托吡酯对缺血性脑损伤的神经保护作用

缺血性脑损害的病理生理机制涉及许多方面。最近的动物实验发现,抗癫药托吡酯具有一定的神经保护作用,可通过多种途径减轻缺血性神经元损伤,并且具有良好的耐受性和血脑屏障通透性,有望作为一种有效的神经保护药应用于临床。     

脑缺血半暗带的病理损伤机制与干预对策

文章综述了脑缺血半暗带病理损伤机制与缺血性卒中治疗干预对策的主要进展，并对溶栓药与神经保护药联合应用在缺血性卒中的潜在临床价值进行了评述。     

缺血性卒中的神经保护药:现状与挑战

作为缺血性卒中的一种治疗策略,神经保护药被用于拮抗脑缺血时的一系列有害分子生物学事件.文章综述了神经保护药治疗急性缺血性卒中的现状,以及从临床前研究证据向临床试验转化所面临的挑战.应将血管内皮细胞-胶质细胞-神经元作为一个整体进行研究.     

脑缺血半暗带的病理损伤机制与干预对策

文章综述了脑缺血半暗带病理损伤机制与缺血性卒中治疗干预对策的主要进展,并对溶栓药与神经保护药联合应用在缺血性卒中的潜在临床价值进行了评述。     

雌激素对缺血性卒中的神经保护作用机制

大量临床研究和动物实验均表明，雌激素对卒中具有神经保护作用，其机制相当复杂，涉及多个方面。文章就近年来雌激素对缺血性卒中的神经保护作用机制的研究进行了综述。     

缺血性卒中神经保护药物的临床前和临床研究分析及进展

缺血性脑损伤(卒中)的研究始于20世纪70年代,在早期,通过对卒中发病机制和调节介质的研究,提示神经保护药是潜在、有效的干预和治疗药物。此后,大量研究采用动物模型来探讨缺血后脑内生化和分子生物学的改变,证实部分药物确实具有一定神经保护作用,为神经保护药物在临床中的应用提供了依据。通过MEDLINE检索引擎(PubMed)以"neuropro-     

神经保护药治疗急性缺血性卒中:有效还是无效?

尽管动物实验显示神经保护药治疗缺血性卒中有效,但是临床试验却未能重现动物实验的结果.这导致人们开始怀疑这种治疗是否对急性缺血性卒中确实有效.文章概述了相关的争论.     

毛柳甙对缺血性卒中保护作用机制的研究进展

<正>毛柳甙是红景天根茎中的重要药理成分,具有抗衰老、防辐射、抗肿瘤、心血管保护、调节免疫等广泛的药理活性~([1-3])。研究显示,毛柳甙具有神经保护作用,有望用于缺血性卒中的治疗~([4])。笔者就毛柳甙对缺血性卒中的神经保护作用机制进行综述。     

急性缺血性卒中的血管内低温治疗

大量动物实验和临床研究表明，血管内低温对缺血性卒中具有神经保护作用。文章从作用机制、临床研究、影响治疗结果的因素以及并发症的防治等方面对缺血性卒中的血管内低温治疗进行了综述。     

促红细胞生成素对脑损伤的保护作用

促红细胞生成素(EPO)具有神经保护作用，在缺血性脑损伤和蛛网膜下腔出血等中枢神经系统损伤中发挥保护作用的机制有多种，如抗细胞凋亡和清除自由基等。此外，EPO能通过与特异性受体结合透过血脑屏障，这是许多神经营养因子所不具备的优势。因此，其临床应用前景看好。     

Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic peptide with recently identified neurotrophic effects. Because some neurotrophic factors can protect neurons from hypoxic or ischemic injury, we investigated the possibility that VEGF has similar neuroprotective properties. In HN33, an immortalized hippocampal neuronal cell line, VEGF reduced cell death associated with an in vitro model of cerebral ischemia: at a maximally effective concentration of 50 ng/ml, VEGF approximately doubled the number of cells surviving after 24 h of hypoxia and glucose deprivation. To investigate the mechanism of neuroprotection by VEGF, the expression of known target receptors for VEGF was measured by Western blotting, which showed that HN33 cells expressed VEGFR-2 receptors and neuropilin-1, but not VEGFR-1 receptors. The neuropilin-1 ligand placenta growth factor-2 failed to reproduce the protective effect of VEGF, pointing to VEGFR-2 as the site of VEGF's neuroprotective action. Two phosphatidylinositol 3'-kinase inhibitors, wortmannin and LY294002, reversed the neuroprotective effect of VEGF, implicating the phosphatidylinositol 3'-kinase/Akt signal transduction system in VEGF-mediated neuroprotection. VEGF also protected primary cultures of rat cerebral cortical neurons from hypoxia and glucose deprivation. We conclude that in addition to its known role as an angiogenic factor, VEGF may exert a direct neuroprotective effect in hypoxic-ischemic injury.     

