Department of Radiology, Fujita Health University, Kutsukake, Toyoake, Aichi, Japan.
Ann Nucl Med. 2010 Apr;24(3):163-9. doi: 10.1007/s12149-009-0339-0. Epub 2010 Jan 26.
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, [(11)C]PK11195, has been used for imaging of the activation of microglia in vivo. We evaluated whether [(11)C]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 [(11)C]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 (TNFalpha, IL-1beta) 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 (TNFalpha, IL-1beta) than the non-treated group indicating that further activation was induced by LPS treatment.
The results suggest that intensity of PBR signals in [(11)C]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.
小胶质细胞从正常静息状态向激活状态的转变与外周苯二氮䓬受体（PBR）的表达增加有关。PBR 的表达程度取决于小胶质细胞激活的程度。PBR 配体 [(11)C]PK11195 已被用于体内小胶质细胞激活的成像。我们评估了 [(11)C]PK11195 PET 是否可以在大鼠脑炎症人工损伤模型中指示小胶质细胞激活的差异，这种差异存在于未治疗和脂多糖（LPS）治疗之间。
在第 1 天，将少量绝对乙醇注入大鼠右侧纹状体（ST）以产生人工脑损伤。在第 3 天，进行 MRI 扫描以评估并选择显示出相似程度脑损伤的大鼠。然后，通过腹腔内给药 LPS 或载体。在第 4 天，在 [(11)C]PK11195 静脉推注后进行 PET 扫描。评估了 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 0 至 60 分钟时右和左纹状体的积分摄取比作为 PBR 分布容积（V（60））的估计值。通过异硫氰酸荧光素-B4 染色和 RT-PCR 分别评估激活的小胶质细胞的数量和炎症细胞因子（TNFalpha、IL-1beta）的 mRNA 表达。
LPS 组的右/左 ST V（60）比值明显高于非-LPS 组（P <0.03）。尽管两组之间激活的小胶质细胞数量没有差异，但 LPS 组的炎症细胞因子（TNFalpha、IL-1beta）表达高于未治疗组，表明 LPS 治疗诱导了进一步的激活。
结果表明，[(11)C]PK11195 PET 中 PBR 信号的强度可能与小胶质细胞激活的程度有关，而不是激活的小胶质细胞的数量，至少在人工脑损伤模型中是这样。
