Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats
Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats
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DOI：
10.1007/s12149-009-0339-0
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发表时间：
2010-04-01
影响因子：
2.6
通讯作者：
Sawada, Makoto
中科院分区：
文献类型：
--
作者：
Ito, Fumitaka;Toyama, Hiroshi;Sawada, Makoto
小胶质细胞从正常静息状态到激活状态的转变与外周苯二氮卓受体（PBR）表达的增加有关。PBR表达的程度取决于小胶质细胞活化的水平。PBR配体[C-11] PK 11195已用于体内小胶质细胞活化的成像。我们评估了[C-11] PK 11195 PET是否可以在大鼠脑炎症的人工损伤模型中显示未处理和脂多糖（LPS）处理之间小胶质细胞活化的差异。在第3天，进行MRI扫描以评价和选择显示相似程度脑损伤的大鼠。然后腹腔内施用LPS或媒介物。第4天，在推注[C-11] PK 11195后进行PET扫描。评价了11只大鼠（7只给予LPS的大鼠，4只未给予LPS的大鼠）。我们使用从0到60分钟左右纹状体积分的摄取比率作为PBR分布体积（V（60））的估计值。结果：LPS组大鼠左/右ST V（60）比值显著高于非LPS组（P <0.03），LPS组大鼠左/右ST V（60）比值显著高于非LPS组（P < 0.03），LPS组大鼠左/右ST V（60）比值显著高于非LPS组（P < 0.03）。虽然两组活化小胶质细胞数量无明显差异，但LPS组炎性细胞因子表达较高（TNF α，结果表明，LPS处理后[C-11]中PBR信号的强度明显高于未处理组，表明LPS处理可诱导进一步的激活。PK 11195 PET可能与小胶质细胞活化水平有关，而不是至少在人工脑损伤模型中活化的小胶质细胞的数量。
The transition of microglia from the normal resting state to the activated state is associated with an increased expression of peripheral benzodiazepine receptors (PBR). The extent of PBR expression is dependent on the level of microglial activation. A PBR ligand, [C-11]PK11195, has been used for imaging of the activation of microglia in vivo. We evaluated whether [C-11]PK11195 PET can indicate differences of microglial activation between no treatment and lipopolysaccharide (LPS) treatment in a rat artificial injury model of brain inflammation.On day 1, a small aliquot of absolute ethanol was injected into the rat right striatum (ST) to produce artificial brain injury. On day 3, MRI scans were performed to evaluate and select rats showing a similar degree of brain injury. Then LPS or vehicle was administered intraperitoneally. On day 4, PET scans were performed after a bolus injection of [C-11]PK11195. Eleven rats (7 LPS administered rats, 4 LPS non-administered rats) were evaluated. We used uptake ratios of the integral of right and left striatum from 0 to 60 min as an estimate of PBR distribution volume (V (60)). The number of activated microglia and mRNA expression of inflammatory cytokines (TNF alpha, IL-1 beta) were assessed by isolectin-B4 staining and RT-PCR, respectively.Right/left ST V (60) ratios of LPS group were significantly higher than those of non-LPS group (P < 0.03). Although there were no significant differences in the number of activated microglia between the two groups, LPS group showed higher expression of inflammatory cytokines (TNF alpha, IL-1 beta) than the non-treated group indicating that further activation was induced by LPS treatment.The results suggest that intensity of PBR signals in [C-11]PK11195 PET may be related to the level of microglial activation rather than the number in activated microglia at least in an artificial brain injury model.