Melatonin and ischemia-reperfusion injury of the brain

Abstract:  This review summarizes the reports that have documented the neuroprotective effects of melatonin against ischemia/reperfusion brain injury. The studies were carried out on several species, using models of acute focal or global cerebral ischemia under different treatment schedules. The neuroprotective actions of melatonin were observed during critical evolving periods for cell processes of immediate or delayed neuronal death and brain injury, early after the ischemia/reperfusion episode. Late neural phenomena accounting either for brain damage or neuronal repair, plasticity and functional recovery taking place after ischemia/reperfusion have been rarely examined for the protective actions of melatonin. Special attention has been paid to the advantageous characteristics of melatonin as a neuroprotective drug: bioavailability into brain cells and cellular organelles targeted by morpho-functional derangement; effectiveness in exerting several neuroprotective actions, which can be amplified and prolonged by its metabolites, through direct and indirect antioxidant activity; prevention and reversal of mitochondrial malfunction, reducing inflammation, derangement of cytoskeleton organization, and pro-apoptotic cell signaling; lack of interference with thrombolytic and neuroprotective actions of other drugs; and an adequate safety profile. Thus, the immediate results of melatonin actions in reducing infarct volume, necrotic and apoptotic neuronal death, neurologic deficits, and in increasing the number of surviving neurons, may improve brain tissue preservation. The potential use of melatonin as a neuroprotective drug in clinical trials aimed to improve the outcome of patients suffering acute focal or global cerebral ischemia should be seriously considered.     

Stellenwert und Perspektive des Edelgases Xenon in Intensiv- und Notfallmedizin

The use of the noble gas xenon has been proven to be feasible and safe in animal studies as well as in the clinical setting. In addition to its desirable pharmacokinetic profile, xenon offers remarkable hemodynamic stability and potential cardio- and neuroprotective effects. However, its adoption into routine anesthesia has been limited due to its high cost and the lack of available equipment for its application. This paper reviews current clinical experience with xenon as an anesthesic, points out currently existing limitations for its clinical application and gives an outlook on further developments, particularly its potential role as a neuroprotective agent in special intensive care scenarios such as hypoxic brain injury after cardiopulmonary resuscitation.     

自由基清除剂依达拉奉对脑缺血的治疗作用

自由基在各种缺血性损伤中起重要作用。自由基清除剂依达拉奉打破了神经保护治疗无效的悲观现状。动物实验和临床试验表明 ,依达拉奉在治疗缺血再灌注损伤中的有效。     

米诺环素对缺血性卒中的神经保护作用

米诺环素为第2代半合成四环素类抗生素,多种动物实验模型和临床试验表明其具有神经保护作用,其机制与抑制凋亡、减轻炎性反应、缩小梗死体积和减轻血管损伤有关.文章对急性缺血性卒中临床前期和早期临床试验中米诺环素的神经保护作用进行了综述.     

Effects of topiramate on ethanol and saccharin consumption and preferences in C57BL/6J mice

BACKGROUND: Topiramate has recently been found to be more effective than placebo as an adjunct treatment for alcohol dependence, but it has not yet been investigated in animal models of ethanol consumption. The current experiment examined the effects of topiramate on ethanol drinking in mice using a continuous access, two-bottle choice procedure. METHOD: C57BL/6J male mice were offered a 10% v/v ethanol solution versus tap water over 4 consecutive days per week. Mice were assigned to topiramate (1-50 mg/kg) or saline groups and received injections before the beginning of the dark phase of the light cycle. Topiramate dose increased over 5 successive weeks (1, 5, 10, 25, and 50 mg/kg). Fluid intake was measured 2, 4, and 23 hr after injection. Body weight and food intake were measured at the time of injection. In a second phase, mice were offered saccharin solutions (0.2 and 2.5% w/v) versus tap water after topiramate (50 mg/kg) or saline injections. RESULTS: Results revealed that high topiramate doses (25 and 50 mg/kg) increased water intake and decreased ethanol preference. Compared with saline controls, topiramate produced dose-dependent, bidirectional effects on ethanol dose, with 25 mg/kg of topiramate increasing ethanol dose at 4 and 23 hr after injection but 50 mg/kg topiramate decreasing ethanol dose at 2 hr after injection. During saccharin exposure, topiramate decreased saccharin preference (for 2.5% w/v saccharin solution) and marginally increased water intake but did not directly alter intake of the saccharin solutions. Topiramate had no effects on body weight or daily food intakes. CONCLUSIONS: Topiramate reduced ethanol preference in C57BL/6J mice, but this effect was primarily attributable to elevated water intake. Topiramate also reduced saccharin preference, likely through marginally significant increases in water intake. Increases in water intake and bidirectional effects of topiramate on ethanol dose complicate conclusions with regard to the effects of topiramate on ethanol reward.     

Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: a randomized controlled trial

BACKGROUND: Previously, our group has shown that topiramate, a sulfamate-substituted fructopyranose derivative, is an effective treatment for alcohol dependence. Herein, we extend that proof-of-concept study by determining whether cigarette-smoking, alcohol-dependent individuals from the earlier study also experienced improved smoking outcomes. METHODS: As a subgroup analysis of a larger double-blind, randomized, controlled, 12-week study comparing topiramate vs placebo as treatment for alcohol dependence, a 12-week clinical trial compared topiramate vs placebo in 94 cigarette-smoking, alcohol-dependent individuals. Of these, 45 were assigned to receive topiramate (escalating dose from 25 to 300 mg/d) and the remaining 49 had placebo as an adjunct to weekly standardized medication compliance management. The primary outcome was smoking cessation ascertained by self-report and confirmed by the level of serum cotinine (nicotine's major metabolite). RESULTS: Topiramate recipients were significantly more likely than placebo recipients to abstain from smoking (odds ratio, 4.46; 95% confidence interval, 1.08-18.39; P = .04). Using a serum cotinine level of 28 ng/mL or lower to segregate nonsmokers from smokers, we found that the topiramate group had 4.97 times the odds of being nonsmokers (95% confidence interval, 1.1-23.4;P = .04). Smoking cessation rates for topiramate recipients were 19.4% and 16.7% at weeks 9 and 12, respectively, compared with 6.9% at both time points for placebo recipients. CONCLUSION: In this trial, topiramate (up to 300 mg/d) showed potential as a safe and promising medication for the treatment of cigarette smoking in alcohol-dependent individuals.     

Topiramate does not affect the acquisition or expression of ethanol conditioned place preference in DBA/2J or C57BL/6J mice

BACKGROUND: Topiramate, an anticonvulsant, has been reported to increase the number of abstinent days and decrease craving in alcohol-dependent individuals. However, the neurobiological basis for topiramate's effect is unknown. To assess topiramate's effect on ethanol's rewarding and conditioning rewarding effects, the present experiments examined the effects of topiramate on the acquisition and expression of ethanol-induced conditioned place preference (CPP) in DBA/2J and C57BL/6J mice. METHODS: A biased apparatus and subject assignment were used. Mice received ethanol (2 g/kg) or saline paired with an initially nonpreferred floor (CS+) and saline paired with an initially preferred floor (CS-) for 5-minute conditioning trials. During the acquisition experiments, mice received a pretreatment of topiramate (0, 5, 10, 20, 50, or 100 mg/kg) 1 hour before the CS+ trials. On intervening CS- trials, mice received a pretreatment of saline. For the preference test, all mice received saline injections and were placed on a split floor for a 30-minute test. During the expression experiments, mice received no drug pretreatment on conditioning trials, but were pretreated with topiramate (0, 10, 50, or 100 mg/kg) 1 hour before the test session. RESULTS: Ethanol-induced CPP was observed in both strains, but topiramate did not affect the acquisition or expression of ethanol-induced CPP in either strain. Despite its failure to alter CPP, topiramate produced dose-dependent locomotor activating effects in both strains. These effects were observed both in the presence and in the absence of ethanol. CONCLUSIONS: These findings indicate that topiramate has no effect on ethanol's rewarding or conditioned rewarding effects as indexed by the place conditioning procedure. Thus, these studies raise the possibility that topiramate's efficacy in the treatment of alcoholism results from its impact on brain areas other than those that mediate ethanol's rewarding or conditioned rewarding effects. One alternative possibility is that topiramate decreases withdrawal-induced negative affective states that normally contribute to relapse.     

Protective effect of melatonin in a model of traumatic brain injury in mice

ABSTRACT: The pineal hormone melatonin has recently been shown to exert neuroprotective activity in a variety of experimental neuropathologies in which free radicals are involved. This neuroprotective effect has been attributed to the antioxidant properties of melatonin. Considering that free radicals also play a deleterious role in traumatic brain injury (TBI), the purpose of the present study was to determine whether melatonin would have a beneficial effect in this pathology. Head injury was induced in mice and the neurological deficit was evaluated at 24 hr by a grip test. In this model, the free radical scavenger, α-phenyl-tert-butyl-nitrone (2 ± 100 mg/ kg, i.p.) given 5 min and repeated at 4 hr after TBI was neuroprotective. Melatonin (1.25 mg/kg, i.p.) given 5 min and repeated at 1,2, and 3 hr after head trauma also significantly reduced the neurological deficit. This beneficial effect was not due to melatonin-induced hypothermia since repeated treatment with melatonin did not modify the colonic temperature of mice. This study shows that melatonin exerts a beneficial effect on the neurological deficit induced by traumatic brain injury in mice. The mechanisms of this neuroprotection remains to be established, and more particularly, the contribution of the antioxidant activity of melatonin.