Brain grey matter volume reduction and anxiety-like behavior in lipopolysaccharide-induced chronic pulmonary inflammation rats: A structural MRI study with histological validation
Brain grey matter volume reduction and anxiety-like behavior in lipopolysaccharide-induced chronic pulmonary inflammation rats: A structural MRI study with histological validation
复制标题
脂多糖诱导的慢性肺部炎症大鼠脑灰质体积减少和焦虑样行为：具有组织学验证的结构 MRI 研究
DOI：
10.1016/j.bbi.2018.11.020
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发表时间：
2019-02-01
影响因子：
15.1
通讯作者：
Zhang, Jiaxing
中科院分区：
文献类型：
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作者：
Chen, Ji;Yan, Ya;Zhang, Jiaxing
尽管已有多项功能磁共振成像研究针对急性外周感染刺激后大脑功能的变化，但关于慢性外周感染对整个大脑形态影响的知识仍然相当有限。本研究旨在探讨外周局部感染引发慢性全身炎症后大脑结构和情绪的变化以及循环炎症标志物与大脑灰质的关系。具体来说，对患有脂多糖（LPS）诱导的慢性肺部炎症（CPI）和没有脂多糖（LPS）诱导的慢性肺部炎症（CPI）的大鼠进行体内 T2 加权 MRI。使用微分形态解剖配准通过指数谎言 (DARTEL) 增强的基于体素的形态测量来量化灰质体积，然后进行组间比较。进行旷场实验来测试 CPI 后潜在的焦虑样行为，并用 ELISA 估计炎症标志物与灰质体积相关。在图像发现的指导下，我们利用免疫荧光和尼氏染色进行了集中的组织学研究。 CPI 模型大鼠的灰质体积普遍减少。 12 种测量的炎症标记物中的 8 种呈现出不同的神经解剖学相关模式，其中三种促炎细胞因子（IL-1β、IL-6 和 TNF-α）和 CRP 最为显着。一些炎症标志物相关区域（杏仁核、CA2 和扣带皮层）灰质体积较低与更严重的焦虑样行为相关。此外，杏仁核和CA3中的灰质体积与神经胶质蛋白（S100β和Nogo-A）的表达呈负相关，而下丘脑中的灰质体积与神经细胞面积呈正相关。总体而言，我们在此展示的 MRI 观察结果所依据的神经解剖学关联模式和组织病理学可能可以作为 CPI 患者大脑和情绪缺陷的一种解释，这还将进一步对许多其他全身性炎症和炎症性自身免疫性疾病对大脑形态造成的不利影响产生新的见解。
While there have been multiple fMRI studies into the brain functional changes after acutely stimulated peripheral infection, knowledge for the effect of chronic peripheral infection on whole brain morphology is still quite limited. The present study was designed to investigate the brain structural and emotional changes after peripheral local infection initiated chronic systemic inflammation and the relationship between circulating inflammatory markers and brain grey matter. Specifically, in-vivo T2-weighted MRI was performed on rats with lipopolysaccharide (LPS)-induced chronic pulmonary inflammation (CPI) and those without. Grey matter volume was quantified using diffeomorphic anatomical registration through exponentiated lie (DARTEL) enhanced voxel-based morphometry followed by between-group comparison. Open field experiment was conducted to test the potential anxiety-like behaviors after CPI, along with the ELISA estimated inflammatory markers were correlated to grey matter volume. Guided by image findings, we undertook a focused histological investigation with immunefluorescenee and Nissl staining. A widespread decrease-of grey matter volume in CPI-model rats was revealed. 8 of the 12 measured inflammatory markers presented differential neuroanatomical correlation patterns with three of the pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) and CRP being the most notable. Lower grey matter volumes in some of the inflammatory markers related regions (amygdala, CA2 and cingulate cortex) were associated with more-severe anxiety-like behaviors. Furthermore, grey matter volumes in amygdala and CA3 were correlated negatively with the expressions of glial proteins (S100 beta and Nogo-A), while the grey matter volume in hypo-thalamus was changing positively with neural cell area. Overall, the neuroanatomical association patterns and the histopathology underpinning the MRI observations we demonstrated here would probably serve as one explanation for the cerebral and emotional deficits presented in the patients with CPI, which would furthermore yield new insights into the adverse effects the many other systemic inflammation and inflammatory autoimmune diseases would pose on brain morphology.