Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
Consejo Nacional de Ciencia y Tecnología, Mexico City 03940, Mexico.
Int J Mol Sci. 2023 Oct 18;24(20):15285. doi: 10.3390/ijms242015285.
Spinal cord injury (SCI) harms patients' health and social and economic well-being. Unfortunately, fully effective therapeutic strategies have yet to be developed to treat this disease, affecting millions worldwide. Apoptosis and autophagy are critical cell death signaling pathways after SCI that should be targeted for early therapeutic interventions to mitigate their adverse effects and promote functional recovery. Tibolone (TIB) is a selective tissue estrogen activity regulator (STEAR) with neuroprotective properties demonstrated in some experimental models. This study aimed to investigate the effect of TIB on apoptotic cell death and autophagy after SCI and verify whether TIB promotes motor function recovery. A moderate contusion SCI was produced at thoracic level 9 (T9) in male Sprague Dawley rats. Subsequently, animals received a daily dose of TIB orally and were sacrificed at 1, 3, 14 or 30 days post-injury. Tissue samples were collected for morphometric and immunofluorescence analysis to identify tissue damage and the percentage of neurons at the injury site. Autophagic (Beclin-1, LC3-I/LC3-II, p62) and apoptotic (Caspase 3) markers were also analyzed via Western blot. Finally, motor function was assessed using the BBB scale. TIB administration significantly increased the amount of preserved tissue ( < 0.05), improved the recovery of motor function ( < 0.001) and modulated the expression of autophagy markers in a time-dependent manner while consistently inhibiting apoptosis ( < 0.05). Therefore, TIB could be a therapeutic alternative for the recovery of motor function after SCI.
脊髓损伤（SCI）危害患者的健康和社会经济福祉。不幸的是，目前尚未开发出完全有效的治疗策略来治疗这种疾病，全球有数百万患者受到影响。凋亡和自噬是 SCI 后关键的细胞死亡信号通路，应作为早期治疗干预的靶点，以减轻其不良影响并促进功能恢复。替勃龙（TIB）是一种具有神经保护特性的选择性组织雌激素活性调节剂（STEAR），在一些实验模型中得到了证实。本研究旨在探讨 TIB 对 SCI 后凋亡细胞死亡和自噬的影响，并验证 TIB 是否促进运动功能恢复。在雄性 Sprague Dawley 大鼠的胸 9 水平（T9）产生中度挫伤 SCI。随后，动物每天口服 TIB 给药，并在损伤后 1、3、14 或 30 天处死。收集组织样本进行形态计量学和免疫荧光分析，以鉴定损伤部位的组织损伤和神经元百分比。还通过 Western blot 分析自噬（Beclin-1、LC3-I/LC3-II、p62）和凋亡（Caspase 3）标志物。最后，使用 BBB 量表评估运动功能。TIB 给药显著增加了保留组织的数量（<0.05），改善了运动功能的恢复（<0.001），并以时间依赖性方式调节自噬标志物的表达，同时持续抑制凋亡（<0.05）。因此，TIB 可能是 SCI 后运动功能恢复的治疗选择。
