Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
Arch Med Sci. 2013 Feb 21;9(1):132-8. doi: 10.5114/aoms.2012.31438. Epub 2012 Oct 30.
Reestablishment of functional networks after traumatic brain injury (TBI) has been proffered as one of the goals of neural stem cell (NSC) transplantation therapeutics. Gap junctions provide essential means for direct cellular communication by transferring small molecules and ions, which may provide insights into the interplay between grafted NSCs and host cells.
Thirty-six adult male Wister rats were used in this study. The controlled cortical impact (CCI) model of brain injury has been performed. Seventy-two hours after CCI injury, animals were randomly assigned to two groups: PBS- and NSC- transplanted group. NSCs-transplanted group received delivery of the NSCs suspension to the cortex below the injury cavity in the ipsilateral hemisphere. At 1, 2, and 4 weeks post-transplantation, we investigated the expression patterns of gap junction-associated connexin 43 (Cx43) in the transplant site and the border of CCI by immunohistochemistry, Western blot and RT-PCR.
Our findings showed that Cx43 staining was significantly greater in the transplant site and the border of CCI in the NSCs-transplanted rats compared to the control rats at different time points (p < 0.01 at 1 week, p < 0.05 at 2 and 4 weeks). Significantly higher gene and protein expression of Cx43 was found in NSCs-transplanted rats compared to the control rats in the period of 4 weeks post-transplantation (p < 0.01), and remained at a higher level until 2 weeks with or without NSC transplantation.
It is proposed that gap junction-associated Cx43 might participate in NSCs' beneficial effects via gap-junctional coupling by which grafted NSCs integrate into host neural tissue following transplantation after TBI.
创伤性脑损伤（TBI）后功能网络的重建被认为是神经干细胞（NSC）移植治疗的目标之一。缝隙连接通过传递小分子和离子提供了直接细胞通讯的必要手段，这可能为移植的 NSCs 与宿主细胞之间的相互作用提供了深入的了解。
本研究使用了 36 只成年雄性 Wistar 大鼠。采用控制性皮质撞击（CCI）脑损伤模型。在 CCI 损伤后 72 小时，动物被随机分为两组：PBS-和 NSC-移植组。NSC 移植组将 NSCs 悬浮液递送到同侧半球损伤腔下的皮质。在移植后 1、2 和 4 周，我们通过免疫组织化学、Western blot 和 RT-PCR 研究了移植部位和 CCI 边界处缝隙连接相关连接蛋白 43（Cx43）的表达模式。
我们的研究结果表明，在不同时间点，NSC 移植大鼠的移植部位和 CCI 边界处的 Cx43 染色明显高于对照组（1 周时 p < 0.01，2 周和 4 周时 p < 0.05）。与对照组相比，在移植后 4 周内，NSC 移植大鼠的 Cx43 基因和蛋白表达明显更高（p < 0.01），并且在有无 NSC 移植的情况下，这种表达水平在 2 周内仍保持较高水平。
提出缝隙连接相关的 Cx43 可能通过缝隙连接偶联参与 NSCs 的有益作用，从而使移植后的 NSCs 在 TBI 后整合到宿主神经组织中。
