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1.
Shafqat R. Chaudhry Ilana S. Lendvai Sajjad Muhammad Philipp Westhofen Johannes Kruppenbacher Lukas Scheef Henning Boecker Dirk Scheele Rene Hurlemann Thomas M. Kinfe 《Brain stimulation》2019,12(3):643-651
Objective
To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.Methods
This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.Results
No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p?<?0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p?>?0.05]. No severe device-/stimulation-related adverse events occurred.Conclusion
2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]. 相似文献2.
γ-干扰素对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的影响 总被引:1,自引:0,他引:1
为了研究γ-干扰素(IFNγ)对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的作用,采用免疫组织化学方法对胆碱能神经元的特异性标记酶-胆碱乙酰基转移酶(ChAT)进行染色,ChAT阳性细胞的数量反映了胆碱能神经元的数量,并用14C-乙酰CoA作底物来检测ChAT活性。结果显示,IFNγ处理过的实验组,ChAT阳性细胞数量显著增加,ChAT活性也增加,这种增加被大鼠抗小鼠IFNγ单克隆抗体(Ab-IFNγ)完全拮抗。采用流式细胞术对细胞周期进行分析,细胞周期及细胞百分率无明显改变。用MAP2标记神经细胞,神经细胞数基本未增加。以上结果提示:IFNγ不能促进基底前脑和隔区神经元增殖,胆碱能神经元表达增加不是因为神经元数目增加而是分化的结果。 相似文献
3.
Summary The effect of distension on adrenergic innervation was investigated in the rat urinary bladder. Bladders were distended for 3 h by forced diuresis and ballon obstruction, and specimens were taken from the bladder dome, body and neck for the demonstration of glyoxylic acid-induced fluorescence of catecholamines. Depletion of catecholamines started after 10 h and was almost complete after 2 days. The fluorescence had recovered part way after 5–7 days and was practically normal after 21 days. Small, intensely fluorescent (SIF) cells in the ganglia continued to leak catecholamines throughout the 21-day study period. The primary clinical success of distension therapy for the treatment of unstable bladder may be at least partly due to a reversible disturbance in the function of the adrenergic nerves, which have an excitatory alpha-adrenergic dominance in such cases, but the persistent leakage from SIF cells raises the question of whether distension causes prolonged disturbances in bladder function. 相似文献
4.
Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease. 总被引:13,自引:0,他引:13
Elliott J Mufson Shuang Y Ma John Dills Elizabeth J Cochran Sue Leurgans Joanne Wuu David A Bennett Syed Jaffar Michelle L Gilmor Alan I Levey Jeffrey H Kordower 《The Journal of comparative neurology》2002,443(2):136-153
The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD. 相似文献
5.
Acetylcholinesterase inhibitors may improve myelin integrity. 总被引:2,自引:0,他引:2
George Bartzokis 《Neuropsychopharmacology》2007,62(4):294-301
Recent clinical trials have revealed that cholinergic treatments are efficacious in a wide spectrum of neuropsychiatric disorders that span the entire human lifespan and include disorders without cholinergic deficits. Furthermore, some clinical and epidemiological data suggest that cholinergic treatments have disease modifying/preventive effects. It is proposed that these observations can be usefully understood in a myelin-centered model of the human brain. The model proposes that the human brain's extensive myelination is the central evolutionary change that defines our uniqueness as a species and our unique vulnerability to highly prevalent neuropsychiatric disorders. Within the framework of this model the clinical, biochemical, and epidemiologic data can be reinterpreted to suggest that nonsynaptic effects of cholinergic treatments on the process of myelination and myelin repair contributes to their mechanism of action and especially to their disease modifying/preventive effects. The ability to test the model in human populations with safe and noninvasive imaging technologies makes it possible to undertake novel clinical trial efforts directed at primary prevention of some of the most prevalent and devastating of human disorders. 相似文献
6.
1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence. 相似文献
7.
M. Yu. Stepanichev M. L. Libe I. A. Chernyshevskaya A. G. Moiseenok N. V. Gulyaeva 《Neurochemical Journal》2007,1(3):244-248
Administration of cholinotoxin etylcholine aziridinium (AF64A) into the brain selectively induces nonrever-sible cholinergic deficit. Wistar rats were injected intracerebroventricularly bilaterally with AF64A at doses of 1–3 nmol/ventricle. 28 days later the number of neurons survived was counted in dorsolateral, intermediate and medial groups of cells of the medial septum. AF64A induced a decrease in neuronal density and expression of cholineacetyl transferase at all doses used as well as in all regions studied. Brain sections were also stained for NADPH-diaphorase representing neuronal NO-synthase. Effects of AF64A on NADPH-diaphorase expression depended on the region studied. The number of NADPH-diaphorase-positive cells increased in the medial cellular group where more cholineacetly transferase-positive cells survived. In contrast, decrease in NADPH-diaphorase expression in the dorsolateral group of cells coincided with low level of cholineacetyltransferase-po-sitive neurons. The data presented suggest that in the AF64A-dependent model of neurodegeneration NO may play a neuroprotective function. 相似文献
8.
Jeffrey A. Gray Stephen N. Mitchell Michael H. Joseph Grigory A. Grigoryan Sharon Dawe Helen Hodges 《Drug development research》1994,31(1):3-17
Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc. 相似文献
9.
Nicotine has been found to improve memory performance in a variety of tests including the radial-arm maze. Nicotine may have effects mediated by promoting the release of dopamine. The present study was conducted to determine the interactions of nicotine with D1 and D2 agonists. Rats were acutely administered nicotine, the D1 agonist SKF 38393, and D2/D3 agonist quinpirole, and nicotine together with each of these agonists. Nicotine significantly improved choice accuracy in the radial-arm maze. The D1 agonist SKF 38393 significantly impaired choice accuracy. Nicotine was effective in reversing this effect. The D2/D3 agonist quinpirole showed a trend toward potentiating the improvement in choice accuracy caused by 0.2 mg/kg (0.43 μmol/kg) of nicotine. These data show that, as with the nicotinic antagonist mecamylamine, there are significant interactions of dopamine systems with nicotine effects. © 1994 Wiley-Liss, Inc. 相似文献
10.
中国人HNPCC家系的临床特征及M3胆碱能受体基因(A)8区突变检测 总被引:1,自引:1,他引:0
目的:分析中国人遗传性非息肉病性大肠癌(HNPCC)家系的临床特征并检测这些家系中M3胆碱能受体基因(A)8区的突变情况.方法:根据2003年4月杭州会议制定的中国人HNPCC家系标准收集HNPCC家系共15个,分析其临床特征;提取先证者的外周血基因组DNA,PCR扩增M3胆碱能受体基因第8外显子中一段长153 bp,包含有微卫星位点(A)8的基因片段,直接进行DNA测序.结果:15个家系共有恶性肿瘤患者55例,其中大肠癌患者41例,平均每个家系发生大肠癌2.73例,73%的大肠癌患者发病年龄<50岁,51%的病灶位于近端结肠,40%发生在直肠肛门,同时和异时多原发大肠癌总发生率为12%,2/3的家系属于Lynch Ⅱ型,共发生肠外恶性肿瘤14例(18个),其中胃癌最常见.15例先证者外周血中无1例检测到M3胆碱能受体基因(A)8区的突变.结论:M3胆碱能受体基因与中国人群中HPNCC的发病可能无密切关系.中国人HNPCC家系标准应在临床工作中推广应用,并进一步验证其合理性和科学性. 相似文献