Phosphoinositide metabolism in rat superior cervical ganglion, vagus and phrenic nerve: effects of electrical stimulation and various blocking agents

Abstract— Paired vagus nerves, phrenic nerves or superior cervical ganglia from rats were incubated at 37 C for various times in a simple salt solution containing glucose and ³²P_i. One of the pair was usually stimulated electrically for 30 or 60 min. Stimulation of vagus nerve for 30 min increased phosphate incorporation into all the phospholipids studied but the increase was significant only in the case of triphos-phoinositide and diphosphoinositide. This increase was not accompanied by increased labelling of the nucleotide labile phosphate pool. Tetrodotoxin at concentrations sufficient to block transmission had no effect upon phospholipid labelling in vagus or phrenic nerve. Ouabain at blocking concentration did not affect polyphosphoinositide metabolism in vagus nerve but increased [³²P]labelling of the other phospholipids. Hemicholinium-3 increased the labelling of all three phosphoinositides in the sympathetic ganglia but the increase in phosphatidylinositol labelling due to electrical stimulation was not seen in the presence of this inhibitor.     

Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study

IntroductionVagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve. In the present study, we determined whether tVNS is a feasible and safe procedure and investigated its putative anti-inflammatory effects during experimental human endotoxemia.MethodsWe performed a randomized double-blind sham-controlled study in healthy male volunteers. A stimulation catheter was inserted in the left internal jugular vein at spinal level C5–C7, adjacent to the vagus nerve. In the tVNS group (n = 10), stimulation was continuously performed for 30 minutes (0–10 V, 1 ms, 20 Hz), starting 10 minutes before intravenous administration of 2 ng kg⁻¹Escherichia coli lipopolysaccharide (LPS). Sham-instrumented subjects (n = 10) received no electrical stimulation.ResultsNo serious adverse events occurred throughout the study. In the tVNS group, stimulation of the vagus nerve was achieved as indicated by laryngeal vibration. Endotoxemia resulted in fever, flu-like symptoms, and hemodynamic changes that were unaffected by tVNS. Furthermore, plasma levels of inflammatory cytokines increased sharply during endotoxemia, but responses were similar between groups. Finally, cytokine production by leukocytes stimulated with LPS ex vivo, as well as neutrophil phagocytosis capacity, were not influenced by tVNS.ConclusionstVNS is feasible and safe, but does not modulate the innate immune response in humans in vivo during experimental human endotoxemia.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01944228","term_id":"NCT01944228"}}NCT01944228. Registered 12 September 2013.     

Intraoperative monitoring of the abducens nerve in extended endonasal endoscopic approach: A pilot study technical report

BackgroundTo determine the reliability and usefulness of intraoperative monitoring of the abducens nerve during extended endonasal endoscopic skull base tumor resection.MethodsWe performed abducens nerve intraoperative monitoring in 8 patients with giant clival lesions recording with needle electrodes sutured directly into the lateral rectus muscles of the eye to evaluate spontaneous electromyographic activity and triggered responses following stimulation of the abducens nerves.ResultsA total of 16 abducens nerves were successfully recorded during endoscopic endonasal skull base surgeries. Neurotonic discharges were seen in two patients (12% [2/16] abducens nerves). Compound muscle action potentials of the abducens nerves were evoked with 0.1–4 mA and maintained without changes during the neurosurgical procedures. No patient had new neurological deficits or ophthalmological complications post-surgery.ConclusionsIntraoperative monitoring of the abducens nerve during the extended endonasal endoscopic approach to skull base tumors appears to be a safe method with the potential to prevent neural injury through the evaluation of neurotonic discharges and triggered responses.     

A comparative study of oculomotor,trochlear and abducens nerves in Arabian foals

We investigated the microscopic structure of transverse sections of the oculomotor, trochlear and abducens nerves of Arabian foals using stereological methods. Bilateral nerve pairs from 2-month-old female Arabian foals were analyzed. The tissues were embedded in plastic blocks, then 1 µm thick sections were cut and stained with osmium tetroxide and methylene blue-azure II. Stereology was performed using light microscopy. Morphometry showed that the right and left pairs of nerves were similar. The transverse sectional areas of the oculomotor, trochlear and abducens nerves were 1.93 ± 0.19 mm², 0.32 ± 0.06 mm² and 0.70 ± 0.08 mm², respectively. The oculomotor nerve exhibited a significantly greater number of myelinated axons (16755 ± 1279) and trochlear (2656 ± 494) and the abducens nerves (4468 ± 447). The ratio of the axon diameter to myelinated nerve fiber diameter was 0.58, 0.55 and 0.55 for the oculomotor, trochlear and abducens nerves, respectively. Of the three nerves studied, the abducens nerve exhibited the greatest nerve fiber area, myelin area, nerve and axon diameters, and myelin thickness. The ratio of small myelinated nerve fibers was greatest in the oculomotor nerve.     

