丘脑网状核在睡眠中的作用

背景 睡眠是脑的重要功能活动之一,是人类生存的必要条件.而γ-氡基丁酸(γ-aminobutyric acid,GABA)是中枢神经系统广泛分布的一种抑制性神经递质,睡眠以及全身麻醉的产生均与GABA存在密切的关系. 目的 综述丘脑皮质系统中富含GABA神经元的丘脑网状核(thalamic reticular nucleus,TRN)在睡眠中的作用. 内容 丘脑网状核可能会通过其抑制性闸门作用调节睡眠. 趋向 TRN及其参与的丘脑-皮质环路在睡眠中的相关生理机制为睡眠及相关全身麻醉研究提供了一新靶点.     

在麻醉致意识消失期间丙泊酚和乙托咪酯对大脑皮质、丘脑及网状结构神经元的抑制作用

背景麻醉致意识消失的作用位点仍不清楚。可能的位点包括大脑皮质、丘脑和网状结构。我们研究了丙泊酚和乙托咪酯对正常动物皮质、丘脑及网状结构神经元功能的影响。方法对5只猫在麻醉状态下放置记录套管和脑电波螺丝钉电极。经过5天恢复期之后,每周重复检查3～4次。在给予丙泊酚或乙托咪酯注射之前、注射期间和注射之后记录大脑皮质（7、18和19区）、丘脑（腹后外侧核、腹后内侧核和内侧膝状体）及网状结构（中脑网状核群和中央被盖区）单个神经元的电活动。皮质神经元的动作电位按脉冲神经元和快速放电神经元分别进行分析。结果丙泊酚和乙托咪酯使皮质神经元自发放电频率降低37％-41％。两种麻醉剂对脉冲神经元和快速放电神经元的作用相似。丙泊酚和乙托咪酯亦使丘脑和网状结构神经元放电频率减低30％～49％。麻醉剂输注期间皮质、丘脑及网状结构脑电图表现相似,均从低幅高频快波变为高幅低频慢波;功率峰值发生于丙泊酚输注期间,频率为12～13Hz。乙托咪酯麻醉期间有2个大的峰值：一个频率为12—14Hz,另一个为7～8Hz。检测过程中猫处于深度镇静状态,瞬目反射和动须反射消失而伤害性刺激}】起的退缩反应保存。结论数据资料显示丙泊酚和乙托咪酯抑制大脑皮质、丘脑及网状结构神经元的作用相似。尽管麻醉剂对神经元电活动的抑制作用可能是麻醉剂致意识消失的潜在机制,但仍需进一步研究阐明上述位点的麻醉剂效应如何相互影响而终致意识消失。     

丙泊酚对大鼠不同脑区氨基酸类递质的影响

目的 观察丙泊酚麻醉下大鼠不同脑区氨基酸类神经递质水平的变化,探讨丙泊酚麻醉中枢作用的可能机制.方法 12只大鼠随机分为丙泊酚组和对照组,按照不同的坐标预埋微透析探针,分别持续静注丙泊酚和生理盐水60 min.收集微透析液样品,用高效液相色谱-电化学法测定氨基酸类递质含量.结果 实验大鼠各脑区谷氨酸(Glu)、天冬氨酸(Asp)、γ-氨基丁酸(GABA)、甘氨酸(Gly)的分布存在较大差异,丙泊酚组皮质、海马、丘脑Glu、Asp含量较对照组显著下降(P<0.01),纹状体区也下降明显(P<0.05);而皮质、海马、丘脑、纹状体GABA、Gly含量则明显升高(P<0.01).结论 丙泊酚对大鼠中枢神经系统氨基酸类递质有不同程度的影响,抑制兴奋性氨基酸突触传递而增强抑制性氨幕酸突触传递可能是其中枢作用的机制之一.     

