迷走神经刺激对戊四氮致痫大鼠丘脑网状核NMDAR1 mRNA和GABAARα1 mRNA的影响

为探讨迷走神经刺激（Vagus nerve stimulation,VNS)抗癫痫的作用机制。应用原位杂交组织化学及图像分析方法研究戊四氮（Pentylenetetrazol,PTZ)致痫大鼠丘脑网状核谷氨酸受体NMDAR1mRNA和γ-氨基丁酸A受体（GABAAR）α1亚单位mRNA的变化。结果显示，PTZ致痫组大鼠丘脑网状核NMDAR1mRNA表达明显高于正常对照组，而VNS抗癫痫组明显低于PTZ致癫痫组，与之相反，PTZ致癫痫组GABAARα1mRNA的表达明显低于正常对照组，VNS抗癫痫组明显高于PTZ致癫痫组，上述结果表明，VNS可能通过抑制丘脑网状核兴奋的神经递质受体NM-DAR的活动和增强抑制性神经递质受体γ-氨基丁酸受体GABAAR的活动，降低大脑皮层的兴奋性，抑制癫痫的发生和发展。     

蓝斑核的升压效应以及在孤束核水平对迷走神经传入的调制作用

55只家兔身上应用电刺激和微量注射谷氨酸钠的方法观察了蓝斑核在心血管调节中的作用,并采用记录细胞电活动的方法了解了蓝斑核和孤束核的关系。结果表明:电刺激或化学兴奋蓝斑核均引起动脉血压升高和交感神经传出活动增强,并削弱刺激颈迷走神经中枢端所引起的血压变化(升高或降低)和交感神经     

颈部迷走神经干刺激对癫痫大鼠脑内Fos样表达的影响

目的 研究颈部迷走神经干刺激（VNS）抑制癫痫发作上传通路过程中的关键核团及相关脑区。方法 利用红藻氨酸（KA）诱发大鼠复杂部分性癫痫发作。并结合Fos免疫组织化学方法观察左颈部迷走神经干电刺激后全脑及延髓内Fos的分布及电刺激的影响。结果 VNS后脑干双侧孤束核、蓝斑、臂旁核、中脑导水管周围灰质有很强的特异性Fos表达，外侧缰核、丘脑室旁核、菱形核、下丘脑室旁核、杏仁中央核、终纹床核、隔外侧核、梨状皮质等脑区亦可见Fos阳性细胞。预先给予电刺激后海马、齿状回、额、顶、颞皮质区域Fos表达明显受到抑制。结论 VNS后Fos阳性的脑区及核团可能是电刺激发挥抑痫作用的关键部位，其神经元活性的改变或递质调节可能间接或直接影响大脑皮质的功能。     

大鼠迷走神经刺激的启动时间与抗痫效果

目前迷走神经刺激术 (vagusnervestimulation ,VNS)在临床应用中存在的主要问题是怎样实施才能最大限度地发挥其应有的作用。为此 ,我们用海人藻酸复制大鼠癫痫模型 ,以ECoG、行为学表现为观测指标 ,探讨VNS的启动时间是否与癫痫治疗的效果有关。1　材料和方法1 1　动物及分组 :Wistar大鼠 34只 ,腹腔注射 3%戊巴比妥钠 (4 0mg/Kg) ,刺激电极安放在左侧迷走神经干 ,利用银球电极记录ECoG。颈部皮下注射海人藻酸 (10mg/kg体重 )致痫。实验动物随机分为 (1)海人藻酸致痫组 (KA组 ) ;(2 )痫性发作前先行VNS组 (VNS +KA组 ) ;(3)痫性…     

