) can initiate a series of complicated pathological events, and induce various types of neuronal cell death including autophagy and apoptosis. Currently, the treatment of TBI is one of the main challenges in neurobiology. In this regard, the administration of bone marrow stromal cells (BMSCs) represents a novel treatment modality for TBI. However, the protective mechanism of BMSCs was unknown in the TBI. The aim of the present study was to assess the effects of BMSCs on connexin 43(CX43) and autophagy in the hippocampus following TBI in rats. A rat model of TBI was created using a modified weight-drop device. Double-membrane structures in the process of autophagy formation were frequently observed in injured brain by electron microscopy. The levels of autophagic pathway associated proteins and CX43 were also detected by western blot analysis. Specifically, immunoblotting results showed that BMSCs treatment after TBI could down-regulate light chain 3 (LC3), Beclin-1 and CX43 expression in the hippocampus. Taken together, our results demonstrated that BMSCs were able to significantly suppress TBI-induced autophagy activity, and the potential mechanism by regulating CX43 levels.
创伤性脑损伤 (TBI) 可引发一系列复杂的病理事件,并诱导多种类型的神经元细胞死亡,包括自噬和细胞凋亡。目前,TBI 的治疗是神经生物学的主要挑战之一。在这方面,骨髓基质细胞 (BMSCs) 的给药代表了 TBI 的一种新的治疗方式。然而,BMSCs 在 TBI 中的保护机制尚不清楚。本研究旨在评估 BMSCs 对大鼠 TBI 后海马区连接蛋白 43(CX43)和自噬的影响。使用改良的重物坠落装置建立大鼠 TBI 模型。通过电子显微镜频繁观察到自噬形成过程中的双层膜结构。还通过 Western blot 分析检测了自噬途径相关蛋白和 CX43 的水平。具体而言,免疫印迹结果表明,TBI 后 BMSCs 治疗可下调海马区的 LC3、Beclin-1 和 CX43 表达。总之,我们的结果表明,BMSCs 能够显著抑制 TBI 诱导的自噬活性,其潜在机制可能与调节 CX43 水平有关。