脑fMRI观察电针神门及三阴交穴治疗失眠机制

目的利用fMRI技术探讨电针神门、三阴交穴治疗失眠的机制。方法对7名失眠患者（失眠组）及6名健康志愿者（正常对照组）分别在无任何刺激状态下行静息扫描、电针刺激双侧神门和三阴交穴下行BOLD-fMRI扫描,观察两组受试者的激活脑功能区。采用SPM基本模式中的单样本t检验进行统计分析。结果两组受试者均可见脑岛（BA13）明显激活。但在失眠组,右侧丘脑腹前核、右侧壳核、左内侧苍白球、左侧中央前回（BA9）、双侧尾状核头部被特异性地激活。结论电针神门、三阴交穴治疗失眠的机制可能是电针刺激激活了丘脑腹前核、尾状核、壳核、内侧苍白球、丘脑网状核以及其他睡眠中枢,整合传入和传出的信息,调节睡眠;并可通过不同的通路调畅情志,舒缓压力,达到助眠作用。     

臂旁核神经通路在全身麻醉致意识改变中作用的研究进展

全身麻醉药(以下简称全麻药)的主要药理效应包括:可逆性的意识消失、镇痛、遗忘以及肌松作用, 其中意识消失是其最具特征性的表现。迄今为止, 全麻药通过何种机制介导意识消失与恢复仍不明确。近年来, 多项研究从神经网络调控理论出发以期阐明全身麻醉的调控靶点, 发现蓝斑核[1]、伏隔核[2]、中缝背核[3]、外侧下丘脑[4]等核团均参与全身麻醉的过程, 运用光遗传学、化学遗传学等方法调控核团内特定类型的神经元会影响麻醉诱导时间和麻醉苏醒时间, 并伴有皮层脑电的同步变化。然而, 全身麻醉下通过兴奋或抑制某单个核团, 并不能呈现完整的意识变化, 提示全身麻醉致意识改变可能是神经通路共同参与调控的结果。因此, 探索全麻药对不同神经通路的具体作用可能有助于解开全身麻醉药致意识改变的作用机制。     

缰核参与感觉及情感调控的研究进展

背景 缰核是一个骑跨在第三脑室上的双侧性的小结构,位于背侧丘脑中后部,分为内侧缰核(medial habenula,MHb)和外侧缰核(lateral habenula,LHb).近年来研究发现缰核参与对疼痛的行为反应、奖赏-厌恶、抑郁、成瘾及母性行为等多种生理及病理过程的调节. 目的 阐明缰核在感觉情感调控中的重要作用,为相关临床研究提供新的思路. 内容 综述缰核在感觉及情感的调控中发挥作用的机制和环路. 趋向 随着研究的深入,缰核未来可能成为临床多种感觉情感疾病的治疗靶点.     

丙泊酚人脑中枢作用部位的功能磁共振成像分析

目的应用功能磁共振成像技术（fMRI）研究丙泊酚对健康志愿者脑不同部位功能变化的影响，探索丙泊酚在脑内的可能作用部位。方法采用丙泊酚静脉麻醉的刺激程序：清醒-镇静-意识消失-苏醒的动态过程，丙泊酚麻醉按1．5mg／kg通过恒速泵静脉注射，注射时间均为90s。采用1．5T Philips Gyroscan磁共振系统，运用单次激发平面回波序列（EPI）扫描序列进行脑功能血氧水平依赖（BOI．D）法成像并应用Functool软件进行功能分析。结果丙泊酚麻醉可抑制下丘脑磁共振信号，r值为0．75，信号变化强度为（20．2±11．6）％；可降低额叶信号，r值为0．71，信号降低强度为（37．5±16．7）0A；颞叶信号也受到抑制，r值为0．72，信号变化强度为（33．8±10．4）％。三个部位信号的抑制呈爆发性，变化过程同步，信号降低强度额叶〉颞叶〉下丘脑，但三者间差异无统计学意义。丘脑部位信号也明显降低，r值为0．60，信号变化强度为（3．9±1．6）％，与额叶、颞叶、下丘脑相比，差异均有统计学意义（P〈0．05）。结论丙泊酚麻醉首先抑制下丘脑、额叶、颞叶区域，随后丘脑区域受到抑制，这些区域可能是丙泊酚麻醉作用的靶位。     

全身麻醉药在脊髓内的作用机制

脊髓是全身麻醉药抑制伤害性刺激体动反应和抗伤害效应的重要作用部位,含有不同配体门控离子受体等多个可能介导麻醉效应的靶点.不同药物在脊髓内经各自特异靶点通过多种分子机制发挥作用.现就全身麻醉药制动和镇痛效应在脊髓内的作用位点和分子机制作一综述.     

