Department of Emergency Medicine, Emory University, Atlanta, GA, USA.
Restor Neurol Neurosci. 2011;29(4):215-25. doi: 10.3233/RNN-2011-0593.
Recent work indicates that transplanted neural stem cells (NSCs) can survive, migrate to the injury site, and facilitate recovery from traumatic brain injury (TBI). The present study manipulated timing and location of NSC transplants following controlled cortical impact injury (CCI) in mice to determine optimal transplant conditions.
In Experiment 1 (timing), NSCs (E14.5 mouse) were injected into the host striatum, ipsilateral to the injury, at 2, 7, or 14 days. In Experiment 2 (location), NSCs or vehicle were injected into the mouse striatum (7 days post-CCI) either ipsilateral or contralateral to the injury and cognitive and motor abilities were assessed from weeks 1-8 post-transplant. Histological measures of NSC survival, migration, and differentiation were taken at 6 and 8 weeks post-transplant.
The results demonstrate that: (1) 2-7 days post-injury is the optimal time-range for delivering NSCs; (2) time of transplantation does not affect short-term phenotypic differentiation; (3) transplant location affects survival, migration, phenotype, and functional efficacy; and (4) NSC-mediated functional recovery is not contingent upon NSC migration or phenotypic differentiation.
These findings provide further support for the idea that mechanisms other than the replacement of damaged neurons or glia, such as NSC-induced increases in protective neurotrophic factors, may be responsible for the functional recovery observed in this model of TBI.
最近的研究表明，移植的神经干细胞（NSCs）可以存活、迁移到损伤部位，并促进创伤性脑损伤（TBI）的恢复。本研究通过对小鼠控制性皮质撞击伤（CCI）后进行 NSC 移植的时机和部位的操作，以确定最佳的移植条件。
在实验 1（时机）中，将 E14.5 期小鼠的 NSCs 注射到宿主纹状体，即损伤侧的同侧。在实验 2（部位）中，将 NSCs 或载体在 CCI 后 7 天注射到同侧或对侧的小鼠纹状体，并在移植后 1-8 周评估认知和运动能力。在移植后 6 和 8 周时，进行 NSC 存活、迁移和分化的组织学测量。
结果表明：（1）损伤后 2-7 天是递送 NSCs 的最佳时间范围；（2）移植时间不影响短期表型分化；（3）移植部位影响存活、迁移、表型和功能效果；（4）NSC 介导的功能恢复不一定依赖于 NSC 迁移或表型分化。
这些发现进一步支持了这样的观点，即除了替代受损神经元或神经胶质细胞之外，例如 NSC 诱导的保护性神经营养因子增加等机制，可能是导致 TBI 模型中观察到的功能恢复的原因。
