Department of Neurosurgery, Tianjin Medical University General Hospital.
Department of Geriatrics, Tianjin Medical University General Hospital.
Neuroreport. 2024 Apr 3;35(6):352-360. doi: 10.1097/WNR.0000000000002013. Epub 2024 Feb 29.
An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1β, TNF-α, IL-10, and TGF-β. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1β and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.
免疫/炎症反应失衡加剧了创伤性脑损伤（TBI）后的继发性脑损伤，并可能使临床预后恶化。到目前为止，在临床环境中还没有找到足够的治疗途径来预防这种失衡。孕激素已被证明可调节多种疾病中的免疫/炎症反应，并在 TBI 中具有潜在的保护作用。本研究旨在探讨与免疫/炎症调节相关的孕激素对实验性 TBI 的神经保护作用。使用受控挫伤仪器在成年雄性 C57BL/6J 小鼠中建立 TBI 模型。损伤后，小鼠接受连续孕激素治疗（8mg/kg/天，腹腔注射）直至安乐死。通过 Morris 水迷宫试验评估神经功能缺损。通过干湿重法测量脑水肿。免疫组织化学染色和流式细胞术用于检查免疫/炎症细胞的数量，包括 IBA-1+小胶质细胞、髓过氧化物酶+中性粒细胞和调节性 T 细胞（Tregs）。ELISA 用于检测 IL-1β、TNF-α、IL-10 和 TGF-β 的浓度。我们的数据表明，孕激素治疗可显著改善实验性 TBI 中的神经功能缺损和脑水肿，显著增加脾脏中调节性 T 细胞的数量，并显著减少损伤脑组织中炎症细胞（小胶质细胞和中性粒细胞）的激活和浸润。此外，孕激素治疗可降低 TBI 后促炎细胞因子 IL-1β 和 TNF-α 的表达，但增加抗炎细胞因子 IL-10 的表达。这些发现表明，孕激素给药可用于调节免疫/炎症反应并改善 TBI 的结局。