PET分析丙泊酚对人脑葡萄糖能量代谢的影响

目的　应用正电子发射计算机体层显像(PET)技术,观察丙泊酚对人脑不同区域内葡萄糖能量代谢(CMGlu)的影响,探讨丙泊酚在人脑可能的作用部位。方法　健康志愿者 7 名,每位志愿者分别在清醒、丙泊酚 1 .5μg/ml(镇静)和 3 0μg/ml(意识消失)靶浓度状态下注射18氟脱氧葡萄糖(18F -FDG)显像剂,平衡后进行PET扫描。以清醒状态作为对照,通过靶控输注(TCI)丙泊酚使志愿者达到镇静和意识消失状态。结果　(1)与清醒状态比较,镇静状态下脑电双频指数(BIS)明显降低(P<0. 05),平均动脉压(MAP)、呼吸频率(RR)和心率(HR)等指标无显著性改变;而意识消失状态下,MAP、BIS降低,呼吸抑制,呼气末二氧化碳分压( PET CO2 )升高,均有显著性差异(P<0. 05)。(2)与清醒状态比较,镇静状态下全脑的CMGlu下降(18. 0±4. 0)%。CMGlu的下降在大脑皮质最为明显(P<0. 05)。CMGlu在丘脑、小脑、海马和桥脑等区域也有不同程度的降低,但与清醒状态比较,无显著性差异。意识消失状态下,全脑 CMGlu 与清醒状态比较显著下降了(34. 1±7 .0)%(P<0 .05),在丘脑、大脑皮质、小脑和海马等区域 CMGlu明显低于清醒状态(P<0 .05),其中丘脑降幅最大为(51. 5±5 .0)%。结论　丙泊酚麻醉可明显降低全脑能量代谢,低剂量的丙泊酚首先影响皮层区的能量代谢,     

上行网状激活系统与睡眠-觉醒和全身麻醉的研究进展

全身麻醉如何导致意识的可逆性消失是探究全身麻醉机制的核心内容。近年来，经过脂质学说、蛋白学说和离子通道学说三个阶段后，全身麻醉与神经通路之间的联系已成为研究热点。目前的研究表明，全身麻醉状态与生理性睡眠存在一定相似之处。上行网状激活系统包含多种神经元及核团，通过投射及释放相关神经递质，促进并维持生物的觉醒，而全身麻醉药也共享了其中的某些通路及递质。本文通过综述近年上行网状激活系统中关键核团在睡眠-觉醒过程中作用机制的研究进展，探讨网状激活系统与睡眠-觉醒、全身麻醉的关系，为阐明全身麻醉的药物作用机制、探寻临床治疗睡眠障碍新

方法 提供参考。     

Propofol, more than halothane, depresses electroencephalographic activation resulting from electrical stimulation in reticular formation

BACKGROUND: Halothane and propofol depress the central nervous system, and this is partly manifested by a decrease in electroencephalographic (EEG) activity. Little work has been performed to determine the differences between these anesthetics with regard to their effects on evoked EEG activity. We examined the effects of halothane and propofol on EEG responses to electrical stimulation of the reticular formation. METHODS: Rats (n= 12) were anesthetized with either halothane or propofol, and EEG responses were recorded before and after electrical stimulation of the reticular formation. Two anesthetic concentrations were used (0.8 and 1.2 times the amount needed to prevent gross, purposeful movement in response to supramaximal noxious stimulation), and both anesthetics were studied in each rat using a cross-over design. RESULTS: Electrical stimulation in the reticular formation increased the spectral edge (SEF) and median edge (MEF) frequencies by approximately 1-2 Hz during halothane anesthesia at low and high concentrations. During propofol anesthesia, MEF increased at the low propofol infusion rate, but SEF was unaffected. At the high propofol infusion rate, SEF and MEF decreased following electrical stimulation in the reticular formation. CONCLUSIONS: At immobilizing concentrations, propofol produces a larger decrease than halothane in EEG responses to reticular formation stimulation, consistent with propofol having a more profound depressant effect on cortical and subcortical structures.     

