From the Department of Physiology and Pharmacology (S.K.T., J.M., L.S.L.) and Program in Neuroscience (L.S.L.), The University of Western Ontario, London, Ontario, Canada.
Anesthesiology. 2014 Feb;120(2):392-402. doi: 10.1097/ALN.0b013e3182a7cab6.
Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known.
Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by counting choline acetyltransferase-immunoreactive cells and parvalbumin-immunoreactive cells.
Rats with 192 immunoglobulin G-saporin lesion, as compared with control rats with sham lesion, showed a 85% decrease in choline acetyltransferase-immunoreactive, but not parvalbumin-immunoreactive, neurons in the medial septal area. Lesioned as compared with control rats showed increased isoflurane sensitivity, characterized by a leftward shift of the graph plotting cumulative LORR percent with isoflurane dose. However, lesioned and control rats were not different in their LORR sensitivity to ketamine. When administered with 1.375% isoflurane, LORR induction time was shorter, whereas emergence time was longer, in lesioned as compared with control rats. Hippocampal 62-100 Hz gamma power in the electroencephalogram decreased with isoflurane dose, with a decrease that was greater in lesioned (n = 5) than control rats (n = 5).
These findings suggest a role of the septal cholinergic neurons in modulating the sensitivity to isoflurane anesthesia, which affects both induction and emergence. The sensitivity of hippocampal gamma power to isoflurane appears to indicate anesthesia (LORR) sensitivity.
已知胆碱能药物可调节全身麻醉的反应。然而，选择性损伤投射到海马的隔区胆碱能神经元后，异氟醚或其他挥发性麻醉剂的敏感性尚不清楚。
雄性长耳大野鼠（Long Evans rats）的内侧隔区（medial septum）内注射 192 免疫球蛋白 G-皂素（immunoglobulin G-saporin）（n = 10），以选择性损伤胆碱能神经元，而对照、假损伤大鼠则用生理盐水（saline）（n = 12）进行注射。内侧隔区注射后 2 周，使用翻正反射（loss of righting reflex，LORR）丧失的行为终点测量异氟醚和氯胺酮的催眠特性。通过计数胆碱乙酰转移酶免疫反应性细胞（choline acetyltransferase-immunoreactive cells）和钙结合蛋白免疫反应性细胞（parvalbumin-immunoreactive cells）来评估隔区损伤。
与假损伤对照大鼠相比，接受 192 免疫球蛋白 G-皂素损伤的大鼠，内侧隔区的胆碱乙酰转移酶免疫反应性神经元减少了 85%，但钙结合蛋白免疫反应性神经元没有减少。与对照大鼠相比，损伤大鼠对异氟醚的敏感性增加，表现为随着异氟醚剂量的累积，LORR 百分比的图表向左移动。然而，损伤大鼠与对照大鼠对氯胺酮的 LORR 敏感性没有差异。当给予 1.375%的异氟醚时，与对照大鼠相比，损伤大鼠的 LORR 诱导时间更短，苏醒时间更长。在脑电图中，海马区 62-100 Hz 的γ功率随着异氟醚剂量的增加而降低，而损伤大鼠（n = 5）的降低幅度大于对照大鼠（n = 5）。
这些发现表明，隔区胆碱能神经元在调节异氟醚麻醉敏感性方面发挥作用，这会影响诱导和苏醒。海马区γ功率对异氟醚的敏感性似乎表明了麻醉（LORR）敏感性。
