The influence of electrical stimulation of vagus nerve on elemental composition of dopamine related brain structures in rats

Recent studies of Parkinson's disease indicate that dorsal motor nucleus of nerve vagus is one of the earliest brain areas affected by alpha-synuclein and Lewy bodies pathology. The influence of electrical stimulation of vagus nerve on elemental composition of dopamine related brain structures in rats is investigated. Synchrotron radiation based X-ray fluorescence was applied to the elemental micro-imaging and quantification in thin tissue sections. It was found that elements such as P, S, Cl, K, Ca, Fe, Cu, Zn, Se, Br and Rb are present in motor cortex, corpus striatum, nucleus accumbens, substantia nigra, ventral tectal area, and dorsal motor nucleus of vagus. The topographic analysis shows that macro-elements like P, S, Cl and K are highly concentrated within the fiber bundles of corpus striatum. In contrast the levels of trace elements like Fe and Zn are the lowest in these structures. It was found that statistically significant differences between the animals with electrical stimulation of vagus nerve and the control are observed in the left side of corpus striatum for P (p = 0.04), S (p = 0.02), Cl (p = 0.05), K (p = 0.02), Fe (p = 0.04) and Zn (p = 0.02). The mass fractions of these elements are increased in the group for which the electrical stimulation of vagus nerve was performed. Moreover, the contents of Ca (p = 0.02), Zn (p = 0.07) and Rb (p = 0.04) in substantia nigra of right hemisphere are found to be significantly lower in the group with stimulation of vagus nerve than in the control rats.     

Neuroinhibition in the regulation of emesis

Elucidation of an inhibitory system in the regulation of emesis is presented in this report. Emesis preceded by retching, can be induced in the dog by appropriate electrical stimulation of abdominal vagus nerves at the supradiaphragmatic level. Failure to produce retching or emesis by electrical stimulation of the cervical vagus trunk suggests either that the abdominal vagal emetic afferent does not course in the cervical vagus or that fibers inhibitory to emesis are present. This report presents evidence for afferent fibers inhibitory to retching and emesis in the cervical vagus. Retching and emesis resulting from stimulation of the supradiaphragmatic vagus can be prevented by either transection of the cervical vagus or simultaneous stimulation of the cervical vagus trunk. In addition, retching and emesis occur with stimulation of a fine nerve bundle dissected from the cervical vagus trunk. That the afferent pathway inhibitory to retching and emesis involves pulmonary afferents is suggested by the observation that hyperventilation occurs with stimulation of the cervical vagus trunk.Research supported by U.S.P.H.S. Grant No. FR05339-07     

大鼠蓝斑核对迷走-迷走抑胃反射的加强作用

本文研究了蓝斑核对迷走-迷走抑胃反射的影响。实验结果表明,单独刺激迷走神经中枢端抑制胃电和胃运动,胃电慢波的振幅和胃内压分别下降到对照值的60.9％和45.7％,与对照值相比有明显的统计学意义(P<0.05)。刺激迷走神经中枢端的同时,以弱刺激刺激蓝斑核时,胃电慢渡的振幅和胃内压分别下降到对照值的42.1％和34.1％,与单独刺激迷走神经的效果相比较有非常显著的差异(P<0.01)。本文结果提示:蓝斑核的兴奋加强迷走-迷走抑胃反射。     

多次100Hz TENS治疗慢性炎症痛的适宜参数和可能的神经化学机制研究

本工作在单发佐剂性关节炎慢性痛模型大鼠上比较观察了不同时间间隔和不同强度的多次１００Ｈｚ经皮神经电刺激（ＴＥＮＳ）的治疗效果,并对炎症和ＴＥＮＳ过程中Ｐ物质（ＳＰ）和强啡肽的变化规律及其作用进行了初步探讨。     