New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy

To evaluate ultrasonographic (US) cross-sectional areas (CSAs) of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs) and between tunnel (T) and pre-tunnel (PT) ulnar CSAs (∆TPTs) in leprosy patients (LPs) and healthy volunteers (HVs). Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M) and common fibular (CF) nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p < 0.0001) at the PT (5.67/9.78 mm²⁾ and T (6.50/10.94 mm²⁾ points, as well as at the M (5.85/8.48 mm²⁾ and CF (8.17/14.14 mm²⁾ nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm² and 68-85% for the PT point, 7.35 mm² and 71-78% for the T point, 6.75 mm² and 62-75% for the M nerve and 9.55 mm² and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 80%) and ∆TPT had the highest specificity (> 90%). New sonographic peripheral nerve measurements (∆CSAs and ∆TPT) provide an important methodological improvement in the detection of leprosy neuropathy.     

千频交流电刺激在外周神经传导阻断中的作用

感觉、运动或自主神经系统的异常病理活动与疼痛和痉挛等多种神经机能障碍有关。千频交流电（kilohertz frequency alternating current，KHFAC）刺激是一种阻断异常病理活动在外周神经内传导的有效方法，它在缓解相关神经机能障碍方面具有临床应用潜力。KHFAC产生的神经传导阻断受千频信号波形和参数、阻断电极设置和位置以及神经纤维类型和直径等因素影响，具有快速性、可控性、可逆性、局部作用和副作用小的特点。但是，在产生完全传导阻断前，KHFAC首先在靶向神经上激活一簇高频初始放电，这种初始响应可能导致肌肉抽搐或疼痛感。同时，在撤去KHFAC后处于阻断状态的靶向神经需要经历一段时间才能恢复正常传导能力，这是该技术导致的后续效应。目前，关于KHFAC阻断神经传导的生物物理机制假说包括千频信号诱发K⁺通道激活和Na⁺通道失活。本文首先介绍了KHFAC技术的电生理实验研究方法和计算模型仿真方法，然后综述目前关于KHFAC作用下神经传导阻断的研究进展，重点论述初始响应特性及消除方法、传导阻断的后续效应、刺激波形和参数的影响、电极设置与位置的影响以及该技术潜在的临床应用，同时归纳KHFAC阻断神经传导的生物物理机制，最后对该技术未来的相关研究进行展望。     

New techniques in female pudendal somatosensory evoked potential testing

Objective—The primary nerves innervating the female genitalia are the dorsal nerve of the clitoris (DNC) and the perineal nerve, which innervate the clitoris and the external genitalia/distal vagina, respectively. We describe two novel electrodiagnostic techniques for evaluating the integrity of these female genital somatosensory pathways.

Subjects and methods—Seventy-seven healthy women (mean age 29.3 years) were enrolled for this study. We performed DNC somatosensory evoked potentials (SEPs), stimulating through self-adhesive disk electrodes on either side of the clitoris. Perineal nerve SEPs were evoked through a vaginal probe. Cortical responses were measured through cup electrodes affixed to the scalp at Cpz and Fpz. Stimulus parameters were duration 0.1?ms, frequency 4.1?Hz, filters 5–5,000?Hz, at three times sensory threshold.

Results—DNC and perineal nerve SEPs from both the right and left sides were reproducible and easily discerned. The mean P1 latencies were: right DNC 39.4?ms (SD 2.8?ms), left DNC 39.3?ms (SD 3.3?ms), right perineal nerve 37.8?ms (SD 3.4?ms), left perineal nerve 37.6?ms (SD 3.1?ms). We recorded SEP responses from 90 to 92% of subjects for the DNC, and 69% for the perineal nerve.

Conclusions—We are able to evoke somatosensory potentials from the four primary somatic nerves that mediate female genital cutaneous sensation. In healthy subjects, the DNC responses are robust and maintain laterality. The perineal nerve responses are less consistently obtained, but when recorded, are easily discerned. These preliminary data provide a foundation from which to study female genital innervation, particularly as it applies to sexual function.     

