气温骤降条件下炎性细胞因子、基因表达与卒中发病的关系

除受传统危险因素影响之外,卒中发病还与气温骤降有关.对绝大多数地区的研究发现,卒中与冷天气关系密切,后者通过多种机制影响卒中的发病,如血管调节机制的季节变化、血液成分的改变以及对感染因素的影响等.研究证实,炎症凶子在动脉粥样硬化和卒中发病中起着重要作用,而寒冷应激对卒中患者基凶表达产生的影响也町能起着重要作用.文章概述了气温骤降与卒中发病的关系和机制.     

大气颗粒物短期暴露对卒中发病风险影响的汇总分析

目的 探讨大气颗粒物(PM10和PM2.5)短期暴露对卒中发病风险的影响.方法 检索文献数据库,对符合纳入标准的有关大气颗粒物与卒中发病的文献进行汇总分析.结果 共纳入42篇文献.汇总分析显示,PM10每升高10 μg/m3,短期内卒中发病风险增高0.6％[优势比(oddsratio,OR) 1.006,95％可信区间(confidence mterval,CI)1.003 ～1.009];PM2.5每升高10 μg/m3,短期内卒中风险增高1.3％(OR1.013,95％ CI1.006 ～1.019).亚组分析显示,PM10暴露仅与缺血性卒中发病风险增高相关(OR 1.025,95％ CI1.010～1.041),PM25暴露仅与出血性卒中发病风险增高相关(OR1.031,95％ CI1.010～ 1.052).结论 短期内PM10和PM2.5浓度升高与卒中风险增高相关,PM25引起的卒中发病风险高于PM10.     

谷氨酸与缺血性卒中早期神经功能恶化

缺血性卒中早期神经功能恶化(early neurological deterioration,END)的机制尚不明确,也缺乏可靠的预测因素和有效的防治措施.谷氨酸介导的兴奋性毒性机制在缺血事件级联反应中发挥着很重要的作用.血浆谷氨酸水平增高是END的重要预测因素之一.研究表明,兴奋性氨基酸转运体-2基因启动子区多态性是个体对END易感性的潜在原因.一些拮抗谷氨酸能通路的治疗策略可作为干预END的策略.     

脑缺血时兴奋性氨基酸毒性

细胞外高浓度兴奋性氨基酸能导致细胞死亡。近来发现脑缺血时兴奋性氨基酸明显增高。文章对脑缺血时脑内兴奋性氨基酸及其受体作用特点，性氨基酸毒性机制以及有头脑了保护策略作一综述。     

脑缺血时兴奋性氨基酸毒性

细胞外高浓度兴奋性氨基酸能导致细胞死亡。近来发现脑缺血时兴奋性氨基酸明显增高。文章对脑缺血时脑内兴奋性氨基酸及其受体作用特点、兴奋性氨基酸毒性机制以及有关脑保护策略作一综述。     

缺血性卒中与兴奋性氨基酸研究的进展

急性卒中的进展常使死亡率和功能缺失增加。目前关于卒中进展的机制知之甚少,也没有脑梗死进展的良好预测指征。动物实验显示,兴奋性氨基酸是引起神经元死亡介质,与局灶性脑缺血恶化有关。在128例急性缺血性卒中病人前瞻性研究中,作者对血浆和脑脊液中谷氨酸和甘氨酸浓度与卒中早期进展的关系进行了研究。     

亚临床甲状腺功能减退症与缺血性卒中

亚临床甲状腺功能减退症（subclinicalhypothyroidism,SCH）可能与颈动脉粥样硬化、血脂异常、高血压、高同型半胱氨酸血症、冠心病之间存在关联,而这些因素常被视为缺血性卒中的危险因素。 SCH与卒中发病风险之间的相关性目前尚不清楚,SCH可增高卒中风险的假设未能得到证实,甚至有研究表明SCH可能对卒中预后产生有利影响。文章对SCH与卒中危险因素、卒中风险和预后的关系进行了综述。     

寒潮对缺血性脑卒中的影响及可能机制

<正> 脑卒中是中老年人的常见病,其与寒潮的关系越来越受到关注。有研究表明在寒冷季节,尤其是气温骤降的寒潮时,缺血性脑卒中发病明显增多。其机制尚未完全明确。我们将阐述寒潮导致缺血性脑卒中可能的机制及干预措施。1 寒潮对缺血性脑卒中的影响流行病学调查及临床观察均发现缺血性脑卒中的发病有一定的季节规律,冬季缺血性脑卒中的发病率较夏季明显增高,与冬季气温下降和寒潮来袭有关。Ebi等发现缺血性脑卒中除了年龄、性别以外还有地域性差异,主要由环境温度的变化所致。缺血性脑卒中的住院率与该地区环境温度变化剧烈程度呈正相关,与温度控制条件(如经济因素)呈负相关。在人工寒潮的动物实验中也发现寒潮组的脑卒中发病率较非寒潮组明显增高。     

急性卒中后谵妄

谵妄是急性卒中的一种常见并发症,通常提示患者转归不良、病死率较高、住院时间较长以及痴呆风险增高.因此,急性卒中后谵妄的早期发现和干预具有重要意义.文章从卒中后谵妄的发病机制、危险因素、诊断评估、治疗和转归等方面进行了综述.     

