Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Anaesthesia and Operation Centre, Chinese PLA General Hospital, Fourth Clinical Centre, Beijing, China.
Br J Anaesth. 2019 Oct;123(4):497-505. doi: 10.1016/j.bja.2019.07.005. Epub 2019 Aug 6.
Orexin can facilitate emergence after general anaesthesia via multiple neural pathways. Dopaminergic neurones in the ventral tegmental area (VTA) participate in behavioural arousal from anaesthesia. We investigated the regulation of dopaminergic VTA neurones by orexinergic neurones during emergence from general anaesthesia.
Orexins were microinjected into the VTA to determine the effects on isoflurane anaesthesia induction, emergence, and maintenance. Orexin receptors and dopaminergic neurones in the VTA were identified using immunofluorescence. Orexinergic terminals in the VTA were optogenetically regulated to detect the endogenous orexin-mediated regulation of dopaminergic neurones during anaesthesia in Hcrt rats.
Injection of orexin-A (100 pmol) into the VTA reduced emergence time [from 949 (118) to 727 (101) s; P=0.0058] and reduced the electroencephalographic burst-suppression ratio (BSR) (26.6 [10.2]% vs 44.3 [6.8]%; P=0.0027) during isoflurane anaesthesia. The percentage of dopaminergic neurones that expressed either orexin-1 receptor or orexin-2 receptor was 73.4 (5.0)% and 74.4 (62.4)%, respectively. Optogenetic activation of orexinergic projections to the VTA reduced the BSR (from 40.5 [2.7]% to 22.4 [11.8]%; P=0.0019) and facilitated emergence (915 [89] vs 685 [68] s; P=0.0026), whereas optical inhibition prolonged the time to wakefulness (from 941 [92] to 1279 [250] s; P=0.011). Dopaminergic neurones in the VTA showed increased firing frequency (387 [78]% of control, P=0.005) after bath application of orexin-A.
Orexin promotes emergence from isoflurane anaesthesia through activation of dopaminergic neurones in the VTA.
orexin 可通过多种神经通路促进全身麻醉后的苏醒。腹侧被盖区（VTA）中的多巴胺能神经元参与从麻醉中苏醒的行为唤醒。我们研究了全身麻醉苏醒过程中 orexin 能神经元对 VTA 多巴胺能神经元的调节作用。
将 orexin 微注射到 VTA 中，以确定其对异氟醚麻醉诱导、苏醒和维持的影响。使用免疫荧光法鉴定 VTA 中的 orexin 受体和多巴胺能神经元。用光遗传学调节 VTA 中的 orexin 能末梢，以检测在 Hcrt 大鼠中麻醉期间内源性 orexin 对多巴胺能神经元的调节作用。
将 orexin-A（100 pmol）注射到 VTA 中，减少了苏醒时间[从 949（118）到 727（101）s；P=0.0058]和异氟醚麻醉时脑电图爆发抑制比（BSR）（从 26.6（10.2）%到 44.3（6.8）%；P=0.0027）。表达 orexin-1 受体或 orexin-2 受体的多巴胺能神经元的百分比分别为 73.4（5.0）%和 74.4（62.4）%。光遗传学激活 VTA 中的 orexin 能投射减少了 BSR（从 40.5（2.7）%到 22.4（11.8）%；P=0.0019）并促进了苏醒（915（89）到 685（68）s；P=0.0026），而光抑制则延长了清醒时间（从 941（92）到 1279（250）s；P=0.011）。VTA 中的多巴胺能神经元在浴用 orexin-A 后表现出更高的放电频率（对照的 387（78）%，P=0.005）。
orexin 通过激活 VTA 中的多巴胺能神经元促进异氟醚麻醉后的苏醒。
