Mechanism of the cerebrovascular effect of piracetam

Piracetam produces a more pronounced effect on cerebral circulation disturbed by hemorrhagic shock as compared with intact animals. Piracetam has a depressant effect on the nervous regulation of cerebral circulation by suppressing the reflex constriction of the vessels in both arterial systems of the brain. The cerebrovascular effects of piracetam are not mediated through the GABAergic bicuculline-sensitive mechanisms, which is supported by experiments where the drug exhibits its effects under the blockade of GABA receptors.     

中药银杏叶对老年痴呆症小鼠学习记忆能力的影响

目的研究中药银杏叶与西药脑复康片对老年痴呆症小鼠学习记忆能力恢复效果的差异。方法 KM小鼠随机分为对照组、模型组、银杏叶组和脑复康组,各组20只。除对照组外,其余组采用腹腔注射D-半乳糖和灌胃AlCl3进行造模,连续60 d。银杏叶组和脑复康组自造模起给予相应的药物,连续60 d。试验结束后测定小鼠学习记忆能力,测定脑组织中乙酰胆碱酯酶活性、过氧化脂质（MDA）含量、超氧化岐化酶（SOD）活性、Na＋、K＋-ATPase、游离钙离子含量和进行脑神经元细胞计数。结果与模型组比较,银杏叶组动物潜伏期明显延长,错误次数降低（P〈0.05）;银杏叶组动物脑组织SOD活性明显升高（P〈0.05）,MDA含量、Ca＋浓度含量、乙酰胆碱酯酶活性显著性降低（P〈0.05）,与对照及脑复康组比较未见显著差异（P〉0.05）;银杏叶组动物大脑海马锥体细胞数与模型组比较明显升高（P〈0.01）,大脑皮质神经元细胞数与模型组比较无明显差异（P〉0.05）。结论中药银杏叶改善小鼠学习记忆障碍的作用与西药脑复康片相似。     

Piracetam Prevents Scopolamine-Induced Memory Impairment and Decrease of NTPDase, 5′-Nucleotidase and Adenosine Deaminase Activities

Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5′-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5′-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5′-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5′-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.     

Effects of heptapeptide of the tuftsin group with nootropic components of action and piracetam on formation of escape reaction in normal conditions and in conflict situation

In this work we have compared the effect of Tuftsin Group synthetic heptapeptide (TP-1) and Piracetam on learning of avoidance response and its restoring after disturbance provoked by unexpected changes of previously established cause-effect relations in experimental environment. We have pointed out that both of the drugs improve learning but the dynamics is different, namely: Piracetam causes the greatest improvement on the 1st day, meanwhile the Heptapeptide--on the 4th day. Both of them preclude from disturbing avoidance response and this protective action of peptide is more effective.     

Early Undernutrition and [3H]γ-Aminobutyric Acid Binding in Rat Brain

The effect of early undernutrition and dietary rehabilitation on [3H]gamma-aminobutyric acid ([3H]GABA) binding in rat brain cerebral cortex and hippocampus was examined. Undernourished animals were obtained by exposing their mothers to a protein-deficient diet during both gestation and lactation. Saturation analysis of [3H]GABA binding in the cerebral cortex and hippocampus revealed high- and low-affinity components in the undernourished group, whereas control animals possessed only a low-affinity site. The concentration of low-affinity binding sites was greater in the undernourished animals. Rehabilitation of undernourished animals completely abolished the binding site differences. Treatment of brain membranes with Triton X-100 yielded two binding components in both the undernourished and control animals, although the concentration of lower affinity sites was still greater in the undernourished group. Neither the efficacy nor the potency of GABA to activate benzodiazepine binding in cerebral cortex was modified by undernutrition. These data suggest that early undernourishment modifies the characteristics of [3H]GABA binding, perhaps by reducing the brain content of endogenous inhibitors of the higher affinity binding site. The lack of effect on GABA-activated benzodiazepine binding suggests the possibility that neither the high- nor the low-affinity GABA binding sites are coupled to this receptor component.     

