Department of Pediatrics, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Comp Immunol Microbiol Infect Dis. 2013 Mar;36(2):137-48. doi: 10.1016/j.cimid.2012.11.002. Epub 2012 Dec 27.
Acute bacterial meningitis (ABM) is a serious disease with severe neurological sequelae. The intense calcium-mediated microglial activation and subsequently pro-inflammatory cytokine release plays an important role in eliciting ABM-related oxidative damage. Considering resveratrol possesses significant anti-inflammatory and anti-oxidative properties, the present study aims to determine whether resveratrol would exert beneficial effects on hippocampal neurons following ABM. ABM was induced by inoculating Klebsiella pneumoniae into adult rats intraventricularly. The time-of-flight secondary ion mass spectrometry (TOF-SIMS), Griffonia simplicifolia isolectin-B4 (GSA-IB4) and ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry, enzyme-linked immunosorbent assay as well as malondialdehyde (MDA) measurement were used to examine the calcium expression, microglial activation, pro-inflammatory cytokine level, and extent of oxidative stress, respectively. In ABM rats, strong calcium signaling associated with enhanced microglial activation was observed in hippocampus. Increased microglial expression was coincided with intense production of pro-inflammatory cytokines and oxidative damage. However, in rats receiving resveratrol after ABM, the calcium intensity, microglial activation, pro-inflammatory cytokine and MDA levels were all significantly decreased. Quantitative data showed that much more hippocampal neurons were survived in resveratrol-treated rats following ABM. As resveratrol successfully rescues hippocampal neurons from ABM by suppressing the calcium-mediated microglial activation, therapeutic use of resveratrol may act as a promising strategy to counteract the ABM-induced neurological damage.
急性细菌性脑膜炎（ABM）是一种严重的疾病，可导致严重的神经后遗症。强烈的钙介导的小胶质细胞激活以及随后的促炎细胞因子释放，在引发 ABM 相关氧化损伤中起重要作用。鉴于白藜芦醇具有显著的抗炎和抗氧化特性，本研究旨在确定白藜芦醇是否会对 ABM 后海马神经元产生有益影响。通过向成年大鼠脑室内接种肺炎克雷伯菌来诱导 ABM。使用飞行时间二次离子质谱（TOF-SIMS）、相思豆凝集素-B4（GSA-IB4）和离子化钙结合衔接分子 1（Iba1）免疫组织化学、酶联免疫吸附测定以及丙二醛（MDA）测量，分别检测钙表达、小胶质细胞激活、促炎细胞因子水平和氧化应激程度。在 ABM 大鼠中，观察到海马中与增强的小胶质细胞激活相关的强烈钙信号。小胶质细胞表达增加伴随着强烈的促炎细胞因子产生和氧化损伤。然而，在 ABM 后接受白藜芦醇治疗的大鼠中，钙强度、小胶质细胞激活、促炎细胞因子和 MDA 水平均显著降低。定量数据显示，ABM 后接受白藜芦醇治疗的大鼠中有更多的海马神经元存活。由于白藜芦醇通过抑制钙介导的小胶质细胞激活成功挽救 ABM 后的海马神经元，因此白藜芦醇的治疗用途可能是对抗 ABM 引起的神经损伤的一种有前途的策略。
