Expression of fructose-1,6-bisphosphatase 1 is associated with [18F]FDG uptake and prognosis in patients with mesial temporal lobe epilepsy.

OBJECTIVES: To determine whether fructose-1,6-bisphosphatase 1 (FBP1) expression is associated with [18F]FDG PET uptake and postsurgical outcomes in patients with mesial temporal lobe epilepsy (mTLE) and to investigate whether the molecular mechanism involving gamma-aminobutyric acid type A receptor (GABAAR), glucose transporter-3 (GLUT-3), and hexokinase-II (HK-II). METHODS: Forty-three patients with mTLE underwent [18F]FDG PET/CT. Patients were divided into Ia (Engel class Ia) and non-Ia (Engel class Ib-IV) groups according to more than 1 year of follow-up after surgery. The maximum standard uptake value (SUVmax) and asymmetry index (AI) of hippocampus were measured. The relationship among the SUVmax, AI, prognosis, and FBP1 expression was analyzed. A lithium-pilocarpine acute mTLE rat model was subjected to [18F]FDG micro-PET/CT. Hippocampal SUVmax and FBP1, GABAAR, GLUT-3, and HK-II expression were analyzed. RESULTS: SUVmax was higher in the Ia group than in the non-Ia group (7.31 ± 0.97 vs. 6.56 ± 0.96, p < 0.05) and FBP1 expression was lower in the Ia group (0.24 ± 0.03 vs. 0.27 ± 0.03, p < 0.01). FBP1 expression was negatively associated with SUVmax and AI (p < 0.01). In mTLE rats, the hippocampal FBP1 increased (0.26 ± 0.00 vs. 0.17 ± 0.00, p < 0.0001), and SUVmax, GLUT-3 and GABAAR levels decreased significantly (0.73 ± 0.12 vs. 1.46 ± 0.23, 0.20 ± 0.01 vs. 0.32 ± 0.05, 0.26 ± 0.02 vs. 0.35 ± 0.02, p < 0.05); no significant difference in HK-II levels was observed. In mTLE patients and rats, FBP1 negatively correlated with SUVmax and GLUT-3 and GABAAR levels (p < 0.05). CONCLUSION: FBP1 expression was inversely associated with SUVmax in mTLE, which might inhibit [18F]FDG uptake by regulating GLUT-3 expression. High FBP1 expression was indicative of low GABAAR expression and poor prognosis. KEY POINTS: • It is of paramount importance to explore the deep pathophysiological mechanisms underlying the pathogenesis of mesial temporal lobe epilepsy and find potential therapeutic targets. • [18F]FDG PET has demonstrated low metabolism in epileptic regions during the interictal period, and hypometabolism may be associated with prognosis, but the pathomechanism of this association remains uncertain. • Our results support the possibility that FBP1 might be simultaneously involved in the regulation of glucose metabolism levels and the excitability of neurons and suggest that targeting FBP1 may be a viable strategy in the diagnosis and treatment of mesial temporal lobe epilepsy.

Neuronal Alterations in Secondary Thalamic Degeneration Due to Cerebral Infarction: A 11C-Flumazenil Positron Emission Tomography Study.

BACKGROUND: Studies using animal experiments have shown secondary neuronal degeneration in the thalamus after cerebral infarction. Neuroimaging studies in humans have revealed changes in imaging parameters in the thalamus, remote to the infarction. However, few studies have directly demonstrated neuronal changes in the thalamus in vivo. The purpose of this study was to determine whether secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease. METHODS: We retrospectively analyzed the data of 140 patients with unilateral cerebral infarction ipsilateral to internal carotid artery or middle cerebral artery disease. All patients had quantitative measurements of 11C-flumazenil binding potential (FMZ-BP), cerebral blood flow, and cerebral metabolic rate of oxygen using positron emission tomography in the chronic stage. Region of interest analysis was performed using NeuroFlexer-an automated region of interest analysis software using NEUROSTAT. RESULTS: In the thalamus ipsilateral to the infarcts, the values of FMZ-BP, cerebral blood flow, and cerebral metabolic rate of oxygen were significantly lower than those in the contralateral thalamus. Significant correlations were found between the ipsilateral-to-contralateral ratio of FMZ-BP and the ipsilateral-to-contralateral ratio of cerebral blood flow or cerebral metabolic rate of oxygen in the thalamus. Patients with corona radiata infarcts and striatocapsular infarcts had significantly decreased ipsilateral-to-contralateral FMZ-BP ratio in the thalamus compared with those without. The ipsilateral-to-contralateral ratio of FMZ-BP in the thalamus was significantly correlated with the ipsilateral-to-contralateral cerebral metabolic rate of oxygen ratio in the frontal cortex and showed a significant negative correlation with the number of perseverative errors on the Wisconsin Card Sorting Test. CONCLUSIONS: Secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease, which may be associated with frontal lobe dysfunction.