异丙酚不同麻醉深度下兔脑5-羟色胺代谢水平的变化

目的 研究异丙酚不同麻醉深度下兔脑5-羟色胺(5-HT)代谢水平的改变。方法 选日本大耳兔40只，年龄8月-2岁，体重2-3kg，雌雄不拘。10只兔颈外静脉连接Graseby3500注射泵进行靶控输注(TCI)。应用异丙酚TCI系统，确定不同麻醉深度下所需的异丙酚靶控血药浓度。以咀嚼反射消失作为浅麻醉标志，以夹尾后无体动反应为深麻醉。30只日本大耳兔随机分为三组：对照组、浅麻醉组和深麻醉组(各10只)。1h后断头处死，迅速冰上分离大脑皮层、海马和丘脑并匀浆，测定5-HT及5-羟吲哚醋酸(5-HIAA)的含量。观察异丙酚不同麻醉深度下兔大脑皮层、海马和丘脑5-HT代谢水平的改变。结果 大脑皮层5-HT水平在麻醉后显著性增加，海马5-HT水平和丘脑5-HM水平随麻醉浓度的增加而显著性降低。结论 异丙酚显著性增加大脑皮层和丘脑的5-HT活性，降低海马区5-HT的活性，表明5-HT在异丙酚的麻醉作用机制中发挥一定的作用。     

The effects of propofol anesthesia on local cerebral glucose utilization in the rat

The autoradiographic 14C-2-deoxy-D-glucose method was used to determine local cerebral glucose utilization (LCGU) during propofol anesthesia and recovery in 52 regions of the rat brain. Control rats intravenously received 5 ml.kg-1.h-1 of the egg-oil-glycerol emulsion that constitutes the vehicle for propofol. Anesthetized animals received an iv bolus of propofol (20 mg/kg) followed by continuous infusion of the anesthetic at 12.5, 25, or 50 mg.kg-1.h-1 for 1 h prior to injection of 14C-2-deoxy-D-glucose and for the following 45 min. In addition, a fifth group of animals were studied immediately after awakening from a 20 mg/kg bolus of propofol as indicated by the first reappearance of head lift. All rats were spontaneously breathing room air throughout the experimental procedure. The general pattern of the cerebral metabolic response to propofol anesthesia was a dose-related, widespread depression of LCGU. At the three infusion rates of propofol tested, overall mean LCGU was reduced by 33%, 49%, and 55%, respectively, and significant decreases were observed in 60%, 85%, and 90% of the regions assayed. These effects were rapidly reversible, since in the recovery group, LCGU returned to near control values in the majority of the brain areas. Although all of the anatomofunctional systems (sensorimotor, extrapyramidal, limbic, and reticular) were involved, forebrain structures showed a greater sensitivity to the depressant action of propofol than did hindbrain regions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of 3 different anesthetic techniques on 24-hour recovery after otologic surgical procedures.

Intravenous propofol anesthesia is better than inhalational anesthesia for otologic surgery, but cost and intraoperative movement make this technique prohibitive. This study compares a propofol sandwich anesthetic with a total propofol or inhalational anesthetic for otologic surgery to determine which produces the best perioperative conditions and least expense. One hundred twenty patients undergoing ear surgery were randomly chosen to receive an anesthetic with either isoflurane (INHAL), total propofol (TPROP), or propofol used in conjunction with isoflurane (PSAND). Postoperative wakeup and the incidence and severity of nausea, vomiting, and pain were compared among groups. Antiemetic administration and discharge times from recovery and the hospital were also compared. The groups were similar, but anesthesia times were longer in the INHAL group. Emergence from anesthesia after PSAND or TPROP was more rapid than after INHAL. Recovery during the next 24 hours was associated with less nausea and vomiting with PSAND than with INHAL. The cost of the PSAND anesthetic was similar to that of INHAL, and both were less than TPROP. PSAND anesthesia may be similar to TPROP and better than INHAL for otologic procedures. PSAND was less expensive than TPROP and produced a similar recovery profile and antiemetic effect in the 24-hour period after surgery.     