气象因素促发卒中的实验研究

目的 探讨气象因素对易卒中型肾血管性高血压大鼠（RHRSP）卒中发病的影响。方法 用Cox回归法分析卒中的发生与气压、最低气温、平均相对湿度等15个气象因素及平均血压的关系。结果 RHRSP组心、脑有不同和蔼的高血压性动脉硬化,有116只出现自发性卒中,并随0潮来临呈高峰发病,其中与平均气压、最低气漫画、温差和相对湿度有关（P＜0．05）,与其它的气象因素无显著相关（P＞0．05）。血压的变化与最低气温呈负相关（P＜0．01）,而与气压呈正相关（P＜0．05）。结论 RHRSP卒中的发生与天气的寒冷、气温的骤降、气压及平均相对湿度的上升有关。气象因素的预后指数方程有可能对高血压的卒中危险起一定的预报作用。     

Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated.

In the mammalian neostriatum, dopamine modulates neuronal responses mediated by activation of excitatory amino acid receptors. The direction of this modulation varies with the specific subtype of excitatory amino acid receptor activated. Responses evoked by iontophoretic application of glutamate (Glu) and the non-N-methyl-D-aspartate (NMDA) agonists quisqualate and alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid were significantly attenuated when dopamine was applied. In contrast, responses evoked by NMDA were markedly potentiated. The enhancement of NMDA-evoked excitations was mimicked by bath application of SKF 38393, a D1 receptor agonist. The D1 receptor antagonist SCH 23390 blocked the dopamine enhancement of NMDA-induced excitations. Quinpirole, a D2 receptor agonist, attenuated responses evoked by both NMDA and non-NMDA receptor agonists. These results indicate that the complex modulatory actions of dopamine in the neostriatum are a function of the excitatory amino acid receptor as well as the specific dopamine receptor subtype activated. These findings are of clinical relevance since the actions of dopamine and excitatory amino acids have been implicated in neurological and affective disorders.     

Excitotoxicity,energy metabolism and neurodegeneration

Summary There is increasing evidence that the neurotoxic effects of excitatory amino acids and their analogues are part of the pathogenesis of neuronal degeneration in acute and chronic neurological disease. Recent studies indicate that activation of excitatory amino acid receptors is also induced in the mechanism of neuronal damage induced by impairment of cellular energy metabolism. This article briefly summarizes the evidence for the presence of such a mechanism and discusses metabolic diseases in which excitatory amino acids alone or in combination with energy deficiency could play a pathogenetic role. In these and other metabolic diseases, antagonists to excitatory amino acid receptors may offer a therapeutic opportunity; however, there are potential limits that may prevent chronic use.     

Excitatory Amino Acid Receptors in the Paraventricular Hypothalamic Nucleus Mediate Pressor Response Induced by Carotid Body Chemoreceptor Stimulation in Rats

In urethane-anesthetized rats with spinal transection, antagonists of excitatory amino acid receptors, P2 purinoceptors and adrenoceptors were microinjected into the paraventricular hypothalamic nucleus (PVN) and their effects on the pressor response evoked by carotid body chemoreceptor stimulation were examined. Microinjections of the non-selective excitatory amino acid antagonist kynurenate, the non-NMDA receptor antagonist CNQX and the NMDA antagonist 2-     

Excitatory amino acid uptake and N-methyl-D-aspartate-mediated secretion in a neural cell line.

A functional N-methyl-D-aspartate (NMDA) receptor has been identified on HT-4 cells, a clonal neural cell line, in which glutamate activates the receptor to elicit neurotransmitter secretion. Specific inhibitors of the NMDA receptor block glutamate-mediated secretion, and the characteristics of NMDA-mediated secretion parallel the reported properties of the NMDA receptor. Excitatory amino acid secretion can be elicited by potassium-evoked depolarization and is not the simple reversal of the uptake system. 2-Amino-4-phosphonobutyrate (APB) inhibits depolarization-induced secretion of excitatory amino acids but has no effect on excitatory amino acid uptake, suggesting that the APB binding protein in the brain represents a component involved in the secretion of excitatory amino acids.     

Compartmentalization of excitatory amino acid receptors in human striatum.