[Etomidate for intravenous induction of anaesthesia]. / Medikamente zur intravenösen Narkoseinduktion: Etomidat.

The pharmacological and historical knowledge about the currently available intravenous induction hypnotics form the basis for the daily work of anesthetists. Side effects of using hypnotic induction agents must be anticipated and adequately treated. Decades of experience with using intravenous induction hypnotics have led to theoretical requirements for an ideal narcotic agent with a best possible side effect profile. In the absence of this optimal hypnotic induction agent, a careful selection of one or a combination of narcotic drugs is necessary to meet the needs of the respective risk constellation of the patient. While propofol enjoyed increasing frequency of use over the last three decades and is currently regarded as the gold standard in numerous clinics, thiopental is a noteworthy alternative apart from its elimination kinetics. Furthermore, substances with favorable hemodynamic profiles are available with etomidate and ketamine. Midazolam as a short-acting benzodiazepine rounds off the spectrum.

Effects of moderate sedation induced by propofol or midazolam on intracranial pressure

Introduction: Propofol and midazolam are the main options for moderate sedation in clinical practice. In addition, these drugs are used to reduce intracranial pressure in cases of intracranial hypertension, and their use in these situations is guided by limited evidence. Objective: To compare the effects of propofol and midazolam on intracranial pressure wave morphology in moderate sedation in patients undergoing upper digestive endoscopy. Methods: Sixty patients were included in this study, being divided into two groups, propofol and midazolam group. Intracranial pressure was monitored during and after upper digestive endoscopy, using non-invasive monitoring equipment developed by the company Brain4care. Arterial pressure was measured before and after the exam. Results: The propofol group had lower intracranial pressure (p=0.037) during moderate sedation compared to intracranial pressure after endoscopy and a significant decrease in systolic (p=0.0001) and diastolic pressure (p=0.001) after sedation. Midazolam, on the other hand, reduced systolic pressure (p=0.001), but didn't change the other parameters after the procedure. There wasn't a significant difference between the propofol and midazolam groups. Conclusion: There was no significant difference between the groups studied, however, analyses within the propofol and midazolam groups indicate that propofol, but not midazolam, causes changes in intracranial pressure in moderate sedation.

Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABAAR antibodies.

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) has been described as an epileptic encephalopathy of unknown etiology affecting previously healthy children following febrile illness. Despite large investigations on autoimmune pathogenesis no membrane antibodies has been associated since now. CASE STUDY: We report a 13 years-old girl with negative history for neurological or autoimmune disease that developed at the sixth day of high fever a super-refractory status epilepticus. All investigations, including the most common antibodies related to immune-mediated encephalitis were negative. Seizures continued despite several therapeutic trials with anesthetics (midazolam, propofol) and antiepileptic agents as well as i.v. immunoglobulins but responded, at day 10 from the onset, to ketamine and high dose i.v. steroids. Due the high suspicion of autoimmune encephalitis we tested patient's CSF and plasma on mouse brain with positive response. We subsequently detected a high titre of GABAAR antibodies. After the resolution of the status epilepticus the patient achieved complete recovery of neurological functions. CONCLUSION: this is the first reported case of a FIRES-like condition due to autoimmune encephalitis mediated by GABAAR antibodies. Our case suggests that GABAAR antibodies should be investigated FIRES.

