Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-970 Campinas, SP, Brazil.
Neuroscience. 2013 Oct 10;250:715-32. doi: 10.1016/j.neuroscience.2013.07.043. Epub 2013 Jul 27.
Compression of spinal roots is an important medical problem, which may arise from intervertebral disc herniation, tumor growth or as a result of high energy accidents. Differently from avulsion, root crushing maintains the central/peripheral nervous system (CNS/PNS) connection, although the axons are axotomized and motoneurons degenerate. Such neuronal death may decrease and delay motor function recovery. In the present study we have investigated the neuroprotective effects of mesenchymal stem cell (MSC) therapy following such proximal lesions. Motor recovery and synaptic stabilization were analyzed by the use of morphological and functional approaches. For that, crushing the ventral roots at L4, L5 and L6 was unilaterally performed in Lewis rats. Four weeks after injury, an increased motoneuron survival was observed in the MSC-treated group, coupled with a smaller decrease of inputs at the motoneuron surface and nearby neuropil, seen by synaptophysin and synapsin immunolabeling and decreased astrogliosis, seen by GFAP immunolabeling. In this sense, MSC-treated group displayed a significant preservation of GABAergic terminals, indicating a possible neuroprotection to glutamate excitotoxicity. Motor function recovery was acutely improved in MSC-treated group as compared to Dulbeco's modified eagle medium (DMEM)-treated. Overall, we provide evidence that ventral root crushing (VRC), although milder than avulsion, results in significant loss of motoneurons (~51%) that can be reduced by MSC administration within the spinal cord. Such treatment also improves the number of synapses immunoreactive against molecules present in inhibitory inputs. Also, an increased number of regenerated axons was obtained in the MSC-treated group, in comparison to the DMEM-treated control. Overall, MSC therapy acutely improved limb strength and gait coordination, indicating a possible clinical application of such treatment following proximal lesions at the CNS/PNS interface.
脊神经根受压是一个重要的医学问题，可能由椎间盘突出、肿瘤生长或高能事故引起。与神经根撕脱不同，根挤压虽然轴突被切断，运动神经元退化，但仍保持中枢/周围神经系统（CNS/PNS）的连接。这种神经元死亡可能会减少并延迟运动功能的恢复。在本研究中，我们研究了间质干细胞（MSC）治疗对这种近端损伤的神经保护作用。通过形态学和功能方法分析运动功能的恢复和突触稳定。为此，在 Lewis 大鼠的 L4、L5 和 L6 侧根进行单侧挤压。损伤后 4 周，在 MSC 治疗组中观察到运动神经元存活率增加，同时运动神经元表面和附近神经毡的输入减少，突触小体和突触素免疫标记减少，星形胶质细胞增生减少，GFAP 免疫标记减少。在这种意义上，MSC 治疗组显示 GABA 能末梢明显保存，表明对谷氨酸兴奋性毒性有潜在的神经保护作用。与 Dulbeco 改良鹰培养基（DMEM）治疗组相比，MSC 治疗组的运动功能恢复明显改善。总之，我们提供的证据表明，尽管侧根挤压（VRC）比神经根撕脱轻微，但仍会导致大量运动神经元（~51%）丢失，而 MSC 给药可减少这种丢失。这种治疗方法还改善了对抑制性输入中存在的分子有免疫反应的突触数量。此外，与 DMEM 治疗对照组相比，MSC 治疗组获得了更多再生轴突。总之，MSC 治疗急性改善了肢体力量和步态协调，表明这种治疗方法在 CNS/PNS 界面的近端损伤后具有潜在的临床应用。
