Investigation of nerve plasticity for the better results of nerve repair

臂丛（BP）脊神经根的撕脱可以通过神经移植物交叉神经转移修复，将损伤的神经末梢连接到受损侧的BP。这些患者的感觉恢复表明，对侧初级体感觉皮层（S1）被绕过对侧BP的传入输入激活。为了证实这一假设，本研究通过使用经颅黄蛋白荧光成像来观察小鼠穿越神经转移后的皮层活动。在幼年小鼠中，施加于前爪的振动刺激在受刺激侧的S1中引起了局部荧光反应，而在同侧S1中几乎没有活性。交叉神经移植4周后，前爪刺激损伤和修复侧仅在受刺激侧同侧S1区产生皮质反应。在交叉神经移植后8周，前爪刺激导致两脑半球的S1或更多的反应。这些皮层反应通过切断用于修复的神经移植物而被消除。将同侧S1暴露在蓝色激光下可以抑制同侧S1以及对侧S1的皮质反应，这表明同侧反应通过皮质-皮质通路传播到对侧S1。直接高频刺激同侧S1结合前爪刺激急性诱导小鼠前爪区S1双侧皮质表征。在皮质限制性异型GluN1（NMDAR1）敲除小鼠中，交叉神经转移后对侧S1的皮质反应降低。在两个半球S1之间皮质-皮质通路受损的基因操纵小鼠中，没有清楚地观察到功能的双侧皮质表征。综上所述，这些发现强烈表明，皮质-皮质通路的活动依赖性增强对神经转移后患者的感觉恢复起着关键作用

Avulsion of spinal nerve roots in the brachial plexus(BP) can be repaired by crossing nerve transfer via a nerve graft to connect injured nerve ends to the BP contralateral to the lesioned side. Sensory recovery in these patients suggests that the contralateral primary somatosensory cortex(S1) is activated by afferent inputs that bypassed to the contralateral BP. To confirm this hypothesis, the present study visualized cortical activity after crossing nerve transfer in mice through the use of transcranial flavoprotein fluorescence imaging. In naive mice, vibratory stimuli applied to the forepaw elicited localized fluorescence responses in the S1 contralateral to the stimulated side, with almost no activity in the ipsilateral S1. Four weeks after crossing nerve transfer, forepaw stimulation in the injured and repaired side resulted in cortical responses only in the S1 ipsilateral to the stimulated side. At eight weeks after crossing nerve transfer, forepaw stimulation resulted in S1 cor … More tical responses of both hemispheres. These cortical responses were abolished by cutting the nerve graft used for repair. Exposure of the ipsilateral S1 to blue laser light suppressed cortical responses in the ipsilateral S1, as well as in the contralateral S1, suggesting that ipsilateral responses propagated to the contralateral S1 via cortico-cortical pathways. Direct high-frequency stimulation of the ipsilateral S1 in combination with forepaw stimulation acutely induced S1 bilateral cortical representation of the forepaw area in naive mice. Cortical responses in the contralateral S1 after crossing nerve transfer were reduced in cortex-restricted heterotypic GluN1(NMDAR1) knockout mice. Functional bilateral cortical representation was not clearly observed in genetically manipulated mice with impaired cortico-cortical pathways between S1 of both hemispheres. Taken together, these findings strongly suggest that activity-dependent potentiation of cortico-cortical pathways has a critical role for sensory recovery in patients after crossing nerve transfer Less