Hubei University of Medicine, Shiyan, China.
Department of Orthopedics, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, China.
Cell Mol Biol (Noisy-le-grand). 2024 Jan 31;70(1):213-218. doi: 10.14715/cmb/2024.70.1.29.
Neuroinflammation induced by microglia following spinal cord injury (SCI) leads to secondary neurologic injury. Androgens including testosterone and dihydrotestosterone (DHT) show as endogenous neuroprotective factors against multiple neurologic diseases, while their therapeutic role in SCI-induced neuroinflammation and underlying mechanism remains elusive. In the study, we aimed to investigate the role of DHT against microglia-induced neuroinflammation in SCI and evaluate its protective treatment. BV2 cells were activated by neuroinflammation via LPS in vitro. Adult male C57BL/6 mice were used to establish the SCI model. BV2 cells and SCI mice were administrated DHT. Microglia activation, pro-inflammatory factors, p38 and p65 phosphorylation, glial scar, fibrotic scar, histology, and locomotor function recovery were measured, respectively. We demonstrated that DHT administration attenuates neuroinflammation in microglia through inhibition of p38 and p65 pathways. Moreover, DHT reduces microglia and astrocyte accumulation, cord fibrosis and histologic damage. Besides, DHT ameliorates locomotor functional recovery after SCI. DHT is verified to play a neuroprotective role in SCI, which fights against neuroinflammation by inhibition of p38 and p65 pathways. Therefore, Mel is defined as a promising factor in protecting neural tissue after SCI.
小胶质细胞引发的脊髓损伤（SCI）后的神经炎症会导致继发性神经损伤。雄激素包括睾酮和二氢睾酮（DHT），被认为是多种神经疾病的内源性神经保护因子，但其在 SCI 诱导的神经炎症中的治疗作用及其潜在机制仍不清楚。在这项研究中，我们旨在研究 DHT 对 SCI 中小胶质细胞诱导的神经炎症的作用，并评估其保护治疗作用。体外通过 LPS 激活 BV2 细胞的神经炎症。使用成年雄性 C57BL/6 小鼠建立 SCI 模型。给予 DHT 治疗 BV2 细胞和 SCI 小鼠。分别测量小胶质细胞激活、促炎因子、p38 和 p65 磷酸化、神经胶质瘢痕、纤维性瘢痕、组织学和运动功能恢复。结果表明，DHT 通过抑制 p38 和 p65 通路减轻小胶质细胞中的神经炎症。此外，DHT 减少小胶质细胞和星形胶质细胞的积累、脊髓纤维化和组织学损伤。此外，DHT 改善 SCI 后的运动功能恢复。DHT 被证实对 SCI 具有神经保护作用，它通过抑制 p38 和 p65 通路对抗神经炎症。因此，Mel 被定义为一种有前途的保护 SCI 后神经组织的因子。
