L‐DOPA‐induced dyskinesia in a rat model of Parkinson's disease is associated with the fluctuational release of norepinephrine in the sensorimotor striatum

L‐3,4‐dihydroxyphenylalanine (L‐DOPA)‐induced dyskinesia (LID) is the most common complication of standard L‐DOPA therapy for Parkinson's disease experienced by most parkinsonian patients. LID is associated with disruption of dopaminergic homeostasis in basal ganglia following L‐DOPA administration. Norepinephrine (NE) is another important catecholaminergic neurotransmitter that is also believed to be involved in the pathogenesis of LID. This study compared NE release in the ipsilateral sensorimotor striatum of dyskinetic and nondyskinetic 6‐hydroxydopamine‐lesioned hemiparkinsonian rats treated chronically with L‐DOPA. After L‐DOPA injection, the time‐course curves of NE levels in the sensorimotor striatum were significantly different between dyskinetic and nondyskinetic rats. Several metabolic kinetic parameters of NE levels were also differentially expressed between the two groups. In comparison with nondyskinetic rats, the ΔC_max of NE was significantly higher in dyskinetic rats, whereas T_max and t_1/2 of NE were significantly shorter. Intrastriatal perfusion of NE into the lesioned sensorimotor striatum revealed a moderate dyskinesia in dyskinetic rats, which was similar to the dyskinetic behavior after L‐DOPA administration. The L‐DOPA‐related dyskinetic behavior was inhibited significantly by a further pretreatment of noradrenergic neurotoxin N‐?(2‐?chloroethyl)?‐?N‐?ethyl‐?2‐?bromobenzylamine or intrastriatal administration of the α₂‐adrenoceptor antagonist idazoxan, accompanied by significant changes in metabolic kinetic parameters of NE in the sensorimotor striatum. The results provide evidence to support the correlation between abnormal NE neurotransmission and the induction of LID and suggest that the aberrant change of the quantitative and temporal releasing of NE in the sensorimotor striatum might play an important role in the pathogenesis of LID. © 2014 Wiley Periodicals, Inc.     

Sevoflurane versus isoflurane--anaesthesia for lower abdominal surgery. Effects on perioperative glucose metabolism

BACKGROUND: The aim of this study was to determine the impact of sevoflurane anaesthesia on metabolic and endocrine responses to lower abdominal surgery. METHODS: A prospective randomized controlled study in 20 patients undergoing abdominal hysterectomy. Patients were randomly assigned to receive either sevoflurane (S) or isoflurane anaesthesia (I). Using a stable isotope dilution technique, endogenous glucose production (EGP) and plasma glucose clearance (GC) were determined pre- and postoperatively (6,6-2H2-glucose). Plasma concentrations of glucose, insulin, cortisol, epinephrine and norepinephrine were measured preoperatively, 5 min after induction of anaesthesia, during surgery and 2 h after the operation. RESULTS: EGP increased in both groups with no intergroup differences (preop. S 12.2 +/- 1.6, I 12.4 +/- 1.6; postop. S 16.3 +/- 1.9*, I 19.0 +/- 3.1* micromol kg(-1) min(-1), all values are means +/- SD, *P < 0.05 vs. preop.). Plasma glucose concentration increased and GC decreased in both groups. There were no differences between groups. (Glucose conc. mmol l(-1) preop.: S 4.1 +/- 0.3, I 3.9 +/- 0.5; 5 AI S 5.1 +/- 0.6*, I 5.1 +/- 1.0*, postop. S 7.0 +/- 1.0*, I 7.1 +/- 1.4*; * = P < 0.05 vs. preop.; GC ml kg(-1)min(-1) preop. S 3.0 +/- 0.4, I 3.2 +/- 0.4; postop. S 2.4 +/- 0.3*, I 2.7 +/- 0.3*; *=P < 0.05 vs. preop.) Insulin plasma concentrations were unchanged. Cortisol plasma concentrations increased intra- and postoperatively with no changes between the groups. Norepinephrine plasma concentration increased in the S group after induction of anaesthesia. I group norepinephrine was increased 2 h after operation and showed no intergroup differences. CONCLUSION: Sevoflurane, as well as isoflurane, does not prevent the metabolic endocrine responses to surgery.     