Division of the mammalian neostriatum into two intermingled compartments called striosomes and matrix has been established by analysis of enzyme activity, neuropeptide distribution, nucleic acid hybridization, and neurotransmitter receptor binding. Striosomes and matrix are distinct with respect to afferent and efferent connections, and these regions provide the potential for modulation and integration of information flow within basal ganglia circuitry. The primary neurotransmitters of corticostriatal afferents are excitatory amino acids, but to date no correlation of excitatory amino acid receptors and striatal compartments has been described. We examined binding to the three pharmacologically distinct ionotropic excitatory amino acid receptors, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainate, in human striatum using in vitro receptor autoradiography and compared the binding to striosomes and matrix histochemically defined by acetylcholinesterase activity. Our findings reveal increased binding to N-methyl-D-aspartate receptors and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in matrix relative to striosomes and increased kainate receptor binding in striosomes relative to matrix. These results suggest that afferent input to the two striatal compartments may be mediated by pharmacologically distinct excitatory amino acid receptor subtypes.     

New Developments in the Pharmacotherapy of Alcohol Dependence

Neuroscientific underpinnings and pharmacotherapeutic treatments of sub‐stance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. New data on opiate antagonists and acamprosate, an agent that exerts actions through excitatory amino acid systems in relapse prevention, will be reviewed. Finally, there will be a review of new data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy.     

Endogenous excitatory amino acid regulation of the progesterone-induced LH and FSH surge in estrogen-primed ovariectomized rats.

The role of endogenous excitatory amino acid neurotransmission in the regulation of progesterone and triamcinolone acetonide-induced LH and FSH release was examined. Estrogen-primed ovariectomized rats were utilized in this study. Progesterone or triamcinolone acetonide (1 mg/kg body weight) treatment led to a highly significant elevation of serum LH and FSH levels 5 h later. Treatment with the selective noncompetitive NMDA receptor antagonist, MK801, had no effect on serum LH and FSH levels when compared to estrogen controls. However, MK801 administered 1 h prior to progesterone or triamcinolone acetonide administration completely blocked their ability to induce LH and FSH surges. These studies demonstrate for the first time the involvement of endogenous excitatory amino acid neurotransmission in the mediation of progesterone and corticosteroid-induced LH and FSH surges.     

Distinct pharmacological properties of excitatory amino acid receptors in the rat striatum: study by Na+ efflux assay.

Specific 22Na+ efflux rates from preloaded rat striatal slices are increased in a dose-dependent manner by L-glutamate and other excitatory amino acids displaying the following order of efficiency: N-methyl-D-aspartate greater than DL-homocysteate greater than quisqualate greater than kainate greater than D-glutamate greater than L-glutamate greater than L-aspartate. Amino acid antagonists such as 2-amino-5-phosphonovalerate, gamma-D-glutamylglycine, DL-aminosuberate, DL-aminoadipate, and diethyl glutamate but not nonexcitatory amino acids such as gamma-aminobutyric acid inhibit the amino acid-induced increase in specific 22Na+ efflux rate. Increased K+ concentrations, in the presence of 2 mM Ca2+, increase the specific 22Na+ efflux. The latter and the response to N-methyl-D-aspartate, but not the responses to L-glutamate, L-aspartate, quisqualate, and kainate, are inhibited to similar extents by the same antagonists. These results suggest the release from striatal nerve terminals of a putative neurotransmitter with pharmacological properties different from those of L-glutamate or L-aspartate but similar to those of N-methyl-D-aspartate. The results of this study show that the stimulation of the 22Na+ efflux in brain slices by neuroactive amino acids and K+ ions is a valid and powerful tool for pharmacological investigations of excitatory amino acid receptors and their putative ligands.     

Distinct muscarinic receptors inhibit release of gamma-aminobutyric acid and excitatory amino acids in mammalian brain.

Intracellular recordings were made from neurons of rat lateral amygdala, nucleus accumbens, and striatum in vitro. Synaptic potentials mediated by gamma-aminobutyric acid and by excitatory amino acids were isolated pharmacologically by using receptor antagonists, and their amplitudes were used as a measure of transmitter release. Muscarine and acetylcholine inhibited the release of both gamma-aminobutyric acid and excitatory amino acids, but measurements of the dissociation equilibrium constants for the antagonists pirenzepine, 11-(2-[(diethylamino)methyl]-1-piperidinyl)acetyl-5,11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepine-6-one, methoctramine, and hexahydrosiladifenidol indicated clearly that different muscarinic receptors were involved (M1 and probably M3, respectively). The differential localization of distinct muscarinic receptor subtypes on terminals releasing the major inhibitory and excitatory transmitters of the brain could be exploited therapeutically in some movement disorders and Alzheimer disease.     

Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods

Background: Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals. Methods: In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high‐performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate. Results: An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels. Conclusion: The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate.