Center for Immunochemistry, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
Brain Res Bull. 2011 Jul 15;85(6):403-9. doi: 10.1016/j.brainresbull.2011.04.007. Epub 2011 May 7.
Traumatic brain injury (TBI) is a major cause of disability in civilians and military personnel worldwide that is caused by the acceleration force of a primary shockwave, blast wind or the force of a direct contact. Following the primary injury, secondary injury is caused by activation of the immune response due to an influx of neuro-inflammatory cells, increased production of inflammatory cytokines, and edema. In ischemia models pre-conditioning with lipopolysaccharide (LPS) has been shown to be neuroprotective, and post-injury conditioning with LPS was found to be protective in a spinal cord and an acute brain injury model. In this study, we utilized an in vitro scratch model of TBI to assess the effect of post-injury treatment with Escherichia coli LPS and Neisseria meningitidis lipooligosaccharide (LOS) on cell death and cytokine induction by assessing the level of lactate dehydrogenase released from cells and rat multiplex cytokine assays. Our results showed that post-injury treatment of C6 glioma cells with either the LPS or the LOS reduced cell death when compared to scratched controls treated with media only. Post-injury treatment of the primary mixed neuronal cultures with LPS reduced cell death and resulted in a significant up-regulation in IL-10 when compared to controls. With LOS post-scratch treatment of the primary cell cultures, we found that IL-1α, IL-1β, IL-6, and TNF-α were significantly upregulated in addition to IL-10 compared to the media-only controls. The results strongly support additional testing of the neuroprotective ability of post-injury treatment with LPS or LOS in models of TBI.
创伤性脑损伤（TBI）是全球范围内导致平民和军事人员残疾的主要原因，其由原发性冲击波、爆炸风或直接接触的加速力引起。原发性损伤后，继发性损伤是由神经炎症细胞的涌入、炎症细胞因子的产生增加和水肿引起的免疫反应激活引起的。在缺血模型中，脂多糖（LPS）预处理已被证明具有神经保护作用，而 LPS 损伤后处理在脊髓和急性脑损伤模型中被发现具有保护作用。在这项研究中，我们利用体外 TBI 划痕模型来评估损伤后用大肠杆菌 LPS 和脑膜炎奈瑟菌脂寡糖（LOS）处理对细胞死亡和细胞因子诱导的影响，方法是评估从细胞释放的乳酸脱氢酶水平和大鼠多重细胞因子测定。我们的结果表明，与仅用培养基处理的划痕对照相比，C6 神经胶质瘤细胞损伤后用 LPS 或 LOS 处理可降低细胞死亡。与对照相比，损伤后用 LPS 处理原代混合神经元培养物可降低细胞死亡并导致 IL-10 的显著上调。用 LOS 处理原代细胞培养物后，与仅用培养基处理的对照相比，我们发现除了 IL-10 之外，IL-1α、IL-1β、IL-6 和 TNF-α的表达也显著上调。这些结果强烈支持在 TBI 模型中进一步测试损伤后用 LPS 或 LOS 进行神经保护的能力。