Phytohormone abscisic acid boosts pentobarbital-induced sleep through activation of GABA-A, PPARß and PPARγ receptor signaling / O fito-hormônio ácido abscísico estimula o sono induzido por fenobarbital por meio de ativação da sinalização de receptores GABA-A, PPARß e PPARγ

ABSTRACT Background: Sleep disorders induce anxiety and forgetfulness and change habits. The chemical hypnotic drugs currently used have serious side effects and, therefore, people are drawn towards using natural compounds such as plant-based healing agents. Abscisic acid (ABA) is produced in a variety of mammalian tissues and it is involved in many neurophysiological functions. Objective: To investigate the possible effect of ABA on pentobarbital-induced sleep and its possible signaling through GABA-A and PPAR (γ and β) receptors, in male Wistar rats. Methods: The possible effect of ABA (5 and 10 µg/rat, intracerebroventricularly) on sleep onset latency time and duration was evaluated in a V-maze model of sleep. Pentobarbital sodium (40 mg/kg, intraperitoneally) was injected to induce sleep 30 min after administration of ABA. PPARβ (GSK0660, 80 nM/rat), PPARγ (GW9662, 3 nM/rat) or GABA-A receptor (bicuculline, 6 µg/rat) antagonists were given 15 min before ABA injection. Diazepam (2 mg/kg, intraperitoneally) was used as a positive control group. Results: ABA at 5 µg significantly boosted the pentobarbital-induced subhypnotic effects and promoted induction of sleep onset in a manner comparable to diazepam treatment. Furthermore, pretreatment with bicuculline significantly abolished the ABA effects on sleep parameters, while the amplifying effects of ABA on the induction of sleep onset was not significantly affected by PPARβ or PPARγ antagonists. The sleep prolonging effect of ABA was significantly prevented by both PPAR antagonists. Conclusions: The data showed that ABA boosts pentobarbital-induced sleep and that GABA-A, PPARβ and PPARγ receptors are, at least in part, involved in ABA signaling.

RESUMO Introdução: Os distúrbios do sono induzem a ansiedade e esquecimento e mudam hábitos. Os medicamentos hipnóticos químicos utilizados atualmente têm efeitos colaterais graves e, portanto, as pessoas são atraídas para o uso de compostos naturais, como agentes de cura à base de plantas. O ácido abscísico (ABA) é produzido em uma variedade de tecidos de mamíferos e está envolvido em muitas funções neurofisiológicas. Objetivo: Investigar o possível efeito do ABA no sono induzido por pentobarbital e sua possível sinalização por meio dos receptores GABA-A e PPAR (γ e β), em ratos Wistar machos. Métodos: O possível efeito do ABA (5 e 10 µg/rato, intracerebroventricularmente) no tempo de latência e duração do início do sono foi avaliado em um modelo de labirinto em V de sono. Pentobarbital sódico (40 mg/kg, intraperitonealmente) foi injetado para induzir o sono 30 minutos após a administração de ABA. PPARβ (GSK0660, 80 nM/rato), PPARγ (GW9662, 3 nM/rato) ou antagonistas do receptor GABA-A (bicuculina, 6 µg/rato) foram administrados 15 minutos antes da injeção de ABA. Diazepam (2 mg/kg, intraperitonealmente) foi utilizado como grupo de controle positivo. Resultados: ABA a 5 µg aumentou significativamente os efeitos sub-hipnóticos induzidos por pentobarbital e promoveu a indução do início do sono de forma comparável ao tratamento com diazepam. Além disso, o pré-tratamento com bicuculina aboliu significativamente os efeitos do ABA nos parâmetros do sono, ao passo que os efeitos amplificadores do ABA na indução do início do sono não foram significativamente afetados pelos antagonistas do PPARβ ou PPARγ. O efeito de prolongamento do sono do ABA foi significativamente prevenido por ambos os antagonistas do PPAR. Conclusões: Os dados mostraram que o ABA estimula o sono induzido por pentobarbital e que os receptores GABA-A, PPARβ e PPARγ estão, pelo menos em parte, envolvidos na sinalização ABA.

Effect of oxycodone on function of GABAA receptors in dorsal root ganglion neurons of rats with neuropathic pain / 中华麻醉学杂志

