Biomaterial Database

Medial septal cholinergic neurons modulate isoflurane anesthesia. 2014

Siew Kian Tai, and Jingyi Ma, and L Stan Leung

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.

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

UI	MeSH Term	Description	Entries
D007530	Isoflurane	A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.
D007649	Ketamine	A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.	2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D008297	Male		Males
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010275	Parasympathetic Nervous System	The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system.	Nervous System, Parasympathetic,Nervous Systems, Parasympathetic,Parasympathetic Nervous Systems,System, Parasympathetic Nervous,Systems, Parasympathetic Nervous
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004567	Electrodes, Implanted	Surgically placed electric conductors through which ELECTRIC STIMULATION is delivered to or electrical activity is recorded from a specific point inside the body.	Implantable Electrodes,Implantable Stimulation Electrodes,Implanted Electrodes,Implanted Stimulation Electrodes,Electrode, Implantable,Electrode, Implantable Stimulation,Electrode, Implanted,Electrode, Implanted Stimulation,Electrodes, Implantable,Electrodes, Implantable Stimulation,Electrodes, Implanted Stimulation,Implantable Electrode,Implantable Stimulation Electrode,Implanted Electrode,Implanted Stimulation Electrode,Stimulation Electrode, Implantable,Stimulation Electrode, Implanted,Stimulation Electrodes, Implantable,Stimulation Electrodes, Implanted
D004569	Electroencephalography	Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain.	EEG,Electroencephalogram,Electroencephalograms
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000076985	Saporins	Type 1 ribosome-inactivating proteins derived from SAPONARIA OFFICINALIS that function through endohydrolysis of the N-glycosidic bond at single ADENOSINE residues of 28S RIBOSOMAL RNA. They are used as IMMUNOTOXINS.	RIP Ribosome-Inactivating Protein,Ribosome-Inactivating Protein,SAP5 Protein,SAP6 Protein,Saporin,Saporin 5 Protein,Saporin 6 Protein,Saporin Protein,Saporin-S9 Protein,Protein, RIP Ribosome-Inactivating,RIP Ribosome Inactivating Protein,Ribosome Inactivating Protein,Ribosome-Inactivating Protein, RIP,Saporin S9 Protein