味觉刺激与内脏刺激对大鼠孤束核FOS表达的影响

为研究内脏不适刺激和甜味刺激在脑干孤束核的相互作用 ,本研究应用免疫组织化学方法观察了先后联合给予胃内灌注 Li Cl和口内灌注糖精对大鼠孤束核吻尾不同部位的 FOS表达变化的影响。结果发现 ,胃内 L i Cl刺激和口内糖精刺激及两者联合刺激后 ,大鼠孤束核吻尾方向不同部位的 F OS表达增加。析因分析表明 ,两者先后联合刺激对孤束核内 FOS表达在尾侧最后区周围的内脏亚核和吻侧的味觉亚核有交互作用 ,提示甜味觉刺激和不适内脏刺激在孤束核的这些部位可以相互减弱对方的作用     

孤束核与延鼠尾端腹外侧区微量注射GABA对交感传出活动的影响

本文观察了在家兔孤束核(NTS)与延髓尾端腹外侧区(CVL)微量注射GABA对电刺激上述区域时所诱发的肾交感传出放电(SND)和血压变化的影响。结果表明:(1)在NTS内微量注射GABA,未见肾交感自发放电有明显变化。注射后,刺激NTS诱发的肾交感神经传出放电(NTS—     

迷走神经电刺激对大鼠肠缺血再灌注后肠损伤的影响

目的:观察迷走神经电刺激对大鼠肠缺血再灌注（I/R）后肠损伤的影响。 方法:30只雄性Wistar大鼠，双侧颈迷走神经切断后，随机分为3组（n=10）：（1）肠缺血再灌注（I/R）组：暴露腹腔后夹闭肠系膜上动脉（SMA）1 h，开放再灌注2 h；（2）迷走神经刺激（VNS）组：在夹闭前及再灌注开始均以5 V、2 ms和1 Hz强度的电能持续刺激左颈部迷走神经远端20 min；（3）假手术对照(SC)组：仅暴露腹腔，不行SMA夹闭及电刺激。颈动脉插管监测平均动脉压（MAP）。所有动物在再灌注2 h后处死，取小肠组织行光学、电子显微镜观察肠粘膜损伤程度并行改良的Chiu’s评分；检测血浆丙二醛（MDA）、肿瘤坏死因子（TNFα）含量。 结果:各组大鼠MAP在缺血期基本保持平稳。而在再灌注期，I/R组的MAP随时间延长明显低于SC组（P＜0.05），而VNS组能明显拮抗MAP下降（P＜0.05）。光学、电子显微镜观察显示I/R后肠组织出现不同程度的损伤，I/R组最为严重，而VNS组相对较轻；但两组的改良Chiu’s评分值显著高于SC组（P＜0.01），VNS组的评分值明显低于I/R组（P＜0.01）。I/R组血浆MDA、TNFα含量明显高于SC组和VNS组（P＜0.05，P＜0.01）；VNS组血浆MDA含量高于SC组（P＜0.05），VNS组血浆TNFα与SC组无显著差异（P＞0.05）。 结论:电刺激迷走神经能显著减轻I/R肠粘膜结构的病理改变并使再灌注期的循环血压得到一定改善，其保护效应可能与减少脂质过氧化、下调TNFα生成有关。     

2.104 c-fos在电针调控胃运动中的表达及其意义

目的探讨原癌基因c-fos在穴位电针对胃运动影响中的表达及其意义 .方法采用免疫组织化学方法及电生理的方法,观察电针刺激足三里等不同穴位,c-fos在中枢延髓的孤束核(NTS)及迷走神经背运动核(DMV)中的表达,同时采用浆膜法检测胃电变化情况.结果电针刺激足三里等不同穴位c-fos在中枢延髓的孤束核(NTS)及迷走神经背运动核(DMV)中的表达情况不同,且胃电也发生较为明显的变化.结论穴位电针对胃运动具有调节作用.以c-fos的表达作为激活标志 ,提示这种调节作用可能是通过对中枢延髓孤束核(NTS)及迷走神经背运动核(DMV)神经元的激活而实现的.     