电刺激大鼠脊神经皮支对远距离机械感受单位电活动的影响

实验采用分离神经细束的方法,观察逆行电刺激大鼠脊神经背侧皮支后,在相距较远的神经细束上记录到的Aδ和C类机械感受单位电活动的变化。刺激T9脊神经背侧皮支,在T12神经细束上记录到59.3%（16/27）的Aδ和71.2%(37/52）的C类单位在刺激后90～120s放电显著增加。刺激T8脊神经背侧皮支,在T12神经细束上记录到47.8%(11/23）的Aδ单位和36.6%(15/41）的C类单位在刺激后120～150s放电显著增加。大多数单位（18/23）的机械感受阈值在电刺激远距离脊神经背侧皮支后降低。结果表明,逆行电刺激外周感觉神经,可以使相距较远的Aδ和C类机械感受单位致敏,其传入放电增加。     

c-fos Expression in Gracilothalamic Tract Neurons after Electrical Stimulation of the Injured Sciatic Nerve in the Adult Rat

The number of c-fos protein-like immunoreactive (Fos-LI) cells in the gracile nucleus was determined after electrical stimulation at Aα/Aβ-fiber strength of the normal and of the previously injured sciatic nerve in adult rats. No Fos-LI cells were seen after electrical stimulation of the noninjured sciatic nerve, or after sciatic nerve injury without electrical stimulation. However, stimulation 21 days after sciatic nerve transection resulted in numerous Fos-LI cells in the ipsilateral gracile nucleus. Combined Fos immunocytochemistry and retrograde labeling from the thalamus showed that the majority (76%; range = 70–80%) of the cells in the gracile nucleus that expressed Fos-LI after nerve injury projected to the thalamus. The results indicate that morphological, biochemical, and physiological alterations in primary sensory central endings and second-order neurons, which have earlier been demonstrated in the dorsal column nuclei after peripheral nerve injury, are accompanied by changes in the c-fos gene activation pattern after stimulation of the injured sciatic nerve. A substantial number of the c-fos-expressing neurons project to the thalamus.     

Photobiomodulation at a wavelength of 633 nm leads to faster functional recovery than 804 nm after facial nerve injury

We analyzed the effects of photobiomodulation (PBM) of various wavelengths on regeneration of the facial nerve using in vitro and in vivo experimental models. We assessed the antioxidative effect of PBM in geniculate ganglion neurons irradiated with a diode laser at 633 nm, 780 nm and 804 nm. Wavelengths of 633 and 780 nm but not 804 nm inhibited cell death by oxidative stress. We assessed the effects of PBM on functional and morphologic recovery in rats divided into control, facial nerve damage (FND) and FND irradiated with a 633 nm or 804 nm lasers. Injured rats treated with 633-nm light had better facial palsy scores, larger axon diameter and higher expression of Schwann cells compared with the FND group. No positive results were observed in rats irradiated at 804-nm light. These findings indicate that 633-nm PBM promotes accelerated nerve regeneration and improved functional recovery in an injured facial nerve.     

Inhibition of norepinephrine re-uptake by angiotensin in brain

—A method for perfusion of rat brain ventricles accompanied by electrical stimulation of right vagus nerve was used in the study of the re-uptake mechanism of norepinephrine in rat brain. Tritiated norepinephrine was injected into the left lateral brain ventricle. After a 1-hr equilibration period, the brain was perfused, and effluent was collected and assayed for norepinephrine, normetanephrine and acid metabolites by means of column chromatography and liquid scintillation counting. Electrical stimulation of central end of right vagus nerve produced a significant release of norepinephrine and decrease of acid metabolites; this indicates a shift of catecholamines to extracellular sites. Angiotensin (200 ng/min) added to the perfusion fluid potentiated the effect of nerve stimulation. Cocaine, desmethylimipramine and phenoxybenzamine greatly reduced the release of norepinephrine from brain tissue. None on these drugs potentiated the effect of angiotensin. It is concluded that angiotensin prevents re-uptake of norepinephrine released by nerve stimulation. As a naturally occurring, physiologically active peptide, angiotensin seems to be highly specific in modulation of adrenergie neurotransmission, allowing increased extraneuronal accumulation of neurotransmitter.     

