Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
J Neurosci Res. 2019 Apr;97(4):520-534. doi: 10.1002/jnr.24365. Epub 2018 Dec 14.
Astrogliosis and microglial reactions are correlated with the formation of scar tissue and synapse loss. 4-hydroxy-tempo (TEMPOL) is a reactive oxygen species scavenger with proven neuroprotective efficacy in experimental models of traumatic injury and cerebral ischemia. TEMPOL has not, however, been applied following ventral root lesions, which are particularly correlated with the degeneration of spinal motoneurons following brachial plexus injuries. Thus, the present study investigated the effects of TEMPOL on motoneurons and adjacent glial reactions, with a particular focus on the preservation of excitatory and inhibitory spinal circuits. Adult female Sprague Dawley rats were subjected to ventral root crush (VRC) at the lumbar intumescence. Animals were divided into the following experimental groups: (a) VRC-saline treatment; (b) VRC-TEMPOL treatment (12 mg/kg, n = 5), and (c) VRC-TEMPOL treatment (250 mg/kg, n = 5). The spinal cord tissue located contralateral to the lesion was used as the control. Fourteen days after lesioning, the rats were euthanized and the spinal cords were removed for motoneuron counting and immunolabeling with glial (GFAP and Iba-1) and synapse markers (synaptophysin, VGLUT-1, and GAD65). Although TEMPOL did not exert neuroprotective effects at the studied concentrations, the modulation of glial reactions was significant at higher doses. Thus, synaptophysin staining was preserved and, in particular, VGLUT-1-positive inputs were maintained, thereby indicating that TEMPOL preserved proprioceptive glutamatergic inputs without exacerbating the rate of motoneuron degeneration. Consequently, its administration with other efficient neuroprotective substances may significantly improve the outcomes following spinal cord lesioning.
星形胶质细胞和小胶质细胞反应与疤痕组织的形成和突触丧失有关。4-羟基-TEMPOL（TEMPOL）是一种活性氧物质清除剂，在创伤性损伤和脑缺血的实验模型中已被证明具有神经保护作用。然而，TEMPOL 尚未应用于腹根损伤后，腹根损伤与臂丛损伤后脊髓运动神经元的退化特别相关。因此，本研究调查了 TEMPOL 对运动神经元和相邻神经胶质反应的影响，特别关注兴奋性和抑制性脊髓回路的保留。成年雌性 Sprague Dawley 大鼠在腰椎膨隆处进行腹根挤压（VRC）。动物分为以下实验组：（a）VRC-生理盐水处理；（b）VRC-TEMPOL 处理（12mg/kg，n=5），和（c）VRC-TEMPOL 处理（250mg/kg，n=5）。病变对侧的脊髓组织用作对照。损伤后 14 天，处死大鼠，取出脊髓进行运动神经元计数和神经胶质（GFAP 和 Iba-1）和突触标记物（突触素、VGLUT-1 和 GAD65）免疫标记。尽管 TEMPOL 在研究浓度下没有发挥神经保护作用，但在较高剂量下对神经胶质反应的调节是显著的。因此，突触素染色得到保留，特别是 VGLUT-1 阳性输入得到维持，这表明 TEMPOL 保留了本体感受谷氨酸能输入，而不会加剧运动神经元退化的速度。因此，其与其他有效神经保护物质联合使用可能会显著改善脊髓损伤后的结果。