Effects of pneumogastric nerve stimulation and injection of a beta 2 stimulant (terbutaline) on the lipid composition of the alveolar lining fluid and on pulmonary compliance in the rat

The effects of vagal stimulation and of terbutaline injection on lipidic composition of alveolar fluid and pulmonary compliance were studied. Three groups of rats were used: control, after right vagus nerve stimulation, after 0.2 mg terbutaline injection. The lungs of the rats were isolated. We studied pulmonary pressure-volume curves with air and we measured pulmonary compliance. We realised an alveolar lavage to obtain alveolar lipids. We observed: Vagus nerve stimulation and beta 2 agonist significantly increased fatty acids of total lipids respectively by 52.5% and 25.5% and phospholipids, respectively by 43.6% and 25.7%. beta 2 agonist did not change fatty acid composition of total lipids and phospholipids. Right vagus nerve stimulation increased the percentage of palmitic acid in phospholipids and decreased the percentage of saturated fatty acids and of palmitic acid in total lipids. Terbutaline injection induced more significant changes in pressure-volume curves and in pulmonary compliance than right vagus nerve stimulation. Our results suggest that both vagal stimulation and beta 2 agonists increase lipid release in alveolar lining, but only vagal stimulation modifies the composition of these lipids. These modifications could be, at least in part, correlated with the changes observed in the pressure-volume curves.     

Primitive nervous systems: Electrical activity in ventral nerve cords of the flatworm,Notoplana acticola

Electrical activity evoked in the major cords of the ventral submuscular nerve plexus were measured. Recordings and stimulation utilized suction electrodes attached directly to exposed nerve cords. Four categories have been recorded: (a) short latency spikes which have relatively high thresholds and appear to be single units; (b) short duration fast compound spikes that are made up of a large units; (c) long duration compound potentials that are made up from a large number of smaller units, and (d) small amplitude potentials with long latencies and a characteristic shape. These can be conducted diffesely through the nerve plexus. The first two categories of spikes are called “fast” potentials because of their characteristic rise and fall times and the last categories are known as “diffuse” potentials. The spikelike fast potentials were only recorded from the main trunks (nerves VI), while diffuse potentials could also be recorded from side branches of these nerves. The diffuse potential appears to be concluded throughout the plexus but preferential conducting pathways occur lesions. Both diffuse and fast potentials show facilitation of response to repeated stimulation. Facilitation can be demonstrated in the presence of high Mg²⁺ concentrations. Conductance of the diffuse potential also occurs in the presence of high ambient Mg²⁺. In Ca²⁺ free medium containing 1-mM EGTA one can also observe facilitatory events. The possibility of Mg²⁺-insensitive synapses is discussed.     

Bilateral Nerve Alterations in a Unilateral Experimental Neurotrophic Keratopathy Model: A Lateral Conjunctival Approach for Trigeminal Axotomy

To study bilateral nerve changes in a newly developed novel mouse model for neurotrophic keratopathy by approaching the trigeminal nerve from the lateral fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was performed in adult BALB/c mice at the posterior sclera. Axotomized, contralateral, and sham-treated corneas were excised on post-operative days 1, 3, 5, 7 and 14 and immunofluorescence histochemistry was performed with anti-β-tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated using a nylon thread. The survival rate was 100% with minimal bleeding during axotomy and a surgical time of 8±0.5 minutes. The blink reflex was diminished at day 1 after axotomy, but remained intact in the contralateral eyes in all mice. The central and peripheral subbasal nerves were not detectable in the axotomized cornea at day 1 (p<0.001), compared to normal eyes (101.3±14.8 and 69.7±12.0 mm/mm² centrally and peripherally). Interestingly, the subbasal nerve density in the contralateral non-surgical eyes also decreased significantly to 62.4±2.8 mm/mm² in the center from day 1 (p<0.001), but did not change in the periphery (77.3±11.7 mm/mm², P = 0.819). Our novel trigeminal axotomy mouse model is highly effective, less invasive, rapid, and has a high survival rate, demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased subbasal nerves in contralateral eyes after unilateral axotomy. This model will allow investigating the effects of corneal nerve damage and serves as a new model for neurotrophic keratopathy.     

Die Halsäste des Nervus vagus beim Alpaka,Lama guanicoe pacos (Linné 1758)

Demmel, U. 1980. Die Halsäste des Nervus vagus beim Alpaka, Lama guanicoe pacos (Linné 1758). [The branches of the vagus nerve in the neck of Alpaka, Lama guanicoe pacos (Linné 1758).] (Anatomisches Institut der Universität Köln, Bundesrepublik Deutschland.) — Acta zool. (Stockh.) 61(3): 141–146. Dissections of two newborn and two adult alpacas have shown: that the trapezius musculature of either side is supplied by branches of seven cervical spinal nerves and not by the external ramus of truncus nervi accessorii as in mammals in general; that the nerves which innervate the inner laryngic muscles as well as the mucous membrane of the lower part of the larynx are given off from the main trunk of the vagus nerve just outside the jugular foramen; that a nerve corresponding to the n. laryngeus recurrens of other mammals is absent. It is concluded that the lack of recurvation of the inferior laryngic nerve and the absence of the spinal part of the accessory nerve are character states of tylopod artiodactyls.     