电刺激家兔迷走神经中枢端诱导的黑-伯反射中的非联合型学习现象

本文旨在研究电刺激家兔迷走神经诱导的黑-伯（Hering-Breuer,HB）反射中的学习和记忆现象。选择性电刺激家兔迷走神经中枢端（频率10～100Hz,强度20～60μA,波宽0．3ms,持续60s）,观察对膈神经放电的影响。以不同频率电刺激家兔迷走神经可模拟HB反射的两种成分,即类似肺容积增大所致抑制吸气的肺扩张反射和类似肺容积缩小所致加强吸气的肺萎陷反射。（1）长时高频（≥40Hz,60s）电刺激迷走神经可模拟呼吸频率减慢,呼气时程延长的肺扩张反射。随着刺激时间的延长,膈神经放电抑制的程度逐渐衰减,表现为呼吸频率的减慢（主要由呼气时程延长所致）在刺激过程中逐渐减弱或消失,显示为适应性或“习惯化”的现象;刺激结束时呼吸运动呈现反跳性增强,表现为一过性的呼气时程缩短,呼吸频率加快,然后才逐渐恢复正常。长时低频（〈40Hz,60s）电刺激迷走神经可模拟呼吸频率加快、呼气时程缩短的肺萎陷反射。随着刺激时间的延长,膈神经放电增强的程度逐渐衰减,同样表现出“习惯化”现象;刺激结束后,膈神经放电不是突然降低,而是继续衰减,表现为呼气时程逐渐延长,呼吸频率逐渐减慢,直至恢复到前对照水平,表现了刺激后的短时增强效应。（2）HB反射的适应性或“习惯化”程度反向依赖于刺激强度和刺激频率,表现为随着刺激强度和频率的增加,膈神经放电越远离正常基线水平,即爿惯化程度减弱。结果表明,家兔HB反射具有“习惯化”这一非联合型学习现象,反映与其有关的呼吸神经元网络具有突触功能的可翅性,呼吸的中枢调控反射具有一定的适应性。     

Biophysical mechanisms of transient optical stimulation of peripheral nerve

A new method for in vivo neural activation using low-intensity, pulsed infrared light exhibits advantages over standard electrical means by providing contact-free, spatially selective, artifact-free stimulation. Here we investigate the biophysical mechanism underlying this phenomenon by careful examination of possible photobiological effects after absorption-driven light-tissue interaction. The rat sciatic nerve preparation was stimulated in vivo with a Holmium:yttrium aluminum garnet laser (2.12 microm), free electron laser (2.1 microm), alexandrite laser (750 nm), and prototype solid-state laser nerve stimulator (1.87 microm). We systematically determined relative contributions from a list of plausible interaction types resulting in optical stimulation, including thermal, pressure, electric field, and photochemical effects. Collectively, the results support our hypothesis that direct neural activation with pulsed laser light is induced by a thermal transient. We then present data that characterize and quantify the spatial and temporal nature of this required temperature rise, including a measured surface temperature change required for stimulation of the peripheral nerve (6 degrees C-10 degrees C). This interaction is a photothermal effect from moderate, transient tissue heating, a temporally and spatially mediated temperature gradient at the axon level (3.8 degrees C-6.4 degrees C), resulting in direct or indirect activation of transmembrane ion channels causing action potential generation.     

Canine vagus nerve stores cholecystokinin-58 and -8 but releases only cholecystokinin-8 upon electrical vagal stimulation

Cholecystokinin-58 has been shown to be the major form of cholecystokinin (CCK) released to the circulation upon lumenal stimulation of the small intestine in humans and dogs. In anesthetized dogs, electrical vagal stimulation evokes pancreatic exocrine secretion that is in part mediated through the release of CCK. We studied the molecular form of CCK stored in canine vagus nerves and that released into circulation upon electrical vagal stimulation. Gel filtration and radioimmunoassay of the water and acid extracts of canine vagus nerves indicated CCK-8 (35%) and CCK-58 (65%) as the major molecular forms in the vagus nerve. Both forms of CCK isolated from the vagal extracts were equally bioactive as the standard CCK-8 and CCK-58, respectively, in stimulation of amylase release from isolated rat pancreatic acini. Analysis of plasma collected after electrical vagal stimulation indicated that CCK-8 is the only form released into the circulation. The release of CCK-8 upon electrical vagal stimulation was not affected by application of lidocaine to the upper small intestinal mucosa, suggesting that it was released from vagal nerve terminals.     