Catecholamine release during laparoscopic fundoplication with high and low doses of remifentanil

Background:   Reports on stress responses to laparoscopic surgery have been conflicting. Depth of anesthesia may influence the neuro-hormonal release, including catecholamines. Opioids depress general sympathetic activation in a dose-dependent manner. We investigated the hypothesis that remifentanil would depress the catecholamine response to pneumoperitoneum and laparoscopic surgery differently with a high dose (HD) compared with a low dose (LD).
Methods:   In a randomized, prospective study we investigated 18 ASA I–II patients undergoing laparoscopic fundoplication with an intra-abdominal pressure of 12 mmHg. The patients were randomized to receive either a LD (0.13 μg kg⁻¹.min⁻¹) or HD (0.39 μg kg⁻¹.min⁻¹) of remifentanil with a target-controlled infusion (TCI) technique. Bispectral index of EEG (BIS) was maintained at 40–55 by propofol delivered by a TCI system. Arterial catecholamines were analyzed at different times during the procedure.
Results:   Norepinephrine increased equally in both groups during pneumoperitoneum and surgical intervention. Epinephrine stayed low in the HD-group, while increasing during surgery in the LD-group.
Conclusion:   High dose of remifentanil depressed the epinephrine response to pneumoperitoneum and surgery, indicating no general activation of the sympathetic nervous system. Neither a LD nor HD of remifentanil depressed the norepinephrine response during pneumoperitoneum. This suggests a centrally independent release of norepinephrine.     

肝移植无肝期应用去甲肾上腺素和多巴胺对肾功能影响的比较研究

目的观察肝移植无肝期应用去甲肾上腺素和多巴胺对肾功能的影响。方法将50例晚期肝病患者,ASAⅢ~Ⅳ级,择期行经典OLT手术。随机分为两组,即多巴胺组(A组):25例腔静脉阻断前5min多巴胺5～10μg/(kg·min)持续微泵输注,使收缩压维持在80mmHg以上。对照组(B组)25例腔静脉阻断前5min去甲肾上腺素0.5~1.0μg/(kg·min)持续微泵输注,使收缩压维持在80mmHg以上。记录患者在腔静脉阻断时、阻断后20min、腔静脉开放时、术毕的HR,CVP,PAWP,MAP,UVP,PVR,SVR,CO等血流动力学指标以及尿素氮(BUN),肌酐(Cr)等肾脏功能指标。统计无肝期应用血管活性药的总量和各时间点的尿量。结果A组与B组比较COSVR,MAP-UVP在阻断后20min、腔静脉开放时有显著差异(P<0.05),而在其余时间点无显著差异(P>0.05)。HR,CVP,PAWP和PVR在腔静脉阻断时、阻断后20min、开放时及术闭时指标差异无显著性(P>0.05),无肝期每小时尿量A组与B组差异有显著性(P<0.05)。而A组与B组各时间点肌酐、尿素氮差异均无显著性(P>0.05)。无肝期应用的血管活性药两组比较有明显差异,A组多于B组(P<0.05)。结论肝移植无肝期应用去甲肾上腺素较多巴胺更能维持血流动力学稳定,并且对肾功能有保护作用,至少与多巴胺比较没有毒副作用。     

Wake‐promoting actions of noradrenergic α1‐ and β‐receptors within the lateral hypothalamic area

