Physiology Research Center, Ahwaz University of Medical Sciences, Ahwaz, Iran.
J Neurotrauma. 2013 Jan 1;30(1):47-54. doi: 10.1089/neu.2010.1686. Epub 2012 Nov 16.
Following a traumatic brain injury (TBI), excessive release of proinflammatory cytokines is the major cause of cerebral edema and neuronal loss. This study was designed to examine changes in concentrations of some proinflammatory cytokines-including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β)-in a rat model of TBI in which the animals were treated with different doses of estrogen or progesterone 6 and 24 h after the TBI. Adult female rats were divided into 14 groups. Hormones or vehicle were given intraperitoneally 30 min after a moderate TBI was induced by the Marmarou method. The levels of proinflammatory cytokines in brain were measured at 6 and 24 h after the TBI. A high dose of estrogen (E2) or a low dose of progesterone (P1) increased brain levels of IL-1β 52.7% and 79.2% respectively at 6 h after the TBI. By 24h, IL-1β levels in the brain were 27.5% and 27% lower following administration of estrogen low dose (E1) or E2, respectively. High-dose administration of progesterone reduced brain levels of IL-6 to 45.9% at 6 h after the TBI, and P1 and E1 treatment significantly decreased IL-6 levels at 24 h. Brain levels of TNF-α were 72.5% lower at 6 h after the TBI following P2 treatment and 48.5% higher at 24 hrs following treatment with E2. The levels of TGF-β were also 3.37 times higher 24 h after the TBI following treatment with E1. Both doses of the hormones tested increases TGF-β levels 6 h after the TBI. Based on our findings, we conclude that progesterone and estrogen influence the levels of proinflammatory cytokines either at the primary or secondary stages after a TBI. Accordingly, this study suggests a mechanism by which hormones reduce cerebral edema.
颅脑损伤（TBI）后，促炎细胞因子的过度释放是脑水肿和神经元丢失的主要原因。本研究旨在观察 TBI 大鼠模型中某些促炎细胞因子（包括白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β））浓度的变化，其中动物在 TBI 后 6 和 24 小时接受不同剂量的雌激素或孕激素治疗。将成年雌性大鼠分为 14 组。用 Marmarou 法诱导中度 TBI 后 30 分钟，经腹腔给予激素或载体。TBI 后 6 和 24 小时测量脑内促炎细胞因子水平。TBI 后 6 小时，高剂量雌激素（E2）或低剂量孕激素（P1）分别使脑内 IL-1β 水平增加 52.7%和 79.2%。到 24 小时时，E1 或 E2 低剂量给药后，脑内 IL-1β 水平分别降低 27.5%和 27%。高剂量孕激素给药使脑内 IL-6 水平在 TBI 后 6 小时降低至 45.9%，P1 和 E1 治疗在 24 小时时显著降低 IL-6 水平。P2 治疗后，TBI 后 6 小时脑内 TNF-α 水平降低 72.5%，E2 治疗后 24 小时升高 48.5%。TBI 后 24 小时，E1 治疗后 TGF-β 水平升高 3.37 倍。两种测试激素剂量均在 TBI 后 6 小时增加 TGF-β 水平。根据我们的发现，我们得出结论，孕激素和雌激素在 TBI 后原发性或继发性阶段影响促炎细胞因子的水平。因此，本研究提出了激素减轻脑水肿的机制。