停止迷走神经刺激术后2年内7例癫癎患者的临床与EEG分析

目的：总结迷走神经刺激术(VNS)对顽固性癫痫的疗效及评价其临床应用的价值。方法：用VNS治疗7例顽固性癫痫患者，治疗期为3年，结束治疗后继续观察2年，共观察5年。整个观察期内患者仍用足量抗癫痫药物。比较治疗前、治疗期及结束治疗后癫痫的发作情况及EEG变化。结果：7例患者在VNS治疗期内5例有效，其中3例发作频率减少25％～50％，2例终止发作，另2例无效。结束VNS治疗后原有效的3例中，2例发作加重，1例发作类型改变，发作次数增加，但强度减轻；2例终止发作者中1例目前仍未发作，另1例癫痫复发。EEG情况与临床相一致，当癫痫发作被控制时，EEG明显好转，棘(尖)慢复合波减少。癫痫复发时EEG会出现相应的痫样放电。7例患者在结束随访的第五年，有6例EEG仍明显异常，有棘(尖)或棘(尖)慢复合波。结论：VNS治疗顽固性癫痫具有安全性，且治疗期间有一定的疗效，但由于其对发作的完全控制率低，停止刺激后易复发，且费用昂贵，很难作为一种令人满意的治疗方法。     

膈下迷走神经切断对条件性味觉厌恶大鼠脑内Fos表达的影响

目的:探讨膈下迷走神经切断与条件性味觉厌恶(CTA)对大鼠脑内Fos表达的影响及其交互作用.方法:将雄性SD大鼠随机分为CTA迷走神经切断组、CTA假手术组、正常迷走神经切断组和正常假手术组,对各组大鼠施予口腔插管手术,向2个CTA组大鼠口腔内给以蔗糖溶液联合腹腔注射使其获得CTA,于膈下切断迷走神经,然后进行免疫组织化学反应.结果:建立CTA使中缝苍白核(RPa)内Fos表达水平升高,且与切断迷走神经无关；建立CTA和迷走神经切断均可使孤束核内侧部(SolM) Fos表达水平升高；迷走神经切断使臂旁核中央外侧亚核(cls)内Fos表达水平升高,但与CTA无关；CTA与迷走神经切断对SolM和cls内Fos表达水平存在交互作用,迷走神经切断使对照组大鼠的Fos表达水平升高,但对获得CTA大鼠无影响.结论:大鼠获得CTA后,条件性味觉刺激可诱导RPa和SolM内Fos表达水平升高,且不依赖于迷走神经传人.     

Somatosensory and hypothalamic inhibitions of baroreflex vagal bradycardia in rats

Somatosensory and forebrain mechanisms inhibiting arterial baroreflexes were investigated in chloraloseurethane anesthetized and artificially ventilated rats. Electrical stimulation of the sciatic nerve (ScN) and the hypothalamic pressor area (HP) suppressed baroreflex vagal bradycardia (BVB) and hypotension provoked by electrical stimulation of the aortic depressor nerve (ADN). Suppression of BVB was more marked, but inhibitory potencies of ScN and HP were not different. These two inhibitions were considered to have a functional implication in common, since both were accompanied by increase in hindlimb vascular conductance. A variety of experiments were conducted to localize the target site of ScN and HP inhibitions of BVB. Either ScN or HP stimulations was without effect on antidromic compound spike potentials along ADN evoked by microstimulation of the nucleus tractus solitarius (NTS), precluding the possibility of these inhibitions being presynaptic. Both ScN and HP stimulation suppressed ADN-induced field potentials in the NA region which provoked vagal bradycardia upon microstimulation, but failed to affect ADN-induced responses, either field or unitary, in the NTS region. Antidromic unitary responses in the NA region to vagus cardiac branch stimulation were suppressed by ScN and HP stimulations in NTS-lesioned rats. Intracisternal bicuculline, a GABA antagonist, was found to abolish both ScN and HP inhibitions of BVB, while intracisternal muscimol, a GABA agonist, eliminated bradycardia. These findings suggest that somatosensory and forebrain inhibitions of BVB occur principally at the preganglionic cell level and are probably mediated by a GABAergic mechanism.     