Central norepinephrine exerts potent wake‐promoting effects, in part through the actions of noradrenergic α₁‐ and β‐receptors located in the medial septal and medial preoptic areas. The lateral hypothalamic area (LHA), including the lateral hypothalamus, perifornical area and adjacent dorsomedial hypothalamus, is implicated in the regulation of arousal and receives a substantial noradrenergic innervation. To date the functional significance of this innervation is unknown. The current studies examined the degree to which noradrenergic α₁‐ and β‐receptor stimulation within the rat LHA modulates arousal. Specifically, these studies examined the wake‐promoting effects of intra‐tissue infusions (250 nL) of the α₁‐receptor agonist phenylephrine (10, 20 and 40 nmol) and the β‐receptor agonist isoproterenol (3, 10 and 30 nmol) in rats. Results show that stimulation of LHA α₁‐receptors elicits robust and dose‐dependent increases in waking. In contrast, β‐receptor stimulation within the LHA had relatively modest arousal‐promoting actions. Nonetheless, combined α₁‐ and β‐receptor stimulation elicited additive wake‐promoting effects. Arousal‐promoting hypocretin/orexin (HCRT)‐synthesising neurons are located within the LHA. Therefore, additional immunohistochemical studies examined whether α₁‐receptor‐dependent waking is associated with an activation of HCRT neurons as measured by Fos , the protein product of the immediate–early gene c‐fos. Analyses indicate that although intra‐LHA α₁‐receptor agonist infusion elicited a robust increase in Fos immunoreactivity (ir) in this region, this treatment did not activate HCRT neurons as measured by Fos‐ir. Collectively, these observations indicate that noradrenergic α₁‐receptors within the LHA promote arousal via actions that are independent of HCRT neuronal activation.     

中枢神经递质乙酰胆碱与去甲肾上腺素在肠易激综合征大鼠模型的表达

目的探讨中枢神经递质系统在肠易激综合征（IBS）发病机制中的可能作用。方法应用冰水灌胃法建立便秘型肠易激综合征（GIBS）大鼠模型，取大鼠的脊髓后角及下丘脑标本，分别应用抗乙酰胆碱酯酶（AchE）、酪氨酸羟化酶（TH）抗体进行免疫组织化学染色，应用彩色病理图像分析系统对阳性表达的面积、不透光率密度值进行半定量分析。结果大鼠IBS模型脊髓后角及下丘脑AchE表达的阳性面积、不透光率密度值均明显增高（P〈0．05），而TH表达的阳性面积、不透光率密度值与正常对照组比较无显著差异（P〉0．05）。结论中枢胆碱能神经系统可能参与了C-IBS的病理生理机制。     

自愿适量运动对脑的有益作用及其生物学机制

本文综述了在人和动物方面有关自愿适量运动有益于脑作用的研究,包括改善心理状态和认知功能、增强心理幸福感、降低老年痴呆症发生危险度和发挥抗抑郁及抗焦虑药的作用等。运动对脑的作用机制包含上游和下游两方面：上游途径主要涉及投射到海马的几种神经递质系统的功能增强,其中包括去甲肾上腺素、5-羟色胺、乙酰胆碱和γ-氨基丁酸;下游途径主要涉及脑源性神经营养因子的表达提高和神经元发生的增强;其中,激活β受体介导的去甲肾上腺素能神经的传递被认为是运动导致脑源性神经营养因子表达增强的前提,上述过程在细胞内的可能信号转导机制主要涉及G-蛋白偶联受体-促分裂原活化蛋白激酶-磷脂酰肌醇（-3）激酶等细胞信号转导通路的交互及正反馈调控。     

Noradrenergic modulation of gonadotrophin‐inhibitory hormone gene expression in the brain of Japanese quail

