Compound 21, a Direct AT2R Agonist, Induces IL-10 and Inhibits Inflammation in Mice Following Traumatic Brain Injury.
Compound 21, a Direct AT2R Agonist, Induces IL-10 and Inhibits Inflammation in Mice Following Traumatic Brain Injury.
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DOI：
10.1007/s12017-021-08687-7
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发表时间：
2022-09
影响因子：
3.5
通讯作者：
Ishrat, Tauheed
中科院分区：
文献类型：
--
作者：
Ismael, Saifudeen;Ishrat, Tauheed
最近的研究表明，血管紧张素2型受体（AT 2 R）激动剂，化合物21（C21），提供神经保护和促进实验性中风的恢复。然而，C21从未在创伤性脑损伤（TBI）中进行过测试。在这里，我们的目的是检查C21是否在TBI后提供保护。在年轻成年C57 BL/6小鼠中诱导单侧皮质撞击损伤。C21（0.03 mg/kg，i.p.）在TBI后1 h和3 h给药。在神经系统严重程度评分（NSS）评估后，在TBI后24小时处死所有动物用于免疫印迹分析。与生理盐水TBI相比，C21治疗显著改善了NSS并减少了挫伤周围区域中的TBI生物标志物[高迁移率族蛋白1（HMGB 1）、水通道蛋白-4（AQ 4）]和炎症标志物[白细胞介素-1 β（IL-1β）和肿瘤坏死因子-α（TNF-α）]。此外，C21治疗诱导TBI后白细胞介素-10（IL-10）和内皮型一氧化氮合酶（eNOS）的磷酸化。C21还减弱了聚（ADP-核糖）聚合酶（PARP）和半胱天冬酶-3的促凋亡激活。这些发现支持C21对TBI的治疗潜力。
Recent studies demonstrated that the angiotensin type 2 receptor (AT2R) agonist, compound 21 (C21), provides neuroprotection and enhances recovery in experimental stroke. However, C21 has never been tested in traumatic brain injury (TBI). Here, we aim to examine whether C21 confers protection after TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. C21 (0.03 mg/kg, i.p.) was administered at 1 h and 3 h post-TBI. After neurological severity score (NSS) assessments, all animals were sacrificed for immunoblotting analysis at 24 h post-TBI. C21 treatment significantly ameliorated NSS and reduced TBI’s biomarkers [high mobility group box 1 (HMGB1), aquaporin-4 (AQ4)] and inflammatory markers [interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)] in the pericontusional areas compared to saline TBI. Further, C21 treatment induced interleukin-10 (IL-10) and phosphorylation of endothelial nitric oxide synthase (eNOS) after TBI. C21 also attenuated pro-apoptotic activation of poly (ADP-ribose) polymerase (PARP) and caspase-3. These findings support the therapeutic potential of C21 against TBI.
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影响因子：
3.6
作者：
Mirzahosseini G;Ismael S;Ahmed HA;Ishrat T
通讯作者：
Ishrat T
影响因子：
5
作者：
Fouda AY;Pillai B;Dhandapani KM;Ergul A;Fagan SC
通讯作者：
Fagan SC
影响因子：
6.3
作者：
Ishrat, Tauheed;Fouda, Abdelrahman Y.;Fagan, Susan C.
通讯作者：
Fagan, Susan C.
影响因子：
6.1
作者：
Namsolleck, Pawel;Boato, Francesco;Steckelings, U. Muscha
通讯作者：
Steckelings, U. Muscha
影响因子：
2.4
作者：
Cuthbert, Jeffrey P.;Harrison-Felix, Cynthia;Whiteneck, Gale G.
通讯作者：
Whiteneck, Gale G.