Predictors of hypotension after induction of general anesthesia

Hypotension after induction of general anesthesia is a common event. In the current investigation, we sought to identify the predictors of clinically significant hypotension after the induction of general anesthesia. Computerized anesthesia records of 4096 patients undergoing general anesthesia were queried for arterial blood pressure (BP), demographic information, preoperative drug history, and anesthetic induction regimen. The median BP was determined preinduction and for 0-5 and 5-10 min postinduction of anesthesia. Hypotension was defined as either: mean arterial blood pressure (MAP) decrease of >40% and MAP <70 mm Hg or MAP <60 mm Hg. Overall, 9% of patients experienced severe hypotension 0-10 min postinduction of general anesthesia. Hypotension was more prevalent in the second half of the 0-10 min interval after anesthetic induction (P < 0.001). In 2406 patients with retrievable outcome data, prolonged postoperative stay and/or death was more common in patients with versus those without postinduction hypotension (13.3% and 8.6%, respectively, multivariate P < 0.02). Statistically significant multivariate predictors of hypotension 0-10 min after anesthetic induction included: ASA III-V, baseline MAP <70 mm Hg, age > or =50 yr, the use of propofol for induction of anesthesia, and increasing induction dosage of fentanyl. Smaller doses of propofol, etomidate, and thiopental were not associated with less hypotension. To avoid severe hypotension, alternatives to propofol anesthetic induction (e.g., etomidate) should be considered in patients older than 50 yr of age with ASA physical status > or =3. We conclude that it is advisable to avoid propofol induction in patients who present with baseline MAP <70 mm Hg.     

Tumor necrosis factor-alpha reduces ketamine- and propofol-induced anesthesia time in rats

Tumor necrosis factor-alpha (TNFalpha) is a crucial neuromodulator in the brain. TNFalpha is involved in many physiological events including pain response and sleep. However, the interactions between TNFalpha and anesthetics have not been elucidated yet. In the present study, we investigated the effects of four intracerebroventricular (ICV) doses (1, 10, and 100 pg, and 1 ng) and two intraperitoneal (IP) doses (10 and 100 ng) of TNFalpha on anesthesia time of ketamine (100 mg/kg IP) and propofol (80 mg/kg IP) in rats. All ICV doses of TNFalpha reduced anesthesia time of ketamine and propofol compared with the saline ICV group (ketamine control group, 45.4 +/- 6.5 min; propofol control group, 43.5 +/- 11.0 min). The maximum effect was obtained after the ICV injection of 10 pg of TNFalpha (76% and 54% of ketamine and propofol control groups, respectively). Anesthesia time of ketamine or propofol was also decreased by IP injection of TNFalpha in a dose-dependent manner. Injection of 100 ng of TNFalpha IP reduced anesthesia time of ketamine and propofol by 67% and 64% of each control group, respectively. These data show that TNFalpha can modulate the anesthesia time of IV anesthetics, suggesting that anesthetic requirements might be altered in the presence of cerebral or systemic inflammation. IMPLICATIONS: Tumor necrosis factor alpha (TNFalpha) regulates many physiological events in the brain. We investigated the effects of TNFalpha on anesthesia time in rats. Both central and peripheral administration of TNFalpha decreased anesthesia time induced by ketamine and propofol.     