The metabolism of arachidonic acid to an antiaggregatory compound in isolated lungs of fetal and neonatal rabbits

The developmental pattern of fetal and neonatal rabbit lungs to generate an antiaggregatory compound from arachidonic acid (AA) was studied in isolated rabbit lungs, which were perfused with Krebs bicarbonate buffer. The antiaggregatory effect of the nonrecirculating perfussion effluent was tested by adding a small portion of the effluent to human platelet rich plasma (PRP) in a Born-type aggregometer before the aggregation was induced by ADP. The production of an antiaggregatory compound was minimal, when exogenous AA was not infused into the pulmonary circulation. When arachidonate (40 nmol/min) was infused into the pulmonary circulation of rabbits which were 1 day or 1 week old, the perfusion effluent significantly inhibited the ADP induced aggregation of PRP. Perfused lungs from fetal rabbits (gestation age 28–31 days) formed also an antiaggregatory compound fro AA, but the antiaggregatory effect was not as great as 1 day after birth. It seems that neonatal rabbit lungs metabolize AA more to an antiaggregatory compound than late fetal lungs. The fact that the AA induced production of an antiaggregatory compound is inhibited by simultaneous infusion of indomethacin favours the hypothesis that this antiaggregatory compound could he PGI₂.     

马桑内酯激活的星形胶质细胞条件培养液对正常大鼠脑内谷氨酸和GABA的影响

目的探讨星形胶质细胞对大鼠脑内谷氨酸(Glu)和γ-氨基丁酸(GABA)的影响及其在癫痫发病中的作用。方法将马桑内酯激活的星形胶质细胞条件培养液(astrocyte-conditioned medium,ACM)注射入正常SD大鼠侧脑室,观察大鼠的行为变化,运用免疫组织化学及HPLC的方法,观察大鼠大脑皮质、海马内Glu和GABA免疫反应的变化及脑组织匀浆、脑脊液内Glu和GABA含量的变化。结果ACM组大鼠在注射ACM后30min出现癫痫行为,2h恢复正常。免疫组织化学显示:ACM作用后2h,大鼠大脑皮质及海马内Glu免疫反应阳性神经元数和平均光密度值明显增高,4h达高峰(P<0.05),12h恢复正常水平;ACM作用后2h,大鼠大脑皮质及海马GABA免疫反应阳性神经元数和平均光密度值明显减弱(P<0.05),12h恢复正常水平。HPLC方法显示:ACM作用后2h大鼠大脑皮质、海马及脑脊液中Glu含量均开始增加,4h达高峰(P<0.05);ACM作用后2h大脑皮质、海马及脑脊液中GABA含量均开始降低,4h达最低(P<0.05)。结论马桑内酯激活的星形胶质细胞条件培养液可影响大鼠脑内Glu和GABA的表达,并导致动物痫性发作。     

In Vivo Changes in γ-Aminobutyric Acid Output from the Cerebral Cortex Induced by Inhibitors of γ-Aminobutyric Acid Uptake and Metabolism

Abstract: The effects of inhibitors of γ-aminobutyric acid (GABA) metabolism or uptake on GABA output from the cerebral cortex was studied by means of a collecting cup placed on the exposed cortex of rats anaesthetized with urethane. GABA was identified and quantified by a mass-fragmentographic method. Ethanolamine-O-sulphate (10⁻² M ) applied directly on the cerebral cortex caused a long-lasting twofold increase in GABA output, whereas dl -2, 4-diaminobutyric acid (5 × 10⁻³ M ) caused a sevenfold increase and β -alanine was inactive. The results indicate that glial uptake has little effect on GABA inactivation in the cerebral cortex. The inhibition of neuronal uptake seems a more effective tool to increase GABA concentration in the synaptic cleft, and consequently also in GABA output, than the inhibition of GABA metabolism.     

Interaction of piracetam with 3H-imipramine binding sites and the GAMA-benzodiazepine receptor complex of brain membranes

Piracetam at a concentration of 10(-6) M was shown to behave as a noncompetitive inhibitor of 3H-imipramine specific binding to rat brain membranes. At the same time piracetam failed to influence specific binding of 3H-mianserin to membranes of guinea-pig cerebellum, which is indicative of its inability to suppress histamine H1 receptors, a component of 3H-imipramine specific binding sites. At a concentration of 10(-4) M piracetam does not change specific binding of 3H-flunitrazepam to rat hippocampal membranes in the absence of GABA, but in the presence of 5 X 10(-5) M GABA, like atypical tranquilizer mebicar, acts as a competitor of 3H-flunitrasepam binding. Though Ro-15 1788 did not suppress anxyolytic piracetam (and mebicar) effect, our results give evidence of a possible involvement of GABA-benzodiazepine supramolecular complex in the anxiolytic activity of piracetam.     

