研究已确认孕酮（P4）对创伤性脑损伤（TBI）具有益处。本研究通过其受体研究了P4对TBI的有益作用，以及孕酮受体（PRs）是否可以通过PI3K / Akt通路调节TBI。使用Marmarou方法在卵巢切除的大鼠中诱导扩散性TBI。TBI诱导后30分钟给予P4（1.7mg / kg）或载体（油）治疗。此外，TBI诱导和P4注射前注射了RU486（PR拮抗剂）和其载体（DMSO）。在TBI后24小时评估了大脑埃文斯蓝含量，大脑含水量（WC），各种氧化应激参数，IL-1β水平，肿瘤坏死因子-α（TNF-α），组织病理学变化，以及大脑中磷酸化Akt（p-Akt）和PI3K的表达。在TBI之前和之后的不同时间测量了兽医逗号量表（VCS）。结果显示，P4增加了VCS并降低了大脑WC，氧化应激，TNF-α和IL-1β水平。RU486抑制了P4对这些指标的有益作用。此外，RU486阻止了P4引起的大脑水肿，炎症和细胞凋亡的减少。此外，TBI后的P4增加了大脑中PI3K / p-Akt蛋白的表达。RU486消除了P4对PI3K / p-Akt表达的影响。根据这些发现，PRs作为P4对氧化应激，促炎因子水平和神经病理结果的神经保护性特性的关键调节因子。PRs还在调节P4的PI3K / p-Akt表达和非基因组功能中发挥重要作用。根据这些发现，本研究显示PRs在TBI中对孕酮的神经保护性特性，促炎因子水平和神经学结果起到了关键调节作用。PRs还在调节PI3K / p-Akt的表达和孕酮的非基因组功能中发挥重要作用。© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Studies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway.Marmarou method was utilized to induce diffuse TBI in ovariectomized rats. P4 (1.7 mg/kg) or the vehicle (oil) was administered 30 min after TBI induction. Moreover, RU486 (PR antagonist) and its vehicle (DMSO) were injected before TBI induction and P4 injection. Brain Evans blue content, brain water content (WC), various oxidative stress parameters, IL-1β levels, tumor necrosis factor-α (TNF-α), histopathological alterations, and also phosphorylated Akt (p-Akt) and PI3K expressions in the brain were assessed 24 h after TBI. The veterinary comma scale (VCS) was measured before and after TBI at different times.The findings revealed that P4 caused an increase in VCS and a decrease in brain WC, oxidative stress, TNF-α and IL-1β levels. RU486 inhibited the beneficial effects of P4 on these indices. Moreover, RU486 prevented the reduction of brain edema, inflammation, and apoptosis caused by P4. Moreover, P4 following TBI increased the expression of PI3K/p-Akt protein in the brain. RU486 eliminated the effects of P4 on PI3K/p-Akt expression.According to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro-inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p-Akt expression and nongenomic function of P4.© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.