Scorisa Juliana Milani, Zanon Renata Graciele, Freria Camila Marques, de Oliveira Alexandre Leite Rodrigues
Dept. of Anatomy - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Neurosci Lett. 2009 Feb 13;451(1):34-9. doi: 10.1016/j.neulet.2008.12.017. Epub 2008 Dec 16.
Avulsion of ventral roots induces degeneration of most axotomized motoneurons. At present there are no effective strategies to prevent such neuronal loss and to preserve the affected spinal circuits. Interestingly, changes in the spinal cord network also occur during the course of the experimental model of multiple sclerosis (experimental autoimmune encephalomyelitis-EAE). Glatiramer acetate (GA) significantly reduces the seriousness of the symptoms during the exacerbation of EAE. However, little is known about its effects on motoneurons. In the present study, we investigated whether GA has an influence on synapse plasticity and glial reaction after ventral root avulsion (VRA). Lewis rats were subjected to the avulsion of lumbar ventral roots and treated with GA. The animals were sacrificed after 14 days of treatment and the spinal cords processed for immunohistochemistry. A correlation between the synaptic changes and glial activation was obtained by performing immunolabeling against synaptophysin, GFAP and Iba-1. GA treatment preserved synaptophysin labeling, and significantly reduced the glial reaction in the area surrounding the axotomized motoneurons. After ventral root avulsion, GA treatment was also neuroprotective. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which may in turn contribute to future treatment strategies after proximal lesions to spinal motoneurons.
腹侧神经根撕脱会导致大多数轴突切断的运动神经元发生退变。目前尚无有效的策略来预防此类神经元丢失并保留受影响的脊髓回路。有趣的是，在多发性硬化症实验模型（实验性自身免疫性脑脊髓炎-EAE）过程中，脊髓网络也会发生变化。醋酸格拉替雷（GA）在EAE病情加重期间可显著减轻症状的严重程度。然而，其对运动神经元的影响却知之甚少。在本研究中，我们调查了GA对腹侧神经根撕脱（VRA）后突触可塑性和胶质细胞反应是否有影响。对Lewis大鼠进行腰段腹侧神经根撕脱并给予GA治疗。治疗14天后处死动物，对脊髓进行免疫组织化学处理。通过对突触素、胶质纤维酸性蛋白（GFAP）和离子钙结合衔接分子1（Iba-1）进行免疫标记，获得突触变化与胶质细胞激活之间的相关性。GA治疗可保留突触素标记，并显著减轻轴突切断的运动神经元周围区域的胶质细胞反应。腹侧神经根撕脱后，GA治疗也具有神经保护作用。目前的结果表明，免疫调节剂GA对脊髓神经末梢的稳定性有影响，这反过来可能有助于制定脊髓运动神经元近端损伤后的未来治疗策略。