A randomized trial of propofol consumption and recovery profile with BIS‐guided anesthesia compared to standard practice in children

Aim: To evaluate the impact of bispectral index (BIS) monitoring on the consumption of propofol and recovery from anesthesia compared to the standard clinical practice in children. Background: Titrating propofol administration using BIS reduces its requirement and shortens the recovery from anesthesia in adults. However, there is still mixed evidence for utility of anesthesia depth monitors in reducing anesthesia requirement in children. Methods/Materials: A prospective randomized study was conducted in 50 ASA I children of 2–12 years, randomly assigned into standard practice (SP) or BIS group. After induction with propofol, anesthesia was maintained with 150 μg·kg^?1·min^?1 propofol infusion. The propofol infusion rate was altered by 20 μg·kg^?1·min^?1 to maintain the systolic blood pressure within 20% of the baseline (SP group) or BIS value between 45 and 60 (BIS group). The rate of propofol infusion was reduced by 50% about 15 min before the end of surgery. The amount of propofol used and the times from stopping the propofol infusion to eye opening, extubation, response to commands and attaining Steward score of 6 were recorded. Results: There was no evidence of a difference in the mean propofol consumption in the two groups (BIS 232.6 ± 136.7 mg, SP 250.8 ± 118.2 mg). The intraoperative hemodynamics and BIS values were similar in the two groups. There was no evidence for a difference between groups in the mean times from termination of anesthetic to eye opening, extubation, response to commands and to achieve a Steward Recovery score of 6. Conclusions: Our study showed no benefit of BIS‐guided propofol administration on anesthetic consumption or recovery compared to standard anesthetic practice.     

Positron Emission Tomography Study of Regional Cerebral Metabolism in Humans during Isoflurane Anesthesia

Background: Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on human cerebral glucose metabolism using positron emission tomography (PET).

Methods: Five volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/- SD; expired = 0.5 +/- 0.1%). Scans were obtained with a GE2048 scanner (4.5-mm resolution-FWHM) using the18 fluorodeoxyglucose technique.

Results: Awake whole-brain glucose metabolism averaged 6.9 +/- 1.5 mg [center dot] 100 g sup -1 [center dot] min sup -1 (means +/- SD). Isoflurane reduced whole-brain metabolism 46 +/- 11% to 3.6 +/- 0.3 mg [center dot] 100 g sup -1 [center dot] min sup -1 (P less or equal to 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region-of-interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake.     

Anesthetic properties of 4-iodopropofol: implications for mechanisms of anesthesia

BACKGROUND: Positive modulation of gamma-aminobutyric acid type A (GABAA) receptor function is recognized as an important component of the central nervous system depressant effects of many general anesthetics, including propofol. The role for GABAA receptors as an essential site in the anesthetic actions of propofol was recently challenged by a report that the propofol analog 4-iodopropofol (4-iodo-2,6-diisopropylphenol) potentiated and directly activated GABAA receptors, yet was devoid of sedative-anesthetic effects in rats after intraperitoneal injection. Given the important implications of these findings for theories of anesthesia, the authors compared the effects of 4-iodopropofol with those of propofol using established in vivo and in vitro assays of both GABAA receptor-dependent and -independent anesthetic actions. METHODS: The effects of propofol and 4-iodopropofol were analyzed on heterologously expressed recombinant human GABAA alpha1beta2gamma2 receptors, evoked population spike amplitudes in rat hippocampal slices, and glutamate release from rat cerebrocortical synaptosomes in vitro. Anesthetic potency was determined by loss of righting reflex in Xenopus laevis tadpoles, in mice after intraperitoneal injection, and in rats after intravenous injection. RESULTS: Like propofol, 4-iodopropofol enhanced GABA-induced currents in recombinant GABAA receptors, inhibited synaptic transmission in rat hippocampal slices, and inhibited sodium channel-mediated glutamate release from synaptosomes, but with reduced potency. After intraperitoneal injection, 4-iodopropofol did not produce anesthesia in mice, but it was not detected in serum or brain. However, 4-iodopropofol did produce anesthesia in tadpoles (EC50 = 2.5 +/- 0.5 microM) and in rats after intravenous injection (ED50 = 49 +/- 6.2 mg/kg). CONCLUSIONS: Propofol and 4-iodopropofol produced similar actions on several previously identified cellular and molecular targets of general anesthetic action, and both compounds induced anesthesia in tadpoles and rats. The failure of 4-iodopropofol to induce anesthesia in rodents after intraperitoneal injection is attributed to a pharmacokinetic difference from propofol rather than to major pharmacodynamic differences.