Li Xuehan, Ma Zhixiong, Liu Xueliang, Chen Chen, Yu Ziqing, Sang Di, Wang Tongfei, Zhang Eric Erquan, Duan Guangyou, Ju Dapeng, Huang He
Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Chinese Institute for Brain Research, Beijing, China.
Cell Biol Toxicol. 2025 May 13;41(1):83. doi: 10.1007/s10565-025-10037-3.
General anesthesia (GA) is an essential clinical and surgical adjunct, widely recognized as the result of coordinated networks among numerous brain regions. Anesthetic drugs with different characteristics are associated with distinct networks of brain regions involved in anesthesia. Ciprofol, a novel intravenous anesthetic derived from structural modifications of propofol, has shown promise in clinical applications. However, the specific neuronal circuits and brain regions mediating their actions may differ. Moreover, the core brain regions that mediate the common anesthetic effects of these drugs remain unclear. In this research, we identified a central ensemble of brainstem neurons within the paramedian raphe nucleus (PMnR) using c-Fos staining in mice subjected to GA induced by continuous intravenous infusion of ciprofol and propofol. This neuronal population, primarily composed of CaMKIIa and Gad1-expressing cells, demonstrated consistent activation in reaction to ciprofol. Optogenetic activation of PMnR neurons induced a GA state under ciprofol pre-administration, while sole activation of PMnR neurons induced a motionless state in mice. In addition, conditional inhibition of these neurons resulted in resistance to GA. In summary, we highlight the PMnR as a brain target for ciprofol and propofol. Furthermore, CaMKIIa neurons in the PMnR emerge as active promoters of the anesthesia process, shedding light on a previously unrecognized key player in the intricate neural network orchestrating GA.
全身麻醉（GA）是一种重要的临床和手术辅助手段，被广泛认为是众多脑区协调网络作用的结果。具有不同特性的麻醉药物与参与麻醉的不同脑区网络相关联。环丙泊酚是一种通过对丙泊酚进行结构修饰而得到的新型静脉麻醉药，已在临床应用中显示出前景。然而，介导其作用的具体神经回路和脑区可能有所不同。此外，介导这些药物共同麻醉作用的核心脑区仍不清楚。在本研究中，我们通过对持续静脉输注环丙泊酚和丙泊酚诱导GA的小鼠进行c-Fos染色，在中缝旁核（PMnR）内鉴定出一组脑干神经元。这群神经元主要由表达CaMKIIa和Gad1的细胞组成，对环丙泊酚有一致的激活反应。在预先给予环丙泊酚的情况下，PMnR神经元的光遗传学激活诱导出GA状态，而单独激活PMnR神经元则使小鼠进入静止状态。此外，对这些神经元的条件性抑制导致对GA产生抗性。总之，我们强调PMnR是环丙泊酚和丙泊酚的脑靶点。此外，PMnR中的CaMKIIa神经元成为麻醉过程的积极推动者，为在精心编排GA的复杂神经网络中一个先前未被认识的关键角色提供了线索。
