Martínez-Moreno Carlos Guillermo, Calderón-Vallejo Denisse, Díaz-Galindo Carmen, Hernández-Jasso Irma, Olivares-Hernández Juan David, Ávila-Mendoza José, Epardo David, Balderas-Márquez Jerusa Elienai, Urban-Sosa Valeria Alejandra, Baltazar-Lara Rosario, Carranza Martha, Luna Maricela, Arámburo Carlos, Quintanar José Luis
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México.
Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, México.
Front Neurosci. 2023 Jun 9;17:1164044. doi: 10.3389/fnins.2023.1164044. eCollection 2023.
The potential for novel applications of classical hormones, such as gonadotropin-releasing hormone (GnRH) and growth hormone (GH), to counteract neural harm is based on their demonstrated neurotrophic effects in both and experimental models and a growing number of clinical trials. This study aimed to investigate the effects of chronic administration of GnRH and/or GH on the expression of several proinflammatory and glial activity markers in damaged neural tissues, as well as on sensory recovery, in animals submitted to thoracic spinal cord injury (SCI). Additionally, the effect of a combined GnRH + GH treatment was examined in comparison with single hormone administration. Spinal cord damage was induced by compression using catheter insufflation at thoracic vertebrae 10 (T10), resulting in significant motor and sensory deficits in the hindlimbs. Following SCI, treatments (GnRH, 60 μg/kg/12 h, IM; GH, 150 μg/kg/24 h, SC; the combination of both; or vehicle) were administered during either 3 or 5 weeks, beginning 24 h after injury onset and ending 24 h before sample collection. Our results indicate that a chronic treatment with GH and/or GnRH significantly reduced the expression of proinflammatory (IL6, IL1B, and iNOS) and glial activity (Iba1, CD86, CD206, vimentin, and GFAP) markers in the spinal cord tissue and improved sensory recovery in the lesioned animals. Furthermore, we found that the caudal section of the spinal cord was particularly responsive to GnRH or GH treatment, as well as to their combination. These findings provide evidence of an anti-inflammatory and glial-modulatory effect of GnRH and GH in an experimental model of SCI and suggest that these hormones can modulate the response of microglia, astrocytes, and infiltrated immune cells in the spinal cord tissue following injury.
经典激素(如促性腺激素释放激素(GnRH)和生长激素(GH))在对抗神经损伤方面具有新应用潜力,这基于它们在体外和体内实验模型中已证实的神经营养作用以及越来越多的临床试验。本研究旨在调查在遭受胸段脊髓损伤(SCI)的动物中,长期给予GnRH和/或GH对受损神经组织中几种促炎和神经胶质细胞活性标志物表达的影响,以及对感觉恢复的影响。此外,与单一激素给药相比,还研究了GnRH + GH联合治疗的效果。通过在第10胸椎(T10)处使用导管吹入法进行压迫诱导脊髓损伤,导致后肢出现明显的运动和感觉缺陷。脊髓损伤后,在损伤发生后24小时开始,在样本采集前24小时结束,在3周或5周内给予治疗(GnRH,60μg/kg/12小时,肌肉注射;GH,150μg/kg/24小时,皮下注射;两者联合;或赋形剂)。我们的结果表明,长期使用GH和/或GnRH治疗可显著降低脊髓组织中促炎标志物(IL6、IL1B和iNOS)和神经胶质细胞活性标志物(Iba1、CD86、CD206、波形蛋白和GFAP)的表达,并改善受损动物的感觉恢复。此外,我们发现脊髓尾段对GnRH或GH治疗及其联合治疗特别敏感。这些发现为GnRH和GH在SCI实验模型中的抗炎和神经胶质调节作用提供了证据,并表明这些激素可以调节脊髓损伤后脊髓组织中小胶质细胞、星形胶质细胞和浸润免疫细胞的反应。