Further studies on absorption changes arising in dye-stained nerves during excitation

Summary Changes in light absorption during nerve excitation (absorption responses) were detected from the crab leg nerve, the rabbit vagus, and the rat superior cervical ganglion (SCG) stained with a merocyanine-rhodanine. Dependences of the responses on the wavelength and polarization of the incident light (absorption spectra) showed characteristic features with the respective nerves. In the crab nerve, the pattern of response spectra was precisely analyzed based on the previously proposed scheme, which included the shift of absorption bands and the statistical reorientation of absorption oscillators of the dye molecules in the membrane matrix during nerve excitation. Different patterns of the response spectra between the crab nerve and the rabbit vagus suggested that distinct physicochemical environments of the dye occurred in these two classes of membranes. On the other hand, the characteristic pattern that arose in the rat SCG was explained by its morphological form, that is, unlike those in a bundle of axons, the membrane elements in the ganglion were randomly oriented with respect to the direction of the light polarization.     

Parasympathetic cholinergic vasodilator mechanism in the terminal liver microcirculation in rats.

Changes in the diameter of liver sinusoids were studied by an intravital television microscope method in pentobarbital-anaesthetized rats. Dilatation of liver sinusoids was observed during parasympathetic neural stimulation and during acetylcholine administration. Frequency-dependent stimulation-effect relationships were obtained by electrical excitation of intact vagus nerves at supramaximal intensity from 2 to 8 Hz. Acetylcholine concentration-effect relationships were also obtained by intraportal venous infusions of acetylcholine 30 microliter for 5 s from 10(-9) to 10(-2) mol.1(-1). Systemic cholinergic receptor blockade with atropine (1 mg.kg-1) markedly reduced dilatation of liver sinusoids produced by both vagus nerve stimulation and acetylcholine administration. Changes in diameter of liver sinusoids with frequency of neural stimulation and with concentration of administered acetylcholine were also expressed as percentage of observed maximum effect and the respective stimulation-effect curves were constructed such that at a certain percentage of diameter change, the equivalent level of vagus nerve activity was represented by a given concentration of administered acetylcholine. Liver plasma concentration of acetylcholine presumably released during electrical vagal stimulation and reaching liver sinusoids was also estimated and found to be within physiological range. It is therefore proposed that rat liver sinusoids have the capacity for parasympathetic cholinergic vasodilatation.     

Lack of CCK-like pancreatic stimulation by intraduodenal amino acids in the anesthetized cat

We have attempted to demonstrate a pancreatic secretory response to intraduodenal amino acids in the anesthetized cat. In four cats stimulated with supramaximal doses of secretin, protein concentrations in pancreatic juice were measured after intraduodenal bolus injection of various amino acids, IV CCK, or electrical stimulation of the vagus nerve. In addition, the duodenum was perfused with phenylalanine (50 mM) for 30 min in two cats, and the vagus nerve stimulated electrically for 15 min in one. In no case did amino acids produce pancreatic protein secretion, whereas CCK and vagal stimulation always did so. We conclude that this insensitivity to amino acids in the cat is a species difference from the dog and man.     

