丙泊酚与gaba受体
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© 2009 Elsevier Ireland Ltd. All rights reserved.
As a rapid- and short-acting intravenous anesthetic agent, propofol has been widely used in induction of general anesthesia for many years [12,14,18]. Anesthetic doses of propofol can stably induce general anesthesia-related effects such as loss of consciousness, abolition of reflex movements and loss of learning and memory abilities. However, the mechanism underlying its anesthetic effects on human beings is not yet fully understood.
Magnetic resonance spectroscopy (MRS) has become a noninvasive technique that can determine metabolic and biochemical parameters in vivo [4]. MRS is based on the principle that chemical shift is present in the resonance frequency of atomic nuclei in different electrochemical environments. After the raw chemical shift data are subjected to the Fourier transform, a conventional spectrum in which signal amplitude is plotted as a function of frequency can be obtained. As the precise resonance frequency of a particular atomic nucleus is constant in a particular molecular environment, different metabolites can be identified and distinguished from others by determining the difference in the resonant frequency. Moreover, the concentration of a substance can be calculated by determining the signal intensity at a particuபைடு நூலகம்ar frequency. As the area under a peak at a particular frequency is directly proportional to the resonance number of an atomic nucleus at a
Neuroscience Letters 467 (2009) 247–251
Contents lists available at ScienceDirect
Neuroscience Letters
journal homepage: www.elsevier.com/locate/neulet
Effect of propofol on the levels of neurotransmitters in normal human brain: A magnetic resonance spectroscopy study
Hui Zhang a,1, Wei Wang b,1, Wei Gao a, Yali Ge c, Jinsong Zhang c, Shengxi Wu b, Lixian Xu a,∗
a Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi’an 710032, China b Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, China c Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
Animal experiments have demonstrated that general anesthetics including propofol function mainly by affecting synaptic transmission, by altering neurotransmitter release presynapticly and by modulating their responses to neurotransmitters postsynapticly [1,17,19,20,23]. It has been confirmed that general anesthetics could modulate the release of neurotransmitters such as N-acetyl aspartate (NAA), glutamate (GLU), ␥-aminobutyric acid (GABA) and acetylcholine (Ach) in the central nervous system (CNS). The anesthetic effects on GABAergic and glutamatergic neu-
∗ Corresponding author. Tel.: +86 29 84776115; fax: +86 29 84776115. E-mail address: kqmzk@126.com (L. Xu).
1 These authors contributed equally to this work.
article info
Article history: Received 31 August 2009 Received in revised form 15 September 2009 Accepted 16 October 2009
Keywords: Propofol Magnetic resonance spectroscopy Neurotransmitters Anesthesia Human brain
0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2009.10.052
rotransmission occur at clinically relevant concentrations in the CNS, consistent with substantial involvement of these systems in the mechanisms of anesthesia [3,17,21]. However, most of the results were obtained from animals or in vitro studies with observations on brain slices. There is still a lack of direct clinical evidence because there was no proper research method.
abstract
Though widely used in anesthesia for many years, the mechanism underlying propofol anesthesia on human is not clear. Animal studies have already demonstrated that propofol functioned mainly by affecting neurotransmitters release. In our study, 10 healthy volunteers ranging from 20 to 40 years old were enrolled. With the help of target-controlled infusion pump, propofol was delivered intravenously. The target-controlled concentration (TCC) of propofol was gradually elevated from 0.5 to 3.0 g/ml (for 6 steps with an increment of 0.5 g/ml). During each step the Observer’s Assessment of Alertness/Sedation Scale (OAA/S) was performed to evaluate asleep to awake/alert status. Magnetic resonance spectroscopy (MRS) was performed to evaluate neurotransmitters (choline compounds (Cho), creatine (Cr), glutamate (GLU), ␥-aminobutyric acid (GABA) and N-acetyl aspartate (NAA)) changes in brains following propofol anesthesia. OAA/S scoring showed that when the TCCs of propofol were 0, 1.5 and 3.0 g/ml, the volunteers were in awake, sedative and unconscious, respectively. Significantly down-regulated Cho and GLU, but up-regulated GABA was observed in unconscious state in all the detected regions. NAA was decreased in unconscious status only in the hippocampus and thalamus. There was no obvious change in Cr levels in any statuses or brain regions. Our results indicate that propofol has an impact on the levels of neurotransmitters such as NAA, GLU, GABA and Cho in normal human brain. During propofol anesthesia, enhancement of inhibition or suppression of excitation may each play key roles in different brain regions.
