In vivo multimodal imaging of adenosine A(1) receptors in neuroinflammation after experimental stroke.
In vivo multimodal imaging of adenosine A(1) receptors in neuroinflammation after experimental stroke.
复制标题
实验中风后神经炎症中腺苷A（1）受体的体内多模式成像。
DOI：
10.7150/thno.51046
复制
发表时间：
2021
期刊：
影响因子：
12.4
通讯作者：
Martín A
中科院分区：
文献类型：
--
作者：
Joya A;Ardaya M;Montilla A;Garbizu M;Plaza-García S;Gómez-Vallejo V;Padro D;Gutiérrez JJ;Rios X;Ramos-Cabrer P;Cossío U;Pulagam KR;Higuchi M;Domercq M;Cavaliere F;Matute C;Llop J;Martín A
腺苷A1受体（A1ARs）是很有前途的成像生物标志物和治疗中风的靶点。然而，到目前为止，A1ARs在缺血性损伤及其随后的神经炎症反应中的作用还很少被探索。方法：本研究采用正电子发射断层扫描(PET) + [18F]CPFPX和免疫组织化学（IHC）检测短暂性大脑中动脉闭塞（MCAO）后A1ARs的表达。此外，通过磁共振成像（MRI）、PET成像([18F]DPA-714 （TSPO）和[18F]FLT（细胞增殖）、免疫组化（IHC）和神经功能研究评估A1ARs对脑卒中炎症的药理调节作用。结果：在缺血区域，[18F]CPFPX信号和免疫组化显示脑缺血后小胶质细胞和浸润性白细胞中A1ARs过表达。用A1AR激动剂ENBA治疗的缺血大鼠在脑缺血后第7天[18F]DPA-714和[18F]FLT信号强度均显著降低，IHC结果证实了这一特征。此外，通过T2W-MRI测量，A1ARs的激活促进了脑部病变的减少，并改善了包括运动、感觉和反射反应在内的神经系统预后。这些结果首次展示了大鼠脑缺血后A1ARs的体内PET成像以及[18F]FLT在评估治疗后胶质细胞增殖反应中的应用。结论：值得注意的是，这些数据为A1ARs在大鼠实验性脑卒中后驻留胶质细胞的激活以及小胶质细胞和巨噬细胞的新生增殖的控制中发挥了关键作用提供了证据。
Adenosine A1 receptors (A1ARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of A1ARs on ischemic damage and its subsequent neuroinflammatory response has been scarcely explored so far. Methods: In this study, the expression of A1ARs after transient middle cerebral artery occlusion (MCAO) was evaluated by positron emission tomography (PET) with [18F]CPFPX and immunohistochemistry (IHC). In addition, the role of A1ARs on stroke inflammation using pharmacological modulation was assessed with magnetic resonance imaging (MRI), PET imaging with [18F]DPA-714 (TSPO) and [18F]FLT (cellular proliferation), as well as IHC and neurofunctional studies. Results: In the ischemic territory, [18F]CPFPX signal and IHC showed the overexpression of A1ARs in microglia and infiltrated leukocytes after cerebral ischemia. Ischemic rats treated with the A1AR agonist ENBA showed a significant decrease in both [18F]DPA-714 and [18F]FLT signal intensities at day 7 after cerebral ischemia, a feature that was confirmed by IHC results. Besides, the activation of A1ARs promoted the reduction of the brain lesion, as measured with T2W-MRI, and the improvement of neurological outcome including motor, sensory and reflex responses. These results show for the first time the in vivo PET imaging of A1ARs expression after cerebral ischemia in rats and the application of [18F]FLT to evaluate glial proliferation in response to treatment. Conclusion: Notably, these data provide evidence for A1ARs playing a key role in the control of both the activation of resident glia and the de novo proliferation of microglia and macrophages after experimental stroke in rats.
登录
查看更多内容
影响因子：
3.1
作者：
Kroll, Tina;Elmenhorst, David;Bauer, Andreas
通讯作者：
Bauer, Andreas
影响因子：
2.5
作者：
Dobre, Mircea C.;Ugurbil, Kamil;Marjanska, Malgorzata
通讯作者：
Marjanska, Malgorzata
影响因子：
3.6
作者：
BRUNS, RF;FERGUS, JH;HUANG, CC
通讯作者：
HUANG, CC
影响因子：
5.7
作者：
Bauer, A;Holschbach, MH;Zilles, K
通讯作者：
Zilles, K
影响因子：
3
作者：
Ortuño JE;Ledesma-Carbayo MJ;Simões RV;Candiota AP;Arús C;Santos A
通讯作者：
Santos A