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.

最近的研究表明，血管紧张素 2 型受体 (AT2R) 激动剂化合物 21 (C21) 可提供神经保护并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，我们旨在检查 C21 是否在 TBI 后提供保护。在年轻的成年 C57BL/6 小鼠中诱导了单侧皮质撞击损伤。C21 (0.03 mg/kg, ip) 在 TBI 后 1 小时和 3 小时给药。在评估神经严重程度评分 (NSS) 后，在 TBI 后 24 小时处死所有动物进行免疫印迹分析。C21 治疗显着改善 NSS 并降低 TBI 的生物标志物 [高迁移率组框 1 (HMGB1)、水通道蛋白-4 (AQ4)] 和炎症标志物 [interlukin-1β (IL-1β) 和肿瘤坏死因子-α (TNF-α)]与盐水 TBI 相比，在挫伤周围区域。更远，C21 治疗在 TBI 后诱导白细胞介素 10 (IL-10) 和内皮一氧化氮合酶 (eNOS) 的磷酸化。C21 还减弱了聚 (ADP-核糖) 聚合酶 (PARP) 和 caspase-3 的促凋亡激活。这些发现支持 C21 对 TBI 的治疗潜力。