Objective To evaluate the effect of oxycodone on function of GABAA receptors in dor-sal root ganglion ( DRG ) neurons of rats with neuropathic pain ( NP ) . Methods Thirty-six adult male Sprague-Dawley rats, weighing 180-220 g, aged 10 weeks, were allocated into 3 groups ( n=12 each) u-sing a random number table method: sham operation group ( group S ) , group NP and oxycodone group ( group O) . The sciatic nerve was only isolated but not ligated in group S. NP was induced by chronic con-striction injury. The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut. Oxycodone 15μg∕kg was intraperitoneally injected once a day for 14 con-secutive days from ligating the sciatic nerve to satisfaction in group O. The thermal paw withdrawal latency( TWL) was measured at 1 day before establishing the model ( T0 ) and 3, 5, 7, 10 and 14 days after es-tablishing the model ( T1-5 ) . The rats were sacrificed after measurement of pain threshold at T5 , and DRG neurons were acutely isolated for recording the amplitude of GABAA receptors-activated currents using whole-cell patch-clamp technique. Results Compared with group S, the TWL was significantly shortened at T1-5, and the amplitude of GABAA receptors-activated currents in DRG neurons was decreased in NP and O groups (P<0. 05). Compared with group NP, the TWL was significantly prolonged at T1-5, and the ampli-tude of GABAA receptors-activated currents in DRG neurons was increased in group O ( P<0. 05) . Conclu-sion Oxycodone can enhance the function of GABAA receptors-activated currents in DRG neurons and thus enhance GABAA receptors-mediated presynaptic inhibition, which may be related to the mechanism of oxyc-odone-induced reduction of NP in rats.

Effects of different ratios of medicine dosage for isoflurane and propofol on GABAAreceptor α1sub-unit proteostasis during hypoxia injury to hippocampal neurons of rats / 中华麻醉学杂志

Objective To evaluate the effects of different ratios of medicine dosage for isoflurane and propofol on GABAAreceptor(GABAAR)α1subunit proteostasis during hypoxia injury to hippocampal neurons of rats. Methods The hippocampal neurons isolated from fetal rats obtained from Wistar rats were primarily cultured and divided into 6 groups(n=60 each)using a random number table: control group (group C), hypoxia group(group H), isoflurane group(group I), propofol group(group P)and dif-ferent ratios of medicine dosage for isoflurane and propofol groups(group IP1and group IP2). The cells were subjected to hypoxia for 6 h in group H. Cells were incubated for 3 h with 1.9 % isoflurane and with 22.4 μmol∕L propofol after being subjected to hypoxia for 6 h in I and P groups, respectively. Cells were incubated for 3 h with 1.0% isoflurane and 6.7 μmol∕L propofol and with 1.4% isoflurane and 3.4 μmol∕L propofol after being subjected to hypoxia for 6 h in IP1and IP2groups, respectively. Then the culture medi-um was replaced with plain culture medium. At 24 h of incubation, the cells were collected for measure-ment of cell viability by CCK-8 assay, GABAAR α1mRNA expression(by quantitative polymerase chain reaction), GABAAR α1expression in the cytomembrane(by Western blot), level of GABAAR α1subunit endoplasmic reticulum-associated degradation(ERAD)(by immunoprecipitation and Western blot)and CCAAT∕enhancer-binding protein homologous protein(CHOP)expression(by immunofluorescence). Re-sults Compared with group C, the cell viability was significantly decreased, the expression of GABAAR α1mRNA and GABAAR α1in cytomembrane was down-regulated, the expression of CHOP was up-regula-ted, and the level of GABAAR α1subunit ERAD was increased in the other five groups(P<0.05). Com-pared with group H, the cell viability was significantly decreased, the expression of GABAAR α1mRNA and GABAAR α1in cytomembrane was down-regulated, the expression of CHOP was up-regulated, and the level of GABAAR α1subunit ERAD was increased in I, P and IP2groups(P <0.05), and no significant change was found in the parameters mentioned above in group IP1(P<0.05). Compared with group I or group P, the cell viability was significantly increased, the expression of GABAAR α1mRNA and GABAAR α1 in cytomembrane was up-regulated, the expression of CHOP was down-regulated, and the level of GABAAR α1subunit ERAD was decreased in IP1and IP2groups(P<0.05). Compared with group IP1, the cell viability was significantly decreased, the expression of GABAAR α1mRNA and GABAAR α1in cy-tomembrane was down-regulated, the expression of CHOP was up-regulated, and the level of GABAAR α1 subunit ERAD was increased in group IP2(P<0.05). Conclusion Combination of 1.0% isoflurane and 6.7 μmol∕L propofol does not aggravate hypoxia-induced destruction of GABAAR α1subunit proteostasis in hippocampal neurons of rats.