Free-GABA levels in the cerebrospinal fluid of patients suffering from several neurological diseases Its potential use for the diagnosis of diseases which course with inflammation and tissular necrosis

Summary Free GABA levels were measured in the cerebrospinal fluid (CSF) of 74 neurological patients suffering from cerebral cysticercosis (n = 9), Parkinson's disease (n = 5), multiple sclerosis (n = 6), epilepsy (n = 24), meningeal tuberculosis (n = 6), viral encephalitis (n = 3), cerebrovascular disease (n = 8) and several kinds of dystonia (n = 5). A statistical significant four-fold elevation in free GABA levels was found in patients with cerebral cysticercosis. A non statistical significant two-fold increase in free GABA levels was also encountered in the CSF of patients affected by cerebrovascular disease and viral encephalitis. No changes in CSF free GABA levels were found in patients suffering from any of the other disorders. It is suggested that free GABA levels may be elevated in the CSF of patients suffering from neurological diseases which course with inflammation and tissular necrosis such as cerebral cysticercosis. Much work is needed however to establishd whether CSF free GABA levels can be used as a diagnostic tool in at least some type of these patients.     

乌灵菌粉水提物对MCAO小鼠海马结构及BDNF,GABA水平的影响

目的:探讨乌灵菌粉(xylaria nigripes,XN)水提物对脑缺血再灌注模型小鼠海马形态和高分子量神经丝蛋白(neurofilament high molecular weight,NF-H)表达以及脑源性神经营养因子(brain derived neurotrophic factor,BDNF)和γ氨基丁酸(γ-aminobutyric acid,GABA)的影响。方法:将32只昆明小鼠随机分为对照组(sham)、模型组(MCAO)和乌灵菌粉水提物低、高剂量组,即XN(L)和XN(H)。sham组进行假手术(皮肤切开,分离颈动脉),模型组(MCAO)及乌灵菌粉组进行大脑中动脉闭塞(middle cerebral artery occlusion,MCAO),sham组和MCAO组术后即刻腹腔注射生理盐水,乌灵菌粉组则注射不同剂量的乌灵菌粉水提物(0.3 g/kg和0.6 g/kg),术后24 h,通过尼氏染色、免疫组化染色和酶联免疫吸附实验(enzyme-linked immunosorbent assay,Elisa)分别观察海马结构和NF-H的表达情况以及BDNF和GABA水平。结果:(1)模型组小鼠海马出现大量的空洞样改变,细胞排列不整齐,XN(H)组空洞样改变减少;(2)模型组NF-H染色的积分光密度显著低于对照组和XN(H)组,差异具有统计学意义(P0.05);(3)Elisa检测显示,模型组海马BDNF和GABA水平显著低于对照组和XN(H)组,差异具有统计学意义(P0.01),而且模型组与XN(L)组的GABA水平之间也存在显著性差异(P0.05)。结论:乌灵菌粉水提物对MCAO模型小鼠海马结构具有保护作用,这一作用可能与其调节GABA和BDNF水平有关。     

吡拉西坦联合胞磷胆碱对急性脑梗死认知功能和神经功能的影响

目的:研究吡拉西坦联合胞磷胆碱对急性脑梗死认知功能和神经功能的影响。方法:选择2014年1月～2018年1月我院的150例急性脑梗死患者,随机分为两组。对照组采用吡拉西坦治疗,观察组采用吡拉西坦联合胞磷胆碱治疗。采用神经功能缺损程度(National Institutes of Health Stroke Scale,NIHSS)、析蒙特利尔认知评估量表(Montreal cognitive assessment scale,Mo CA)和日常生活能力(Activities of daily living,ADL)评分量表,比较两组治疗前后神经功能、认识功能和日常生活能力变化。结果:观察组基本治愈15例,显效30例,有效26例,无效4例,恶化1例,总有效率为94.67%,明显高于对照组(P0.05);治疗后,两组的ADL和Mo CA评分明显升高,神经功能缺损量表(National Institutes of Health Stroke Scale,NHISS)评分明显降低,且观察组的ADL、Mo CA和NHISS评分明显优于对照组(均P0.05);治疗后,两组的血清细胞凋亡蛋白酶-3(cysteinyl aspartate specific proteinase-3,Caspase-3)和低氧诱导因子-1α(Hypoxia-inducible factor 1α,HIF-1α)水平均明显降低,且观察组明显低于对照组(均P0.05);对照组发生干呕1例(1.33%),恶心2例(2.67%),头痛1例(1.33%),头晕1例(1.33%);观察组发生干呕1例(1.33%),恶心1例(1.33%),头痛1例(1.33%),出血1例(1.33%);两组无明显差异(P0.05)。结论:吡拉西坦联合胞磷胆碱能改善急性脑梗死的认知功能和神经功能,其机制可能与调节细胞诱导因子Caspase-3和HIF-1α的表达水平相关。     

Long-term results of implantation of bioengineered and drug-eluting stents in patients with coronary heart disease: comparative characteristics of predictors of poor prognosis

The purpose of the investigation was to study the morphological and clinical characteristics affecting the long-term prognosis after implantation of bioengineered and drug-eluting stents in patients with coronary heart disease (CHD). The investigation covered 2362 patients with CHD. Genous bioengineered stents were implanted in 316 patients; Cypher rapamycin-eluting stents were in 2046 patients. The independent poor factor for complications was discontinuation of antiaggregatory therapy due to surgical interventions of different types in the drug-eluting stent group and stenting of extensive stenoses in the bioengineered stent group.     

