Neuroinflammatory component of gray matter pathology in multiple sclerosis.
Neuroinflammatory component of gray matter pathology in multiple sclerosis.
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DOI：
10.1002/ana.24791
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发表时间：
2016-11
影响因子：
11.2
通讯作者：
Mainero, Caterina
中科院分区：
文献类型：
--
作者：
Herranz, Elena;Gianni, Costanza;Louapre, Celine;Treaba, Constantina A.;Govindarajan, Sindhuja T.;Ouellette, Russell;Loggia, Marco L.;Sloane, Jacob A.;Madigan, Nancy;Izquierdo-Garcia, David;Ward, Noreen;Mangeat, Gabriel;Granberg, Tobias;Klawiter, Eric C.;Catana, Ciprian;Hooker, Jacob M.;Taylor, Norman;Ionete, Carolina;Kinkel, Revere P.;Mainero, Caterina
在多发性硬化症(MS)患者中，我们利用11C-PBR28同步磁共振-正电子发射断层扫描(MR-PET)技术，对激活的小胶质细胞/巨噬细胞的标志物--18 kDa转位蛋白(TSPO)在大脑皮层、皮质病变、深部灰质(GM)、白质(WM)病变和正常白质(NAWM)中的表达进行了定量研究，以探讨神经炎症的体内病理和临床相关性。对15例继发性进展型多发性硬化症(SPMS)和12例复发缓解型多发性硬化症(RRMS)患者和14例健康对照进行了11C-PBR28MR-PET检查。MS受试者接受了7特斯拉T2*加权成像，用于皮质病变分割；神经学和认知评估。用归一化60-90分钟标准摄取值和分配体积比测量11C-PBR28结合。与对照组相比，多发性硬化症受试者表现出异常高的11C-PBR28在整个大脑中的结合，最大的增加是在皮质和皮质病变，丘脑，海马体和NAWM。MS WM病变表现为相对较轻的TSPO升高。除了TSPO表达相似的皮质病变外，SPMS对11C-PBR28的跨脑摄取高于RRMS。在MS患者中，皮质、深部GM和NAWM中11C-PBR28结合增加与神经功能障碍和认知能力减退相关；皮质变薄与丘脑TSPO水平升高相关。在多发性硬化症中，神经炎症存在于皮质、皮质病变、深层GM和NAWM，并与不良的临床结果密切相关，至少部分与神经退行性变有关。不同的炎症介导性因素可能是皮质和西医损害堆积的原因。定量测定MS中的TSPO水平可能被证明是在体内评估GM病理的炎性成分的敏感工具，特别是在皮质病变中。
In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. Fifteen secondary-progressive MS (SPMS) and 12 relapsing-remitting MS (RRMS) cases, and 14 matched healthy controls underwent 11C-PBR28 MR-PET. MS subjects underwent 7 Tesla T2*-weighted imaging for cortical lesions segmentation; neurological and cognitive evaluation. 11C-PBR28 binding was measured using normalized 60-90-minutes standardized uptake values and volume of distribution ratios. Relative to controls, MS subjects exhibited abnormally high 11C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, and closely linked to poor clinical outcome and, at least partly, to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions.
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DOI：
10.1080/13803395.2010.481620
发表时间：
2011-01-01
影响因子：
2.2
作者：
Forn, Cristina;Belenguer, Antonio;Avila, Cesar
通讯作者：
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DOI：
10.1093/jnen/62.7.723
发表时间：
2003-07-01
影响因子：
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影响因子：
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通讯作者：
Innis, Robert B.
影响因子：
5.9
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Kolb, Armin;Wehrl, Hans F.;Pichler, Bernd J.
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5.7
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Kreisl, William C.;Fujita, Masahiro;Fujimura, Yota;Kimura, Nobuyo;Jenko, Kimberly J.;Kannan, Pavitra;Hong, Jinsoo;Morse, Cheryl L.;Zoghbi, Sami S.;Gladding, Robert L.;Jacobson, Steven;Oh, Unsong;Pike, Victor W.;Innis, Robert B.
通讯作者：
Innis, Robert B.