Neuropathological and therapeutic studies on adult motoneuron degeneration using rat peripheral nerve avulsion models

我们利用成年大鼠周围神经撕脱伤模型来评价神经保护分子对运动神经元退行性变的影响。撕取成年Fischer 344雄性大鼠右侧面神经，将编码胶质细胞系源性神经营养因子（GDNF）、脑源性神经营养因子（BDNF）、转化生长因子-β2 （tgf -β2）和生长抑制因子（GIF）的腺病毒载体注入面神经管。载体处理可显著防止受损面部运动神经元的丢失，提高胆碱乙酰转移酶（ChAT）的免疫反应性，抑制这些神经元中一氧化氮合酶活性的诱导。在单独的实验中，动物在撕脱后口服神经保护化合物T-588溶液。T-588均能改善损伤运动神经元的存活，改善其ChAT免疫反应性。上述结果提示，GDNF、BDNF、TGFβ2和GIF基因转移和口服T-588可预防运动神经元损伤和运动神经元疾病的成人运动神经元变性。

We have utilized adult rat peripheral nerve avulsion models to evaluate the effects of neuroprotective molecules on motoneuron degeneration. The right facial nerves of adult Fischer 344 male rats were avulsed and adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), transforming growth factor-β2 (TGFβ2), and growth inhibitory factor (GIF) were injected into the facial canal. The treatment with the vectors significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase (ChAT) immunoreactivity and suppressed the induction of nitric oxide synthase activity in these neurons. In separate experiments, animals were orally administered solution of a neuroprotective compound T-588 after avulsion. Both free oral administration and oral tube administration of T-588 improved the survival of injured motoneurons and ameliorated their ChAT immunoreactivity. These results indicate that the gene transfer of GDNF, BDNF, TGFβ2, and GIF and oral administration of T-588 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.