Evaluation of combined effects of brief electrical stimulation and Schwann-like cells on sciatic nerve injury model

Severe nerve injuries can be treated with electrical stimulation and stem cell therapies, but little is known about the potential benefits of combining these two treatments. In an effort to investigate this combination, we conducted a study to evaluate the effectiveness of electrical stimulation and Schwann-like cell transplantation in female Wistar albino rats. Our study consisted of five groups of rats: a sham group, an injury group, an electrical stimulation group, a Schwann-like cell group, and a combination group. The experimental groups received electrical stimulation, Schwann-like cell transplantation, or both. The animals sciatic function index was evaluated during a 6-week recovery period, and nerve conduction velocity, wet muscle mass, and nerve tissues were also analyzed. The results of the study showed that all experimental groups had a faster functional recovery compared to the injury group, although the difference between groups was not statistically significant. Both the combination group and the Schwann-like cell transplantation group had a higher nerve conduction velocity compared to the other experimental groups. However, there was no significant difference between the combination and Schwann-like cell transplantation groups. Nonetheless, histological analysis showed a better axonal reorganization in the combination group. The study provides preliminary evidence of the potential benefits of combining electrical stimulation and Schwann-like cell transplantation in treating severe nerve injuries. However, further studies with larger sample sizes are needed to confirm these findings and optimize the treatment parameters.     

The effects of transcranial laser photobiomodulation and neuromuscular electrical stimulation in the treatment of post-stroke dysfunctions

Post-stroke sequelae includes loss functions, such as cognitive and sensory-motor which lead to emotional and social problems, reducing quality of life and well-being. The main aim of our study was to investigate the effects of transcranial laser photobiomodulation together with neuromuscular electrical stimulation (NMES) in post-stroke patients. We performed a clinical trial and an ex vivo study. For the clinical trial, hemiplegic patients were separated into two groups: Treated Group (TG): Hemiplegics treated with transcranial laser (on) associated with NMES (on) and; Placebo Group (PG): Hemiplegics treated with placebo transcranial laser (off) associated with NMES (on). The cluster prototype includes 12 diode laser beams (4 × 660 nm, 4 × 808 nm and 4 × 980 nm) with average power of 720 mW per cluster applied during one minute, leading to 43.2 J energy per cluster. Fifteen regions for all head were irradiated by cluster, leading to 648 J energy per session. The parameters of NMES of the paretic limbs to generate extension wrist and ankle dorsiflexion were symmetrical biphasic rectangular waveforms, 50 Hz frequency, 250 μs pulse duration, and adjustable intensity to maintain the maximum range of motion (amplitude between 0 and 150 mA). Our clinical trial showed improvement of cognitive function, pain relief, greater manual dexterity, enhancement of physical and social–emotional health which lead to better quality of life and well-being. There was also increased temperature in the treated regions with laser and NMES. For the ex vivo study, the distribution of infrared and red radiation after penetration through the cranium and hemihead of cadavers were showed. Therefore, transcranial laser photobiomodulation associated with NMES can be an important therapeutic resource for rehabilitation after stroke.     

Tripelennamine: enhancement of brain-stimulation reward

Thresholds for reinforcing electrical stimulation to the medial forebrain bundle were determined in rats by means of a rate-free psychophysical method. The acute administration of tripelennamine lowered the threshold for rewarding brain stimulation in a dose-dependent manner. These results suggest that the abuse liability of tripelennamine may be related to its ability to sensitize the central neural pathway that mediates reward.     

消化管括约肌部VIP免疫活性神经细胞分布

应用免疫组织化学方法研究了食管下部,幽门和回盲部肌间神经丛内ＶＩＰ免疫活性神经细胞的分布。ＶＩＰ免疫活性神经细胞在括约肌部比相邻部位数量多。并用Ｏｐｅｎ－ｔｉＰ法测量了刺激迷走神经后食管下段括约肌部压力的变化。用高阈值参数电刺激迷走神经引起预先投给阿托品的狗食管下段括约肌部压力的降低;这样条件下延长迷走神经刺激引起肌间神经丛内ＶＩＰ免疫活性神经细胞数量明显增加。由此结果提示含有或产生ＶＩＰ的神经细胞可能接受迷走神经的控制。由于刺激节前迷走神经纤维可能作用到这些细胞。