Training of the impaired forelimb after traumatic brain injury enhances hippocampal neurogenesis in the Emx1 null mice lacking a corpus callosum.
Training of the impaired forelimb after traumatic brain injury enhances hippocampal neurogenesis in the Emx1 null mice lacking a corpus callosum.
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DOI：
10.1016/j.bbr.2016.09.013
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发表时间：
2018-03-15
影响因子：
2.7
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Neumann M;Liu W;Sun C;Yang SY;Noble-Haeusslein LJ;Liu J
众所周知，单侧脑损伤会破坏两个皮质之间的平衡，从运动皮质M1完好到M1损伤的异常高的大脑半球间抑制驱动经颧骨传递就是明证。我们以前的工作表明，同源异型盒基因Emx1的缺失不仅导致了胼胝体发育不全，而且还导致了海马神经发生的减少。目前的研究试图确定缺乏cc是否影响单侧创伤性脑损伤小鼠患肢训练后前肢功能和海马可塑性的恢复。脑挫伤后1周，采用皮质冲击法损伤小鼠的偏爱肢体，对Emx1野生型(WT)和基因敲除(KO)小鼠进行4周的单颗粒到达患肢的任务。TBI和Emx1缺失对REACH成功率有总体不利影响。然而，TBI只对WT小鼠的REACH表现有显著影响，而对KO小鼠没有影响。TBI和Emx1基因缺失也对海马神经发生产生负面影响，表现为双皮质素(DCX)表达的未成熟神经元减少，而肢体训练增强了DCX的表达。然而，肢体训练仅在脑外伤治疗组增加了KO小鼠的DCX细胞，而无论治疗方法如何，它在两个WT组小鼠中都诱导了神经发生。我们的发现还表明，肢体训练增强了脑损伤后包括海马体在内的功能偏远区域的神经可塑性，这可能对促进脑创伤后功能的整体恢复有一定意义。
Unilateral brain injury is known to disrupt the balance between the two cortices, as evidenced by an abnormally high interhemispheric inhibitory drive from motor cortex M1intact to M1lesioned transmitted transcallosally. Our previous work has shown that the deletion of homeobox gene Emx1 not only led to the agenesis of the corpus callosum (cc), but also to reduced hippocampal neurogenesis. The current study sought to determine whether lacking the cc affected the recovery of forelimb function and hippocampal plasticity following training of the affected limb in mice with unilateral traumatic brain injuries (TBI). One week after TBI, produced by a controlled cortical impact to impair the preferred limb, Emx1 wild type (WT) and knock out (KO) mice were subjected to the single-pellet reaching task with the affected limb for 4 weeks. Both TBI and Emx1 deletion had overall adverse effects on the successful rate of reaching. However, TBI significantly affected reaching performance only in the WT mice and not in the KO mice. Both TBI and Emx1 gene deletion also negatively affected hippocampal neurogenesis, demonstrated by a reduction in doublecortin (DCX)-expressing immature neurons, while limb training enhanced DCX expression. However, limb training increased DCX cells in KO mice only in the TBI-treated group, whereas it induced neurogenesis in both WT mice groups regardless of the treatment. Our finding also suggests that limb training enhances neuroplasticity after brain injury at functionally remote regions including the hippocampus, which may have implications for promoting overall recovery of function after TBI.