TSPO PET detects acute neuroinflammation but not diffuse chronically activated MHCII microglia in the rat.
TSPO PET detects acute neuroinflammation but not diffuse chronically activated MHCII microglia in the rat.
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DOI：
10.1186/s13550-020-00699-x
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发表时间：
2020-09-29
期刊：
影响因子：
3.2
通讯作者：
Thiessen JD
中科院分区：
文献类型：
--
作者：
Al-Khishman NU;Qi Q;Roseborough AD;Levit A;Allman BL;Anazodo UC;Fox MS;Whitehead SN;Thiessen JD
研究神经退行性疾病中白质(WM)炎症的进展需要准确和灵敏的成像生物标志物。靶向转运蛋白(TSPO)的放射性配基被认为是神经炎症的敏感指标，但尚不清楚TSPO的表达与WM中主要组织相容性复合体II类(MHCII)分子的一致性。本研究旨在测试TSPO在前驱阿尔茨海默病和急性皮质下卒中大鼠模型中检测MHCII免疫组织化学阳性的激活的WM小胶质细胞的能力。对Fischer 344野生型(n = 12)大鼠和TgAPP21(n = 11)大鼠进行了[18F]FEPPA PET和核磁共振成像，以研究TgAPP21大鼠含量较高的MHCII激活的小胶质细胞所在的WM区的TSPO示踪剂摄取。野生型大鼠随后接受了内皮素-1(ET1)皮质下卒中，并在卒中后第7天和第28天进行成像，然后进行TSPO、GFAP、iNOS和MHCII大鼠抗原OX6的免疫组化检测。[18F]西医患者的FEPPAPET不受基因型的影响，仅在ET 1梗死区附近可见增加(P = 0.033，梗塞/小脑摄取比：基线 = 为0.94 ± 0.16；第7天 = 为2.10 ± 0.78；第28天 = 为1.77 ± 0.35)。免疫组织化学证实，只有梗死灶(第7天 = 555 ± 181；第28天 = 307 ± 153)和邻近梗死灶的白质(第7天 = 113 ± 93；第28天 = 5 ± 7)有TSPO表达。TSPO和iNOS均未检测到MHCII检测到的慢性WM小胶质细胞激活(28d：生理盐水 = 0.62 ± 0.38；卒中 = 4.30 ± 2.83；P = .029)。TSPO仅在卒中诱导的损伤和近端组织中表达，因此无法检测到WM中远端和非损伤相关的慢性激活的MHCII过度表达的小胶质细胞。这表明，神经炎症的研究，特别是在西医，将受益于MHCII敏感的放射性示踪剂。
Accurate and sensitive imaging biomarkers are required to study the progression of white matter (WM) inflammation in neurodegenerative diseases. Radioligands targeting the translocator protein (TSPO) are considered sensitive indicators of neuroinflammation, but it is not clear how well the expression of TSPO coincides with major histocompatibility complex class II (MHCII) molecules in WM. This study aimed to test the ability of TSPO to detect activated WM microglia that are immunohistochemically positive for MHCII in rat models of prodromal Alzheimer’s disease and acute subcortical stroke. Fischer 344 wild-type (n = 12) and TgAPP21 (n = 11) rats were imaged with [18F]FEPPA PET and MRI to investigate TSPO tracer uptake in the corpus callosum, a WM region known to have high levels of MHCII activated microglia in TgAPP21 rats. Wild-type rats subsequently received an endothelin-1 (ET1) subcortical stroke and were imaged at days 7 and 28 post-stroke before immunohistochemistry of TSPO, GFAP, iNOS, and the MHCII rat antigen, OX6. [18F]FEPPA PET was not significantly affected by genotype in WM and only detected increases near the ET1 infarct (P = 0.033, infarct/cerebellum uptake ratio: baseline = 0.94 ± 0.16; day 7 = 2.10 ± 0.78; day 28 = 1.77 ± 0.35). Immunohistochemistry confirmed that only the infarct (TSPO cells/mm2: day 7 = 555 ± 181; day 28 = 307 ± 153) and WM that is proximal to the infarct had TSPO expression (TSPO cells/mm2: day 7 = 113 ± 93; day 28 = 5 ± 7). TSPO and iNOS were not able to detect the chronic WM microglial activation that was detected with MHCII in the contralateral corpus callosum (day 28 OX6% area: saline = 0.62 ± 0.38; stroke = 4.30 ± 2.83; P = .029). TSPO was only expressed in the stroke-induced insult and proximal tissue and therefore was unable to detect remote and non-insult-related chronically activated microglia overexpressing MHCII in WM. This suggests that research in neuroinflammation, particularly in the WM, would benefit from MHCII-sensitive radiotracers.
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影响因子：
4.3
作者：
Weishaupt N;Zhang A;Deziel RA;Tasker RA;Whitehead SN
通讯作者：
Whitehead SN
影响因子：
7.3
作者：
Schetters STT;Gomez-Nicola D;Garcia-Vallejo JJ;Van Kooyk Y
通讯作者：
Van Kooyk Y
DOI：
10.1007/s00259-019-04403-7
发表时间：
2019-10-01
影响因子：
9.1
作者：
Tuisku, Jouni;Plaven-Sigray, Pontus;Cervenka, Simon
通讯作者：
Cervenka, Simon
DOI：
10.2967/jnumed.118.209155
发表时间：
2019-01
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Chaney A;Cropper HC;Johnson EM;Lechtenberg KJ;Peterson TC;Stevens MY;Buckwalter MS;James ML
通讯作者：
James ML
DOI：
10.1016/j.jalz.2012.05.2186
发表时间：
2013-09
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Nowrangi MA;Lyketsos CG;Leoutsakos JM;Oishi K;Albert M;Mori S;Mielke MM
通讯作者：
Mielke MM