Neuroinflammation plays a vital role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The hypothesis of this study was that activation of melanocortin 1 receptor (MC1R) with BMS-470539 attenuates EBI by suppression of neuroinflammation after SAH. We utilized BMS-470539, MSG-606, and MRT-68601 to verify the neuroprotective effects of MC1R. We evaluated brain water content, short-term and long-term neurobehavior after SAH. Western blotting and immunofluorescence staining were utilized to assess the changes of protein levels. The results of western blotting suggested that the expressions of MC1R, phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK), and phosphorylated-TANK binding kinase 1 (p-TBK1) were increased and reached their peak points at 24 h following SAH. Moreover, BMS-470539 treatment notably attenuated neurological deficits caused by SAH, and also notably improved long-term spatial learning and memory abilities after SAH. The underlying mechanisms of the neuroprotection of BMS-470539 involved the suppression of microglia activation, promotion of CD206+ microglia transformation and reduction of neutrophil infiltration by increasing the levels of p-AMPK and p-TBK1 while decreasing the levels of NF-κB, IL-1β, and TNFα. The neuroprotective effects of BMS-470539 were significantly abolished by MSG-606 and MRT-68601. The activation of MC1R with BMS-470539 notably attenuates EBI after SAH by suppression of microglial activation and neutrophil infiltration via the AMPK/TBK1/NF-κB signaling pathway.

中文翻译：

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黑皮质素 1 受体的激活通过 AMPK/TBK1/NF-κB 通路抑制神经炎症，减轻蛛网膜下腔出血大鼠模型的早期脑损伤。


神经炎症在蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）中起着至关重要的作用。本研究的假设是，BMS-470539 激活黑皮质素 1 受体 (MC1R) 可通过抑制 SAH 后的神经炎症来减轻 EBI。我们利用 BMS-470539、MSG-606 和 MRT-68601 来验证 MC1R 的神经保护作用。我们评估了 SAH 后的脑含水量、短期和长期神经行为。利用蛋白质印迹和免疫荧光染色来评估蛋白质水平的变化。 Western blotting结果显示，MC1R、磷酸化腺苷酸激活蛋白激酶（p-AMPK）和磷酸化TANK结合激酶1（p-TBK1）的表达增加，并在SAH后24 h达到峰值。 。此外，BMS-470539 治疗显着减轻了 SAH 引起的神经功能缺损，并显着改善了 SAH 后的长期空间学习和记忆能力。 BMS-470539 神经保护的潜在机制涉及通过增加 p-AMPK 和 p-TBK1 水平同时降低 NF-κB、IL- 水平来抑制小胶质细胞活化、促进 CD206+ 小胶质细胞转化和减少中性粒细胞浸润。 1β和TNFα。 BMS-470539 的神经保护作用被 MSG-606 和 MRT-68601 显着消除。 BMS-470539 激活 MC1R，通过 AMPK/TBK1/NF-κB 信号通路抑制小胶质细胞激活和中性粒细胞浸润，显着减弱 SAH 后的 EBI。