A prescrição de benzodiazepínicos no Brasil: uma análise da literatura / The prescription of benzodiazepines in Brazil: a literature review

Benzodiazepínicos são medicamentos psicotrópicos de prescrição restrita e sujeitos a controle especial, conforme a Portaria nº 344, de 12 de maio de 1998. São utilizados como hipnóticos e sedativos, sendo bastante comuns na prática clínica. O uso prolongado destes fármacos pode causar dependência e por isso é necessário identificar seu perfil de prescrição. Este estudo busca revisar a literatura sobre os trabalhos que descreveram o uso de benzodiazepínicos no Brasil. Para isso, uma busca direta foi realizada em três bases de dados, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), PubMed e Scientific Eletronic Library Online (SciELO), utilizando os descritores prescrição/prescription, benzodiazepínicos/benzodiazepines, Brasil/Brazil. Depois de aplicados os critérios de inclusão e exclusão, restaram 12 artigos, os quais foram analisados. A análise destes trabalhos mostrou que, no Brasil, os benzodiazepínicos são utilizados especialmente por mulheres com tendência ao aumento do uso com o avançar da idade. Desta maneira, conclui-se que permanece a necessidade de políticas públicas que busquem o uso racional destes fármacos.

Benzodiazepines are prescription restricted psychotropic drugs, subject to special control according to Decree nº 344 of May 12, 1998. They are used as hypnotics and sedatives, being widely used in clinical practice. Prolonged use of these drugs can cause dependence, and therefore it is necessary to identify their prescription profile. This study aims to review the literature on studies that described the use of benzodiazepines in Brazil. For such, a direct search was conducted in databases, such as LILACS, Pubmed and SciELO, with the descriptors, in Portuguese and English, "prescrição" (prescription), "benzodiazepínicos" (benzodiazepines) and "Brasil" (Brazil). After applying the criteria for inclusion and exclusion, 12 articles remained, which were analyzed in this work. The analysis of these data has shown that, in Brazil, benzodiazepines are used especially by women with a tendency to increased use with advancing age. On this wat, we might conclude that Brazil's needs to improve his politics to promote rational use of Benzodiazepines.

Utilização de benzodiazepínicos e estratégias farmacêuticas em saúde mental / Use of benzodiazepines and drug strategies in mental health

O artigo enfoca a heterogeneidade no uso de benzodiazepínicos, sob o enfoque farmacêutico, observada nos Centros de Atenção Psicossocial e Unidades Básicas de Saúde da Família. Os benzodiazepínicos estão incluídos entre os medicamentos mais prescritos para tratar distúrbios de ansiedade. Os avanços da reforma psiquiátrica, a criação dos Centros de Atenção Psicossocial (Caps) e o redirecionamento das atividades de saúde primária tornam imperiosa a adequação da prática farmacêutica através de atividades de orientação e acolhimento ao usuário de benzodiazepínicos.

This article focuses on the discrepancies in the use of benzodiazepines, under the pharmaceutical approach, observed daily in Centers of Psychosocial Care (Caps) and in Basic Units of Family Health. Benzodiazepines are among the most prescribed medications for the treatment of anxiety disorders. Advances in psychiatric reform, the creation of Caps and the new approach to primary health activities make imperative the adequacy of pharmaceutical practice through guidance and care activities to benzodiazepines' users.

Effects of midazolam on GABAA receptor-activated currents in isolated dorsal root ganglion neurons in rats / 中华麻醉学杂志

Objective To investigate the effects of midazolam on GABAA receptor-activated currents in isolated dorsal root ganglion (DRG) neurons in rats.Methods Sprague-Dawley rats of both sexes,weighing 200-250 g,aged 4 weeks,were used in the study.The DRG neurons were isolated and GABAA receptor-activated currents were recorded using the whole-cell patch-clamp technique.GABAA receptor-activated currents were recorded after administration of the mixture of midazolam 3.00 μmol/L (final concentration)and the different final concentrations (0.03,0.10,1.00,10.00,100.00 and 1000.00 μmol/L) of GABA,after different concentrations of midazolam (0.03,0.10,1.00,3.00,10.00 and 100.00 μmol/L) was given,after administration of the mixture of different final concentrations(0.03,0.10,1.00,3.00,10.00 and 100.00 μmol/L) of midazolam and GABA 100.00 μmol/L (final concentration),and after administration of the mixture of midazolam 1.00μmol/L (final concentration) and GABA 100.00 μmol/L (final concentration)at the preset time points of perfusion with different concentrations of midazolam (0,20,40,60 and 120 s of perfusion).The enhancement rate of the currents was calculated.Results No change in the membrane currents was found after midazolam was perfused in the neurons sensitive to GABA.GABAA receptor-activated currents were enhanced after administration of the mixture of different concentrations of GABA and midazolam.GABAA receptor-activated currents were enhanced after different concentrations of midazolam were given compared with that before administration,and the enhancement rate of the GABAA receptoractivated currents was gradually increased with the increase in the concentration of midazolam and reached the peak at the concentration of 3.00 μmol/L.The enhancement rate of the GABAA receptor-activated currents was gradually increased with the prolongation of perfusion time and peaked at 40 s of perfusion.Conclusion Midazolam can enhance the GABAA receptor-activated currents in rat dorsal root ganglion neurons,indicating that midazolam increases the role of GABA through increasing the activity of GABAA receptors and has analgesic effect at the spinal cord level.

