Neurochirurgisches Forschungslabor, Universität des Saarlandes, Homburg/Saar, Germany.
J Mol Neurosci. 2012 Feb;46(2):401-9. doi: 10.1007/s12031-011-9600-9. Epub 2011 Aug 11.
The importance of stem cells to ameliorate the devastating consequences of traumatic injuries in the adult mammalian central nervous system calls for improvements in the capacity of these cells to cope, in particular, with the host response to the injury. We have previously shown, however, that in the acutely traumatized spinal cord local energy metabolism led to decreased ATP levels after neural stem cell (NSC) transplantation. As this might counteract NSC-mediated regenerative processes, we investigated if NSC selected for increased oxidative stress resistance are better suited to preserve local energy content. For this purpose, we exposed wild-type (WT) NSC to hydrogen peroxide prior to transplantation. We demonstrate here that transplantation of WT-NSC into a complete spinal cord compression injury model even lowers the ATP content beyond the level detected in spinal cord injury-control animals. Compared to WT-NSC, stress-resistant (SR) NSC did not lead to a further decrease in ATP content. These differences between WT- and SR-NSC were observed 4 h after the lesion with subsequent transplantation. At 24 h after lesioning, these differences were no more as obvious. Thus, in contrast to native NSC, transplantation of NSC selected for oxidative stress resistance can positively influence local energy metabolism in the first hours after spinal cord compression. The functional relevance of this observation has to be tested in further experiments.
干细胞对于改善成年哺乳动物中枢神经系统创伤性损伤的破坏性后果非常重要，这就需要提高这些细胞的适应能力，特别是适应宿主对损伤的反应。然而，我们之前已经表明，在急性创伤性脊髓损伤后，神经干细胞（NSC）移植后局部能量代谢导致 ATP 水平降低。由于这可能会抵消 NSC 介导的再生过程，我们研究了是否选择具有更高抗氧化应激能力的 NSC 更适合维持局部能量含量。为此，我们在移植前将野生型（WT）NSC 暴露于过氧化氢中。我们在这里证明，将 WT-NSC 移植到完全脊髓压迫损伤模型中，甚至会使 ATP 含量进一步降低到脊髓损伤对照动物检测到的水平以下。与 WT-NSC 相比，应激耐受（SR）NSC 不会导致 ATP 含量进一步降低。这些 WT-和 SR-NSC 之间的差异在损伤后 4 小时即可观察到，并在随后的移植中观察到。在损伤后 24 小时，这些差异不再明显。因此，与天然 NSC 相比，移植选择具有抗氧化应激能力的 NSC 可以在脊髓压迫后的最初几个小时内积极影响局部能量代谢。这一观察结果的功能相关性需要在进一步的实验中进行测试。
