Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, Sevilla 41012, Spain.
Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, Sevilla 41012, Spain
eNeuro. 2020 May 29;7(3). doi: 10.1523/ENEURO.0467-19.2020. Print 2020 May/Jun.
Vascular endothelial growth factor (VEGF) has been recently demonstrated to induce neuroprotective and synaptotrophic effects on lesioned neurons. Hitherto, the administration of VEGF in different animal models of lesion or disease has been conducted following a chronic protocol of administration. We questioned whether a single dose of VEGF, administered intraventricularly, could induce long-term neurotrophic effects on injured motoneurons. For this purpose, we performed in cats the axotomy of abducens motoneurons and the injection of VEGF into the fourth ventricle in the same surgical session and investigated the discharge characteristics of axotomized and treated motoneurons by single-unit extracellular recordings in the chronic alert preparation. We found that injured motoneurons treated with a single VEGF application discharged with normal characteristics, showing neuronal eye position (EP) and velocity sensitivities similar to control, thereby preventing the axotomy-induced alterations. These effects were present for a prolonged period of time (50 d) after VEGF administration. By confocal immunofluorescence we also showed that the synaptic stripping that ensues lesion was not present, rather motoneurons showed a normal synaptic coverage. Moreover, we demonstrated that VEGF did not lead to any angiogenic response pointing to a direct action of the factor on neurons. In summary, a single dose of VEFG administered just after motoneuron axotomy is able to prevent for a long time the axotomy-induced firing and synaptic alterations without any associated vascular sprouting. We consider that these data are of great relevance due to the potentiality of VEGF as a therapeutic agent in neuronal lesions and diseases.
血管内皮生长因子（VEGF）最近被证明对受损神经元具有神经保护和突触生成作用。迄今为止，在不同的病变或疾病动物模型中，VEGF 的给药都是通过慢性给药方案进行的。我们想知道，脑室内单次给予 VEGF 是否可以对损伤的运动神经元产生长期的神经营养作用。为此，我们在猫中进行了外展运动神经元的轴突切断术，并在同一手术中向第四脑室注射 VEGF，然后通过慢性清醒动物模型中的单细胞外记录技术研究了轴突切断和治疗后的运动神经元的放电特征。我们发现，单次给予 VEGF 治疗的损伤运动神经元以正常特征放电，表现出与对照相似的神经元眼位（EP）和速度敏感性，从而防止了轴突切断引起的改变。这些作用在 VEGF 给药后很长一段时间（50 天）内都存在。通过共聚焦免疫荧光，我们还发现，随后发生的突触剥离并不存在，而是运动神经元表现出正常的突触覆盖。此外，我们证明 VEGF 不会引起任何血管生成反应，这表明该因子对神经元有直接作用。总之，在运动神经元轴突切断后立即给予单次剂量的 VEGF，能够长时间防止轴突切断引起的放电和突触改变，而不会引起任何相关的血管生成。我们认为，由于 VEGF 作为神经元损伤和疾病的治疗剂具有潜在的可能性，这些数据具有重要意义。