Participation of GABA in mediating the effects of ethanol in rats with differing susceptibility to the development of experimental alcoholism

The influence of ethanol and of GABA receptors blocker bicuculline on recovery cycles of primary response of the sensorimotor cortex was studied in rats with strong and weak inclination to development of experimental alcoholism. It is found that in rats of the first group, inhibition in the cerebral cortex was weakened in comparison with the rats of the second group. Ethanol in non-narcotic doses intensified the inhibitory processes and its effects could be prevented or suppressed by bicuculline. The conclusion is made about GABA participation in mediation of ethanol effects on inhibitory processes in the cerebral cortex.     

溶栓胶囊联合丁苯酞软胶囊对脑梗死恢复期患者血液流变学、脑血流动力学和神经因子的影响

摘要 目的：探讨溶栓胶囊联合丁苯酞软胶囊对脑梗死恢复期患者血液流变学、脑血流动力学和神经因子的影响。方法：选取2021年1月-2022年1月期间长治医学院附属和平医院收治的100例脑梗死恢复期患者,按照随机数字表法分为研究组（50例）和对照组（50例）,对照组接受丁苯酞软胶囊治疗,研究组接受溶栓胶囊联合丁苯酞软胶囊治疗。对比两组疗效、血液流变学、脑血流动力学、神经因子和不良反应发生情况。结果：研究组90.00%的临床总有效率高于对照组72.00%（P<0.05）。治疗20 d后,两组美国国立卫生院神经功能缺损评分（NIHSS）评分下降,Barthel指数（BI）评分升高,且研究组改善幅度大于对照组（P<0.05）。治疗20 d后,两组全血粘度、血浆粘度、血沉（ESR）、纤维蛋白原（FIB）和红细胞压积（HCT）均下降,且研究组低于对照组（P<0.05）。治疗20 d后,两组平均血流速度（Vm）升高,搏动指数（PI）及阻力指数（RI）均下降,且研究组改善幅度大于对照组（P<0.05）。治疗20 d后,两组神经元特异性烯醇化酶（NSE）下降,神经生长因子（NGF）、神经营养因子（BDNF）升高,且研究组改善幅度大于对照组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：溶栓胶囊联合丁苯酞软胶囊可有效改善脑梗死恢复期患者血液流变学、脑血流动力学,促进神经功能恢复,提高生活活动能力,效果显著。     

Bilobalide prevents reduction of gamma-aminobutyric acid levels and glutamic acid decarboxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus

We previously reported that bilobalide, a constituent of Ginkgo biloba L. leaves, protected mice against convulsions induced by 4-O-methylpyridoxine (MPN). To elucidate the mechanism of the anticonvulsant activity of bilobalide, this study examined the effect of bilobalide on MPN-induced changes in the levels of gamma-aminobutyric acid (GABA) and glutamate, and in the activity of glutamic acid decarboxylase (GAD) in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels and GAD activity in the hippocampus and cerebral cortex were significantly enhanced by bilobalide treatment (30 mg/kg, p.o., for 4 days) alone. MPN significantly decreased GABA levels and GAD activity in the three brain regions tested compared with those in the control. Pretreatment with bilobalide effectively suppressed the MPN-induced reduction in GABA levels and GAD activity in the hippocampus and cerebral cortex. On the other hand, there were no significant differences in the glutamate levels in the three regions despite various treatments. These results suggested that bilobalide prevents MPN-induced reduction in GABA levels through potentiation by bilobalide of GAD activity, and this effect of bilobalide contributes to its anticonvulsant effect against MPN-induced convulsions.     

