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Propofol Anesthesia Affects GABA_A Receptor In Nucleus Basalis Mediating Frontal Cortex Rhythms

Posted on:2018-02-28Degree:MasterType:Thesis
Country:ChinaCandidate:F ShiFull Text:PDF
GTID:2334330536958383Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Objective: The nucleus basalis are influenced by multiple afferents from the hypothalamus and brainstem,meanwhile project to the cerebral cortex,consistent with the notion that the NB serves as a major relay between the reticular activating system and the cortex.Propofol is commonly used in clinical as a classical intravenous anesthetic and the gamma-aminobutyric-acid-type-A(GABA_A)receptor is recognized as an important target of propofol anesthesia.However the contribution of NB neurons and GABA_A receptor in NB to propofol anesthesia is still not well understood.In the present study,we investigate if NB lesion and intracerebral injection of muscimol and gabazine into the NB could influence the induction and arousal of propofol anesthesia,through recording the changes of both righting reflex and neural activities in frontal cortex.Methods: Fifty healthy male SD rats(250-350g)were used in this study.This experiment was divided into two parts,the first part was NB lesion experiment and the second part was microinjection experiment.Part 1: Twenty male SD rats were randomly divided into control group and NB-lesion group.Rats received phosphate buffer or ibotenic acid(10 μg/μl,1μl)into the unilateral of NB.Two weeks later,measured 50% effective doses(ED50)of propofol by up-down intravenous administration method.Afterwards,rats were intravenous injected with propofol(50mg/kg/h)to test the time of loss of righting reflex(LORR).Ultimately,rats received a bolus of propofol(12mg/kg)to measure the time of return of righting reflex(RORR)and recorded the electroencephalogram activity of frontal cortex under propofol anesthesia(50mg/kg/h).Part 2: Thirty male SD rats were randomly divided into saline group(0.9%,1μl),muscimol group(0.5μg/μl,1μl)and gabazine group(0.2μg/μl,1μl).Rats were microinjected of saline,muscimol and gabazine into NB respectively in three groups and the microinjection speed was 0.25μl/min.First,rats were intravenous injected with propofol(50mg/kg/h)to test the time of LORR after microinjection.Then,rats received a bolus of propofol(12mg/kg)to measure the time of RORR pre-microinjection.Ultimately,EEG in frontal cortex was recorded under propofol anesthesia(50mg/kg/h).Results:Part 1: The numbers of NB neurons were markedly reduced ~44% in the IBA-treated rats compared with control group(P < 0.05).The dose-response curve of propofol shifted to left slightly in lesion group(P > 0.05).Lesion group and control group showed similar onset time to LORR(P > 0.05).However,NB lesion significantly prolonged the time of RORR(P < 0.05)and increased delta power of frontal cortex under propofol anesthesia(P< 0.05).Part 2: For muscimol group,it prolonged the time of RORR(P < 0.05),increased EEG delta power(P < 0.05)and decreased gamma power(P < 0.05),but had no significant influence on the time of LORR(P >0.05)and ED50(P > 0.05)compared with saline group.For gabazine group,it accelerated propofol anesthesia emergency(P < 0.05)and decreased EEG delta power(P < 0.05),but does not obvious change propofol induction time(P >0.05)and ED50(P > 0.05)compared with saline group.Conclusion:(1)These unilateral NB lesion significantly increase the recovery time for propofol anesthesia and increase the delta power in frontal cortex,show that NB region might be involved in the emergence from propofol anesthesia.(2)Propofol anesthesia affecting GABA_A receptor in nucleus basalis seems to play a crucial role in mediating anesthesia recovery process and frontal cortex activity.
Keywords/Search Tags:nucleus basalis, propofol, righting reflex, EEG, GABA_A
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