Role of gamma-aminobutyric acid A receptor in lung tissues in lipopolysaccharide-induced acute lung injury in rats / 中华麻醉学杂志

Objective To investigate the role of gamma-aminobutyric acid (GABA) A receptor (GABAAR) in lung tissues in lipopolysaccharide (LPS)-induced acute lung injury in rats.Methods Thirty-two male Wistar rats,aged 8 weeks,weighing 200-230 g,were randomly divided into 4 groups (n =8 each) ∶ control group (group C),group LPS,GABA pretreatment + LPS group (group GABA) and GABAAR antagonist bicuculline pretreatment + LPS group (group BIC).Acute lung injury was induced by intravenous LPS 5 mg/kg in groups LPS,GABA and BIC,while the equal volume of normal saline was given in group C.GABA 50 mg/kg and bicuculline 10 μmol/kg were injected intraperitoneally 30 min before LPS injection in GABA and BIC groups,respectively.Arterial blood samples were collected at 6 h after LPS injection for measurement of arterial partial pressure of oxygen (PaO2).The animals were then sacrificed and lungs removed for determination of W/D lung weight ratio,GABAAR expression,contents of interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) and superoxide dismutase (SOD) activity in lung tissues and for microscopic examination.Results Compared with group C,PaO2 was significantly decreased in the other three groups,and W/D lung weight ratio,TNF-α,IL-6 and MDA contents were significantly increased,GABAAR expression was up-regulated,and SOD activity was decreased in groups LPS and GABA (P ＜ 0.05).Compared with group LPS,W/D lung weight ratio,TNF-α,IL-6 and MDA contents were significantly increased,GABAAR expression was up-regulated,and SOD activity was decreased in group GABA (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group BIC and in PaO2 in groups GABA and BIC (P ＞ 0.05).Conclusion GABAA R in lung tissues is involved in the development of acute lung injury induced by LPS.

Role of spinal cord GABAA receptors in the analgesic effect of propofol on visceral pain in rats / 中华麻醉学杂志

Objective To evaluate the role of spinal cord CABAA receptors in the analgesic effect of propofol on visceral pain in rats. Methods Adult female SD rats, weighing 190-240 g, were used in this study.The animals were anesthetized with intraperitoneal ketamine 50-100 mg/kg. Intrathecal (IT) catheters were placed at L5-6 interspace according to the technique described by Storkson et al. Thirty-two animals in which IT catheters were successfully placed were randomly divided into 4 groups ( n = 8 each) : dimethyl sulphoxide (DMSO) group (group D), propofol group (group P), bicuculline group (group B) and bicuculline + propofol group (group B +P). Visceral pain was induced by injecting 10% formalin 100 μl underneath the mucous membrane of rectum.Groups D, P and B received IT DMSO 5 μl, propofol 10 μg and bicuculline 2 μg respectively. Group BP received IT bicuculline 2 μg and then IT propofol 10 μg 10 min later. The L5-S1 segment of the spinal cord was removed 2 h after formalin injection to determine FOS protein expression by hnmuno-histochemistry. Results Compared with groups D and B, FOS protein expression was significantly down-regulated in group P ( P ＜ 0.05 ) . There was no significant difference in FOS protein expression between groups D and B ( P ＞ 0.05) . FOS protein expression was significantly up-regulated in group BP compared with group P ( P ＜ 0.05) . Conclusion Propofol has analgesic effect on visceral pain in rats through spinal cord GABAA receptor action.