The influence of vagus nerve stimulation on NMDAR1 mRNA and GABAAR alpha 1 mRNA in thalamic reticular neucus of pentylenetetrazole-induced epileptic rats]

To study the antiepileptic mechanism of vagus nerve stimulation (VNS), we used the methods of in situ hybridyzation and image analysis to detect the expression of NMDAR1 mRNA and GABAA receptor alpha 1 subunit mRNA (GABAAR alpha 1 mRNA) in the thalamic reticular nuclus. The results show that the NMDAR1 mRNA expression of rats administered pentylenetetrazole(PTZ) is higher than that of control group. By treating with VNS, it decreased. On the contrary, the expression of GABAAR alpha 1 mRNA in the thalamic reticular nuclus of PTZ group rats is lower than that of control group. For rats treated with VNS, it increased. Therefore, it is concluded that VNS may reduce the excitability of cerebral cortices by depressing the activities of glutamic acid receptors (GluR) and by promoting the activities of gamma-aminobutyric acid receptors(GABAR) in thalamic reticular nuclus. So the formation and development of seizures are inhibited.     

Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats

Previous studies have demonstrated that electrical stimulation of the vagus nerve (VNS) delivered at a moderate intensity following a learning experience enhances memory in laboratory rats and human subjects, while VNS at lower or higher intensities has little or no effect. This finding suggests that VNS may affect memory processes by modulating neural plasticity in brain structures associated with memory storage such as the hippocampus. To test this hypothesis, the present study investigated the modulatory effect of VNS on the development of long-term potentiation (LTP) in the dentate gyrus of freely-moving rats. Rats receiving 0.4 mA VNS showed enhanced potentiation of the population spike amplitude for at least 24 h after tetanus relative to the sham-stimulation group. In contrast, no such effect was observed with 0.2 mA VNS. Stimulation at 0.8 mA had a short-term effect and tended to enhance early LTP, but to a lesser extent than did 0.4 mA. The 0.4 mA stimulation was the same intensity that was previously shown to enhance retention performance in an inhibitory avoidance task. These findings suggest that the neural mechanisms underlying the mnemonic effect of VNS may involve modulating synaptic plasticity in the hippocampus. These data also suggest that neural activity in the vagus nerve, occurring as a result of changes in peripheral state, is an important mechanism by which emotional experiences and arousal can enhance the storage of memories of those experiences.     

Antiepileptic effect of electroacupuncture vs. vagus nerve stimulation in the rat thalamus

Our previous study has shown that both electroacupuncture (EA) and vagus nerve stimulation (VNS) can inhibit cortical epileptiform activities induced by pentylenetetrazole (PTZ). The current study compared the effects of EA and VNS on thalamic neuronal responses to PTZ-induced epileptiform activities. Under general anesthesia, extracellular single unit recordings were made from 49 single neurons in the rat ventrobasal (VB) thalamus. The left vagus nerve was stimulated at 30 Hz, 1 or 3 mA for 5 min. For EA, "Dazhui" acupoint (GV14) was stimulated with the same parameters. It was found that (1) the VB thalamic neurons showed epileptiform activities after PTZ injection; (2) VNS and EA could predominantly inhibit the PTZ-induced epileptiform activities in the thalamic neurons. The higher intensity stimulation (3 mA) in either VNS or EA was, however, not associated with a greater inhibition. Our study suggests that both EA and VNS reduce epileptiform activities at the thalamic level, and EA may be an alternative to VNS.     

Vagus nerve stimulation does not affect spatial memory in fast rats, but has both anti-convulsive and pro-convulsive effects on amygdala-kindled seizures

Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy. Using a seizure-prone Fast-kindling rat strain with known comorbid behavioral features, we investigated the effects of VNS on spatial memory, epileptogenesis, kindled seizures and body weight.