穴位针灸联合泼尼松治疗无听力变化耳鸣疗效及对血清5-HT、GABA影响

摘要 目的：探讨穴位针灸联合泼尼松治疗无听力变化耳鸣的疗效及对血清5-羟色胺 （5-hydroxytryptamine,5-HT）、γ-氨基丁酸（Gamma-Amino-Butyric Acid,GABA）影响。方法：选取我院2016年1月~2020年1月所收治的160例无听力变化的耳鸣患者,将其随机分为研究组和对照组,每组患者80例,对照组患者采取波尼松治疗,研究组患者采取穴位针灸联合泼尼松治疗,对比不同治疗方式治疗无听力变化的耳鸣疗效、听力障碍分级以及对血清5-HT、GABA影响。结果：两组治疗前气导平均听阈水平、耳鸣程度对比无统计学差异（P＞0.05）,治疗后,研究组气导平均听阈水平、耳鸣程度降低程度较对照组明显（P＜0.05）;研究组的治疗有效率85.00 %明显高于对照组53.75 %（P＜0.05）;研究组的听力恢复正常的人数明显高于对照组（P＜0.05）;中度听力障碍人数对比无显著差异（P＞0.05）;研究组的轻度听力障碍人数明显低于对照组（P＜0.05）;两组治疗前各神经递质含量（5-HT、GABA）对比无统计学差异（P＞0.05）,研究组治疗后5-HT、GABA改善程度较对照组更加明显（P＜0.05）。结论：穴位针灸联合泼尼松治疗无听力变化耳鸣的疗效显著,可改善患者的听力、耳鸣,调节中枢性神经递质含量,疗效明显优于单独西医治疗。     

Pre and postoperative assessment of regional cerebral blood flow in hydrocephalus by 99mTc-hexamethyl-propylenamine oxime SPECT

Cerebrovascular changes resulting from hydrocephalus still remain to be investigated. It has been suggested that hydrocephalus distorts the large feeding arteries and that the collapse of capillaries results in decreased cerebral blood flow. This clinical study was designed to evaluate the effect of shunting on regional cerebral blood flow in patients with obstructive hydrocephalus of varying duration. Technetium-99m hexamethyl propyleamine oxime (99mTc-HMPAO) was used to measure the cerebral perfusion, semiquantitatively, since the pattern of its distribution in brain is somewhat similar to that of regional cerebral blood flow (rCBF), and the pre and postoperative semiquantitative rCBF values of each lobe were calculated. Fifteen patients (8 F, 7 M) underwent both CT and single photon emission tomography (SPECT) using 99mTc-HMPAO examination before and 1 week after shunting. Mean percentage of all lobes were calculated by subtracting the preoperative mean rCBF of all lobes from the corresponding postoperative values. The patients were classified into 3 groups according to the mean percentage of all lobes. Group A: showed a marked increase in mean cortical blood flow (+ 16.00 +/- 2.9%), group B: a moderate increase (11.27 +/- 4.8%), and in group C: there was the least improvement in mean cortical blood flow (+ 1.17 +/- 2.7%). The mean duration of hydrocephalus of group A, group B and group C was 5 +/- 0.5 weeks, 8 +/- 1 weeks and more than 12 weeks, respectively. Psychological testing and clinical observation of the daily activities of the patients postoperatively showed some correlation with increased rCBF and clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Content of dicarboxylic acids and GABA in normal suslik brain and under the effect of oxygen at higher pressure

The content of glutamic, asparaginic and gamma-aminobutyric (GABA) acids in norm and under hyperoxia was determined in different cerebral areas of susliks living in places at different heights above sea level. In susliks at a height of 1700-2000 m above sea level the content of glutamate aspartate and GABA lowers significantly as compared to that in susliks at a height of 500-600 m above sea level. Under the effect of oxygen 6 at. ga at the 22nd minute on the average there occur convulsions in susliks living both in high mountains and middle mountains. Acute oxygen poisoning is not accompanied by noticeable shifts in the content of free dicarboxylic amino acids in the studied cerebral areas of middle-mountain susliks and is characterized only by an increase of the GABA content in the cerebellum. In high-mountain susliks the content of glutamate under these conditions increases in great cerebral hemispheres, while the asparate content lowers in cerebral hemispheres and cerebellum. In the latter the drop in the content of GABA is statistically significant.     

The effect of GABA on in vitro binding of two novel non-benzodiazepines, PK 8165 and CGS 8216, to benzodiazepine receptors in the rat brain

The effect of gamma-aminobutyric acid (GABA) on the binding of PK 8165, a quinoline derivative, and CGS 8216, a pyrazoloquinoline, was assessed in two different regions of the rat brain. PK 8165, a compound with reported anxiolytic properties, inhibited [3H]-propyl beta-carboline-3-carboxylate labeled receptors in the cerebellum with an IC50 of 844 nM and 370 nM in the absence and presence of micro M GABA, respectively. GABA (100 micro M) was less effective in the cerebral cortex, decreasing the IC50 value from 280 to 197 nM. In saturation isotherm studies with [3H]-CGS 8216, a benzodiazepine receptor antagonist, GABA (100 micro M) induced a small but significant reduction in the apparent affinity of [3H]-CGS 8216 for benzodiazepine receptors in the cerebral cortex but the Bmax was unchanged.