Role of GABAA receptors in uninjured dorsal root ganglion in a rat model of neuropathic pain / 中华麻醉学杂志

Objective To evaluate the role of GABAA receptors in uninjured dorsal root ganglion(L4DRG)in a rat model of neuropathic pain.Methods Thirty adult female SD rats weighing 200-250 g were randomly divided into 3 groups(n = 10 each): control group(group C),muscimol group(group M)and bicuculline group(group B).Neuropathic pain was produced by L5 spinal nerve ligation.Normal saline 50 μl,GABAA receptor agonist-muscimol 50 μl or GABAA receptor antagonist- bicucullin 50 μl was injected into the L4 DRG.The thermal pain threshold and mechanical pain threshold were measured and recorded from 1 day before operation to 10 days after operation.Results Compared with group C,the mechanical pain threshold was significantly increased(P ＜ 0.05),while no significant difference was found in thermal pain threshold in group M(P ＞ 0.05),and the thermal pain threshold and mechanical pain threshold were significantly decreased in group B(P ＜ 0.05).Conclusion Activation of GABAA receptors in uninjured DRG is involved in mechanical hyperalgesia in a rat model of neuropathic pain,but it dose not play a leading role.

Peripheral benzodiazepine receptors and cerebral ischemia / 国际脑血管病杂志

1he increased peripheral benzodiazepine receptors are more significant than normal ones after cerebral ischemia. Its main reactions are the multiple pathological changes,including microglial activation, participating in neuroinflammation response, and regulation of mitochondrial function. Using radionuclide-laheled specific ligands of the peripheral benzodiaz-epine receptor (such as PK11195) for in vivo imaging contribute to the location and quantitative detection for brain injury and the study of the pathophysiological changes after cerebral ischemi-a. In addition, this receptor is promising to become a new target of neuroprotective treatment.This article reviews the recent progress in research on peripheral benzodiazepine receptors and cerebral ischemia.

Contents of amino acid neurotransmitters and expression of GABAA receptor subunits' mRNA in subareas of basal ganglia in unilateral rat model of Parkinson's disease / 中华神经科杂志

Objective To explore contents of amino acid neurotransmitters and expression of GABAAreceptor subunits'mRNA in subareas of basal ganglia in unilateral rat model of Parkinson's disease (PD).Methods The rat model of PD was established through right unilateral intranigral microinjection of 6-hydroxydopamine(6-OHDA)in this study.Thawed samples were taken form neostriatum(Str).globus pallidus internus(Gpi),globus pallidus externum(Gpe)and subthalamic nucleus(STN).then contents of amino acid neurotransmitters were analyzed by established high performance liquid chromatography (HPLC)-electrochemical detection methods.The subunits α1,α2,β2/3 and γ2 of GABAA receptor in Str,Gpi,Gpe and STN wre examined with Northern Enzyme linked immunosorbent assay(ELISA).Results The content of GABA in Str,Gpi,Gpe and STN of diseased side were significantly increased as compared with undiseasedside.The level of glutamic acid(Glu)in Str,Gpe and STN and contents of aspartic acid (Asp)and glycine(Gly)in STN of the diseased side were significantly increased.In Str.there was a significant decrease of mRNA expression either in the subunit α1(105.3±24.5)or in the subunit β2/3(113.7 ±15.3)of GABAA receptor in the diseased side as compared with the undiseased 8ide(186.7 ±37.2,157.4±32.4,t=5.16,3.45;P<0.01).In Gpi,there was a significant increase of mRNA expression in the subunit α1(P<0.05)and α2,β2/3(P<0.01)of GABAA receptor in lesion side.In Gpe,there was a significant decrease of mRNA expression in the subunit α2(179.1±26.8)andβ2/3(154.7 ±37.8)of GABAA receptor in the diseased side(219.3.±19.7,231.1±55.8,t=3.42,3.21:P<0.01).In STN of right unilateral 6-0HDA lesion rat.there was a significant decrease of mRNA expression both in the subunitα1,α2 and β2/3(P<0.01)of GABAA receptor and in the subunit γ2(P<0.05)of GABAA receptor in the diseased side.Conclusions Changes of amino acid neurotransmitter contents and GABAA receptor subunits'mRNA expressional level in subareas of basal ganglia may be involved in PD.

