Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.
Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.
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DOI：
10.1002/hbm.26491
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发表时间：
2023-12-01
影响因子：
4.8
通讯作者：
Murphy, Barbara A.
中科院分区：
文献类型：
--
作者：
Schoenberg, Poppy L. A.;Song, Alexander K.;Mohr, Emily M.;Rogers, Baxter P.;Peterson, Todd E.;Murphy, Barbara A.
关键词：
中枢神经系统（CNS）内长时间的炎症表达被大脑识别为“疾病”的分子信号，对血脑屏障、脑脊髓屏障、血脑脊液屏障、神经轴突结构、神经递质活性、突触可塑性、神经内分泌功能以及由此产生的全身症状产生连锁反应。人们一致认为，与癌症和癌症治疗相关的炎症过程强调了大部分幸存者中存在的全身症状，尽管这一概念很大程度上是来自不同和间接证据和/或临床轶事报告的理论。我们进行了一项概念验证研究，首次使用 TSPO 结合 PET 示踪剂 [11C]-PBR28 来可视化小胶质细胞激活，将出现慢性全身症状和集中炎症或神经炎症的晚期非 CNS 癌症幸存者联系起来。我们比较了 10 名非 CNS 癌症幸存者和 10 名匹配的健康对照者的 PBR28 SUVR。我们的数据显示（1）与健康对照相比，晚期非中枢神经系统/中枢神经系统癌症幸存者尾状、颞叶和枕叶区域的小胶质细胞活化显着更高； (2)癌症幸存者中神经炎症的增加并不伴随着外周炎症的血浆细胞因子标志物的显着差异； (3) 神经炎症的增加并不伴随各向异性分数的降低，这表明白质微结构完整性完整，这是神经血管纤维束组织的标志； (4)癌症幸存者慢性全身症状的出现与小胶质细胞激活显着相关。我们提出了第一个数据，从经验上支持非中枢神经系统癌症幸存者，特别是那些先前患有头颈癌的患者的外周到中心炎症反应的概念。在癌症/其治疗引起的最初外周炎症消退后，在某些情况下，中枢神经系统会发生损伤/中毒，从而导致慢性全身症状。在这里，我们提供的数据首次将小胶质细胞激活（或神经炎症）的存在与非中枢神经系统癌症幸存者的慢性全身症状的表现联系起来。
Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of “sickness”, that has knock‐on effects to the blood–brain barrier, brain‐spinal barrier, blood‐cerebrospinal fluid barrier, neuro‐axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof‐of‐concept study to link for the first time late non‐CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO‐binding PET tracer [11C]‐PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non‐CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non‐central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral‐to‐centralized inflammatory response in non‐CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms. Here we present data that links for the first time the presence of microglial activation (or neuroinflammation) with the presentation of chronic systemic symptoms in non‐central nervous system cancer survivors.
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影响因子：
3.3
作者：
Cai LY;Yang Q;Hansen CB;Nath V;Ramadass K;Johnson GW;Conrad BN;Boyd BD;Begnoche JP;Beason-Held LL;Shafer AT;Resnick SM;Taylor WD;Price GR;Morgan VL;Rogers BP;Schilling KG;Landman BA
通讯作者：
Landman BA
影响因子：
5.6
作者：
Dupont AC;Largeau B;Santiago Ribeiro MJ;Guilloteau D;Tronel C;Arlicot N
通讯作者：
Arlicot N
DOI：
10.1002/dad2.12128
发表时间：
2020
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
--
作者：
Edwin TH;Henjum K;Nilsson LNG;Watne LO;Persson K;Eldholm RS;Saltvedt I;Halaas NB;Selbæk G;Engedal K;Strand BH;Knapskog AB
通讯作者：
Knapskog AB
DOI：
10.1016/j.jmr.2011.09.022
发表时间：
1996-06-01
期刊：
JOURNAL OF MAGNETIC RESONANCE SERIES B
影响因子：
--
作者：
Basser, PJ;Pierpaoli, C
通讯作者：
Pierpaoli, C
影响因子：
5.7
作者：
Dale, AM;Fischl, B;Sereno, MI
通讯作者：
Sereno, MI