Prevalence of accessory deep peroneal nerve in referred patients to an electrodiagnostic medicine clinic

Background

Variations in the branching of posterior cord are important during surgical approaches to the axilla and upper arm, administration of anesthetic blocks, interpreting effects of nervous compressions and in repair of plexus injuries. The patterns of branching show population differences. Data from the African population is scarce.

Objective

To describe the branching pattern of the posterior cord in a Kenyan population.

Materials and methods

Seventy-five brachial plexuses from 68 formalin fixed cadavers were explored by gross dissection. Origin and order of branching of the posterior cord was recorded. Representative photographs were then taken using a digital camera (Sony Cybershot ^R, W200, 7.2 Megapixels).

Results

Only 8 out of 75 (10.7%) posterior cords showed the classical branching pattern. Forty three (57.3%) lower subscapular, 8(10.3%) thoracodorsal and 8(10.3%) upper subscapular nerves came from the axillary nerve instead of directly from posterior cord. A new finding was that in 4(5.3%) and in 3(4%) the medial cutaneous nerves of the arm and forearm respectively originated from the posterior cord in contrast to their usual origin from the medial cord.

Conclusions

Majority of posterior cords in studied population display a wide range of variations. Anesthesiologists administering local anesthetic blocks, clinicians interpreting effects of nerve injuries of the upper limb and surgeons operating in the axilla should be aware of these patterns to avoid inadvertent injury. A wider study of the branching pattern of infraclavicular brachial plexus is recommended.     

PHOSPHOINOSITIDES AND OTHER PHOSPHOLIPIDS IN SYMPATHETIC GANGLIA AND NERVE TRUNKS OF RATS

Abstract— Paired vagus nerves, phrenic nerves or superior cervical sympathetic ganglia from adult white rats were incubated for 4 h at 37°C in a bicarbonate-buffered physiological solution containing glucose and ³²P₁. At the end of incubation triphosphoinositide (TPI) contained more ³²P than any other lipid in the vagus nerves and was second only to phosphatidylcholine (PC) in the phrenic nerves. In the sympathetic ganglia phosphatidylinositol (PI) contained more ³²P than did TPI, but both had less than PC. Conducted nerve impulses, initiated by electrical stimulation during the final 3 h of incubation, caused a highly significant increase in the [32P]-labelling of PI in ganglia (as previously reported) probably decreased the labelling of TPI in the vagus nerves, and decreased the labelling of phosphatidylethanolamine (PE) in the ganglia. Addition to the incubation medium of §- or γ-hexachlorocyclohexane (analogs of inositol) reversibly blocked transmission through the sympathetic ganglia at concentrations less than 0·1 mM. The §-isomer also blocked conduction along axons at similar concentrations; only the γ-isomer (lindane) exerted a selective effect on synaptic transmission. In the ganglia, the §-isomer increased the [³²P]-labelling of PI and diphosphoinositide (DPI) relative to that of PC. The γ-isomer did not affect the relative labelling of PI in the ganglia, whereas it decreased that of TPI, but only at relatively high concentrations. Thus, various affects of the hexachlorocyclohexanes were not explicable by assuming that they acted as analog inhibitors of inositol metabolism. In the ganglia, the hexachlorocyclohexanes reduced the effect of neuronal activity on the labelling of PI in proportion to the extent by which they blocked transmission. This metabolic effect was therefore presumed to be secondary to a ganglionic blocking action.     

A novel animal model of partial optic nerve transection established using an optic nerve quantitative amputator

Background

Research into retinal ganglion cell (RGC) degeneration and neuroprotection after optic nerve injury has received considerable attention and the establishment of simple and effective animal models is of critical importance for future progress.

Methodology/Principal Findings

In the present study, the optic nerves of Wistar rats were semi-transected selectively with a novel optic nerve quantitative amputator. The variation in RGC density was observed with retro-labeled fluorogold at different time points after nerve injury. The densities of surviving RGCs in the experimental eyes at different time points were 1113.69±188.83 RGC/mm² (the survival rate was 63.81% compared with the contralateral eye of the same animal) 1 week post surgery; 748.22±134.75 /mm² (46.16% survival rate) 2 weeks post surgery; 505.03±118.67 /mm² (30.52% survival rate) 4 weeks post surgery; 436.86±76.36 /mm² (24.01% survival rate) 8 weeks post surgery; and 378.20±66.74 /mm² (20.30% survival rate) 12 weeks post surgery. Simultaneously, we also measured the axonal distribution of optic nerve fibers; the latency and amplitude of pattern visual evoke potentials (P-VEP); and the variation in pupil diameter response to pupillary light reflex. All of these observations and profiles were consistent with post injury variation characteristics of the optic nerve. These results indicate that we effectively simulated the pathological process of primary and secondary injury after optic nerve injury.