Benzodiazepine use among employees of a private company / Consumo de benzodiazepinas en trabajadores de una empresa privada / Consumo de benzodiazepinas por trabalhadores de uma empresa privada

This study aimed to identify variables associated to the consumption of benzodiazepine among workers of a private company in the VIII Region, Chile. This is a cross-sectional and correlative study. Study population: 40 employees of a private company. The instruments included a questionnaire on socio-demographic variables and a benzodiazepine questionnaire. There was no record of benzodiazepine consumption at the moment of the study. Twenty percent (20 percent) of the interviewees had already used benzodiazepine in the past, whereas, half of them (10 percent) in the last year. The bivariate analysis of the last year consumption of benzodiazepine with work hours variables showed no significant relation (p=0.073). No association was found between benzodiazepine consumption and socio-demographic variables among the study participants.

El propósito de este estudio fue identificar las variables asociadas al consumo de benzodiazepinas en población trabajadora de una institución privada de la VIII Región, Chile. Diseño cuantitativo, transversal y correlacional. Población del estudio: 40 trabajadores de una empresa privada de la VIII Región, Chile. Instrumentos recolectores de datos. Cuestionario de variables biosociodemográficas y Cuestionario de benzodiazepinas. No se registró consumo de benzodiazepinas al momento del estudio. 20 por ciento de los entrevistados tenía antecedentes de consumo de benzodiazepinas en el pasado, de ellos la mitad (10 por ciento) en el último año. El análisis bivariado del consumo de benzodiazepinas en el último año con variables del trabajo sólo mostró una relación débilmente significativa (p= 0,073) con la jornada de trabajo. No se encontró asociación entre el consumo de benzodiazepines y las variables sociodemográficas entre los participantes del estudio.

O propósito deste estudo foi avaliar as variáveis associadas ao consumo de benzodiazepínicos em população trabalhadora de uma instituição privada da VIII Região, Chile. Este é um estudo quantitativo, transversal e correlacional. Participaram do estudo 40 trabalhadores de uma empresa privada da VIII Região, Chile. Para coleta dos dados utilizou-se um questionário com informações relacionadas às variáveis sócio-demográficas e Questionário de benzodiazepínicos. Não foi identificado consumo de benzodiazepínicos no momento do estudo. Constatou-se que 20 por cento dos entrevistados tinham antecedentes de consumo de benzodiazepínicos e, destes, a metade (10 por cento), no último ano. A análise bivariada do consumo de benzodiazepínicos no último ano com variáveis relacionadas ao trabalho mostrou uma relação pouco significativa (p= 0,073) com jornada de trabalho. Não foi identificada associação entre o consumo de benzodiazepínicos e as variáveis sócio-demográficas entre os participantes deste estudo.

Effects of estrogen, clomiphene on gamma-aminobutyric acid immunoreactive cell and ?1 subunit of GABA_A receptor in hippocampus of epileptic rats / 中华神经科杂志

Objectives To find out the effects of estrogen and clomiphene on behavior of epileptic rats induced by kainic acid (KA) and probe into some mechanisms. Methods Ovariectomized Sprague-Dawley female rats were treated with estrogen (E) or estrogen and clomiphene (C). Their behaviors when they were induced seizures were observed and compared. Indirect immunofluorescence method was used to measure the alterations of gamma-aminobutyric acid (GABA) immunoreactive cells and ?1 subunits of GABA_A receptors in the hippocampus of all groups. Results The latency and time at reaching 4/5 degrees in KA+E group ((24.63?11.44) minutes and (41.50?16.22) minutes, respectively) were reduced greatly than KA group ((46.75?14.61) minutes and (65.13?12.99) minutes), while the latency of (KA+)E+C group (adding estrogen and clomiphene, (43.50?5.75) minutes) became prolonged significantly than in KA+E group. Conclusion High-level estrogen should be proconvulsant and the clomiphene might have some antiepileptic effects, which may be related with some alterations of GABA energic function in the brain.

Relationship between sevoflurane and GABA_A receptors / 中华麻醉学杂志

005); (3)When sevoflurane concentrations were in the range from 1556?mol/L to 5875?mol/L ,the KD of experimental groups was significantly lower than that of the control (P

Long-term effects of neonatal recurrent seizures on ?-aminobutyric acid A receptor ?1 and ?2 subunit expressions in the rat brain / 北京大学学报(医学版)

0.05).The AOD of ?2 subunit protein immunoreactivity in the frontal lobe and CA4 region decreased significantly in the seizure group than those in the control group(P0.05),but the expressions of ?1 subunits mRNA in the hippocampus and ?2 subunit mRNA in the cerebral cortex in the seizure group decreased significantly as compared with those in the control group(P