Electrodes were implanted in both amygdalae and around the left vagus nerve of 17 rats. Following recovery, rats were tested in the Morris water-maze utilizing a fixed platform paradigm. The VNS group received 2 h of stimulation prior to entering the Morris water-maze. Rats were then tested in the kindling paradigm wherein the VNS group received 2 h of stimulation prior to daily kindling stimulation. Finally, the abortive effects of acute VNS against kindling-induced seizures were determined in fully kindled rats by applying VNS immediately after the kindling pulse. Body weight, water consumption and food intake were measured throughout.

Memory performance in the Morris water-maze was not different between control and vagus nerve stimulation rats. Similarly, kindling rate was unaffected by antecedent VNS. However, pro-convulsive effects (P<0.05) were noted, when VNS was administered prior to the kindling pulse in fully kindled rats. Yet, paradoxically, VNS showed anti-convulsant effects (P<0.01) in those rats when applied immediately after the kindling stimulus. Body weight was significantly lower throughout kindling (P<0.01) in VNS-treated rats compared with controls, which was associated with reduced food intake (P<0.05), but without difference in water consumption.

VNS appears to be devoid of significant cognitive side effects in the Morris water-maze in Fast rats. Although VNS exhibited no prophylactic effect on epileptogenesis or seizure severity when applied prior to the kindling stimulus, it showed significant anti-convulsant effects in fully kindled rats when applied after seizure initiation. Lastly, VNS prevented the weight gain associated with kindling through reduced food intake.     

Participation of the olfactory system in the regulation of food intake

Evoked potentials in the olfactory bulb (OB), lateral hypothalamus (HL) and rostral portion of the nucleus of the tractus solitarius (NTS), were recorded after cervical vagus nerve stimulation. The slow component in the OB only was recorded in the periglomerular layer. Electrolytic lesion of the NTS, abolished the evoked potentials in the OB by vagus nerve stimulation. The results of the present experiments indicate that the pathway from the vagus nerve to OB go into the NTS but probably not into the LH.     

Serotonin receptor subtypes involved in vagus nerve stimulation-induced phrenic long-term facilitation in rats

Episodic vagus nerve stimulation (VNS) induces phrenic long-term facilitation (LTF, a persistent augmentation of phrenic nerve activity after the stimulation ends), sensitive to the serotonin 5-HT(1,2,5,6,7) receptor antagonist methysergide and similar to that elicited by episodic hypoxia or carotid sinus nerve stimulation. This study examined the effect of ketanserin (5-HT(2) antagonist) or clozapine (5-HT(2,6,7) antagonist) on VNS-induced LTF in anesthetized, vagotomized, paralyzed and ventilated rats to determine which receptor subtype(s) is involved. Three episodes of 5 min VNS (50 Hz, 0.1 ms, approximately 500 microA) with 5 min intervals elicited phrenic LTF in control (amplitude: 38% above baseline at 60 min post-VNS) and ketanserin (2 mg x kg(-1), i.p.) pre-treated rats (45%), but not clozapine (3 mg x kg(-1)) rats (8%). These data suggest that unlike hypoxia-induced LTF (5-HT(2) receptor-dependent), VNS-induced LTF requires non-5-HT(2) serotonin receptors, perhaps 5-HT(6) and/or 5-HT(7) subtype(s).     

A new choice for the treatment of epilepsy: electrical auricula-vagus-stimulation

Preliminary reports have suggested that chronic, intermittent electrical stimulation of the cervical vagus nerve (VNS) is an effective treatment for patients who suffered from medically refractory epilepsy. But the traditional VNS is an invasive and implantable procedure that will bring some injury to the patient. Anatomic studies have confirmed the existence of auricular branch of the vagus nerve—Arnold nerve. The Arnold nerve mainly consists of afferent fibers and the superficial sites of the Arnold nerve are optimal for electrical stimulation. We hypothesized that electrical auricula-vagus-stimulation could be a new choice for the treatment of epilepsy.