As a rapid- and short-acting intravenous anesthetic agent, propofol has been widely used in induction of general anesthesia for many years [12,14,18]. Anesthetic doses of propofol can stably induce general anesthesia-related effects such as loss of consciousness, abolition of reflex movements and loss of learning and memory abilities. However, the mechanism underlying its anesthetic effects on human beings is not yet fully understood.
Magnetic resonance spectroscopy (MRS) has become a noninvasive technique that can determine metabolic and biochemical parameters in vivo [4]. MRS is based on the principle that chemical shift is present in the resonance frequency of atomic nuclei in different electrochemical environments. After the raw chemical shift data are subjected to the Fourier transform, a conventional spectrum in which signal amplitude is plotted as a function of frequency can be obtained. As the precise resonance frequency of a particular atomic nucleus is constant in a particular molecular environment, different metabolites can be identified and distinguished from others by determining the difference in the resonant frequency. Moreover, the concentration of a substance can be calculated by determining the signal intensity at a particuபைடு நூலகம்ar frequency. As the area under a peak at a particular frequency is directly proportional to the resonance number of an atomic nucleus at a
Neuroscience Letters 467 (2009) 247–251
Contents lists available at ScienceDirect
Neuroscience Letters
journal homepage: www.elsevier.com/locate/neulet
Effect of propofol on the levels of neurotransmitters in normal human brain: A magnetic resonance spectroscopy study
Hui Zhang a,1, Wei Wang b,1, Wei Gao a, Yali Ge c, Jinsong Zhang c, Shengxi Wu b, Lixian Xu a,∗
a Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi’an 710032, China b Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, China c Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
Animal experiments have demonstrated that general anesthetics including propofol function mainly by affecting synaptic transmission, by altering neurotransmitter release presynapticly and by modulating their responses to neurotransmitters postsynapticly [1,17,19,20,23]. It has been confirmed that general anesthetics could modulate the release of neurotransmitters such as N-acetyl aspartate (NAA), glutamate (GLU), ␥-aminobutyric acid (GABA) and acetylcholine (Ach) in the central nervous system (CNS). The anesthetic effects on GABAergic and glutamatergic neu-
∗ Corresponding author. Tel.: +86 29 84776115; fax: +86 29 84776115. E-mail address: kqmzk@126.com (L. Xu).
1 These authors contributed equally to this work.
article info
Article history: Received 31 August 2009 Received in revised form 15 September 2009 Accepted 16 October 2009
Keywords: Propofol Magnetic resonance spectroscopy Neurotransmitters Anesthesia Human brain
0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2009.10.052
rotransmission occur at clinically relevant concentrations in the CNS, consistent with substantial involvement of these systems in the mechanisms of anesthesia [3,17,21]. However, most of the results were obtained from animals or in vitro studies with observations on brain slices. There is still a lack of direct clinical evidence because there was no proper research method.
abstract
Though widely used in anesthesia for many years, the mechanism underlying propofol anesthesia on human is not clear. Animal studies have already demonstrated that propofol functioned mainly by affecting neurotransmitters release. In our study, 10 healthy volunteers ranging from 20 to 40 years old were enrolled. With the help of target-controlled infusion pump, propofol was delivered intravenously. The target-controlled concentration (TCC) of propofol was gradually elevated from 0.5 to 3.0 g/ml (for 6 steps with an increment of 0.5 g/ml). During each step the Observer’s Assessment of Alertness/Sedation Scale (OAA/S) was performed to evaluate asleep to awake/alert status. Magnetic resonance spectroscopy (MRS) was performed to evaluate neurotransmitters (choline compounds (Cho), creatine (Cr), glutamate (GLU), ␥-aminobutyric acid (GABA) and N-acetyl aspartate (NAA)) changes in brains following propofol anesthesia. OAA/S scoring showed that when the TCCs of propofol were 0, 1.5 and 3.0 g/ml, the volunteers were in awake, sedative and unconscious, respectively. Significantly down-regulated Cho and GLU, but up-regulated GABA was observed in unconscious state in all the detected regions. NAA was decreased in unconscious status only in the hippocampus and thalamus. There was no obvious change in Cr levels in any statuses or brain regions. Our results indicate that propofol has an impact on the levels of neurotransmitters such as NAA, GLU, GABA and Cho in normal human brain. During propofol anesthesia, enhancement of inhibition or suppression of excitation may each play key roles in different brain regions.