Gonadotrophin‐inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotrophin synthesis and release in birds and mammals. In Japanese quail, GnIH neurones express the noradrenergic receptor and receive noradrenergic innervation. Treatment with noradrenaline (NA) stimulates GnIH release from diencephalic tissue blocks in vitro. However, the effects of NA on hypothalamic GnIH gene expression have not been determined. We investigated noradrenergic regulation of GnIH gene expression in the brain of male quail using the selective noradrenergic neurotoxin N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine hydrochloride (DSP‐4). We first showed that DSP‐4 reduced the number of noradrenergic (dopamine‐β‐hydroxylase immunoreactive) cells in the locus coeruleus (LoC) and specifically lowered the NA concentration in the hypothalamus of male quail. Other monoamines, such as dopamine and serotonin, were not affected by drug treatment. DSP‐4 did not decrease the numbers of noradrenergic cells of the lateral tegmental cell group, nor the plasma NA concentration. Decreased hypothalamic NA levels after DSP‐4 treatment did not change GnIH gene expression in the brains of quail during their interaction with conspecifics. On the other hand, GnIH gene expression increased in the brains of quail socially isolated for 1 hour after DSP‐4 treatment. These results suggest that some noradrenergic neurones have inhibitory effects on GnIH gene expression of the hypothalamus in solitary quail.     

Methylated catecholamine metabolites for diagnosis of neuroblastoma

Assays of urinary catecholamines and their metabolites (HVA, VMA, dopamine) permit biochemical diagnosis of neuroblastoma in approximately 80% of patients. The urinary methylated catecholamine metabolites normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT) were analyzed in 18 patients with neuroblastoma and compared with reference values established for 69 healthy pediatric controls. All 18 neuroblastoma patients had raised urinary excretion of at least one of the three commonly assayed metabolites (HVA, VMA, dopamine). Similarly, raised urinary excretion of a methylated metabolite was noted in all but one of the neuroblastoma patients. The 3-MT level was pathologic in 16 of the 18 patients (89%). In this series, 3-MT assay sensitivity was sufficient to warrant trials on a larger population including comparison with patients considered nonsecretors by routine assay procedures. © 1992 Wiley-Liss, Inc.     

Cellular interactions between axon terminals containing endogenous opioid peptides or corticotropin-releasing factor in the rat locus coeruleus and surrounding dorsal pontine tegmentum

Recent evidence suggests that certain stressors release both endogenous opioids and corticotropin-releasing factor (CRF) to modulate activity of the locus coeruleus (LC)-norepinephrine (NE) system. In ultrastructural studies, axon terminals containing methionine(5)-enkephalin (ENK) or CRF have been shown to target LC dendrites. These findings suggested the hypothesis that both neuropeptides may coexist in common axon terminals that are positioned to have an impact on the LC. This possibility was examined by using immunofluorescence and immunoelectron microscopic analysis of the rat LC and neighboring dorsal pontine tegmentum. Ultrastructural analysis indicated that CRF- and ENK-containing axon terminals were abundant in similar portions of the neuropil and that approximately 16% of the axon terminals containing ENK were also immunoreactive for CRF. Dually labeled terminals were more frequently encountered in the "core" of the LC vs. its extranuclear dendritic zone, which included the medial parabrachial nucleus (mPB). Triple labeling for ENK, CRF, and tyrosine hydroxylase (TH) showed convergence of opioid and CRF axon terminals with noradrenergic dendrites as well as evidence for inputs to TH-labeled dendrites from dually labeled opioid/CRF axon terminals. One potential source of ENK and CRF in the dorsal pons is the central nucleus of the amygdala (CNA). To determine the relative contribution of ENK and CRF terminals from the CNA, the CNA was electrolytically lesioned. Light-level densitometry revealed robust decreases in CRF immunoreactivity in the LC and mPB on the side ipsilateral to the lesion but little or no change in ENK immunoreactivity, confirming previous studies of the mPB. Degenerating terminals from the CNA in lesioned rats were found to be in direct contact with TH-labeled dendrites. Together, these data indicate that ENK and CRF may be colocalized to a subset of individual axon terminals in the LC "core." The finding that the CNA provides, to dendrites in the area examined, a robust CRF innervation, but little or no opioid innervation, suggests that ENK and CRF axon terminals impacting LC neurons originate from distinct sources and that terminals that colocalize ENK and CRF are not from the CNA.