Conclusions/Significance

The present quantitative transection optic nerve injury model has increased reproducibility, effectiveness and uniformity. This model is an ideal animal model to provide a foundation for researching new treatments for nerve repair after optic nerve and/or central nerve injury.     

Airway neutral endopeptidase-like enzyme modulates tachykinin-induced bronchoconstriction in vivo

To determine whether neutral endopeptidase (NEP), also called enkephalinase (EC 3.4.24.11), modulates the effects of exogenous and endogenous tachykinins in vivo, we studied the effects of aerosolized phosphoramidon, a specific NEP inhibitor, on the responses to aerosolized substance P (SP) and on the atropine-resistant response to vagus nerve stimulation (10 V, 5 ms for 20 s) in guinea pigs. SP alone (10(-7) to 10(-4) M; each concentration, 7 breaths) caused no change in total pulmonary resistance (RL, P greater than 0.5). Phosphoramidon (10(-4) M, 90 breaths) caused no change either in base-line RL (P greater than 0.5) or in the response to aerosolized acetylcholine (P greater than 0.5). However, in the presence of phosphoramidon, SP (7 breaths) produced a concentration-dependent increase in RL at concentrations greater than or equal to 10(-5) M (P less than 0.001). Phosphoramidon (10(-7) to 10(-4) M; each concentration, 90 breaths) induced a concentration-dependent potentiation of SP-induced bronchoconstriction (10(-4) M, 7 breaths; P less than 0.01). Vagus nerve stimulation (0.5-3 Hz), in the presence of atropine, induced a frequency-dependent increase in RL (P less than 0.001). Phosphoramidon potentiated the atropine-resistant responses to vagus nerve stimulation (P less than 0.001) at frequencies greater than 0.5 Hz. The tachykinin antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P abolished the effects of phosphoramidon on the atropine-resistant response to vagus nerve stimulation (2 Hz, P less than 0.005). NEP-like activity in tracheal homogenates of guinea pig was inhibited by phosphoramidon with a concentration producing 50% inhibition of 5.3 +/- 0.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.     

Cortical potentials evoked by epidural stimulation of the cervical and thoracic spinal cord in man

Scalp somatosensory evoked potentials (SEPs) were recorded after electrical stimulation of the spinal cord in humans. Stimulating electrodes were placed at different vertebral levels of the epidural space over the midline of the posterior aspect of the spinal cord. The wave form of the response differed according to the level of the stimulating epidural electrodes. Cervical stimulation elicited an SEP very similar to that produced by stimulation of upper extremity nerves, e.g., bilateral median nerve SEP, but with a shorter latency. Epidural stimulation of the lower thoracic cord elicited an SEP similar to that produced by stimulation of lower extremity nerves. The results of upper thoracic stimulation appeared as a mixed upper and lower extremity type of SEP. The overall amplitudes of SEPs elicited by the epidural stimulation were higher than SEPs elicited by peripheral nerve stimulation. In 4 patients the CV along the spinal cord was calculated from the difference in latencies of the cortical responses to stimulation at two different vertebral levels. The CVs were in the range of 45–65 m/sec. The method was shown to be promising for future study of spinal cord dysfunctions.     

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.     

Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo

Fibroblast growth factor (FGF) signalling has important roles in the development of the embryonic pharyngeal (branchial) arches, but its effects on innervation of the arches and associated structures have not been studied extensively. We investigated the consequences of deleting two receptor tyrosine kinase (RTK) antagonists of the Sprouty (Spry) gene family on the early development of the branchial nerves. The morphology of the facial, glossopharyngeal and vagus nerves are abnormal in Spry1−/−;Spry2−/− embryos. We identify specific defects in the epibranchial placodes and neural crest, which contribute sensory neurons and glia to these nerves. A dissection of the tissue-specific roles of these genes in branchial nerve development shows that Sprouty gene deletion in the pharyngeal epithelia can affect both placode formation and neural crest fate. However, epithelial-specific gene deletion only results in defects in the facial nerve and not the glossopharyngeal and vagus nerves, suggesting that the facial nerve is most sensitive to perturbations in RTK signalling. Reducing the Fgf8 gene dosage only partially rescued defects in the glossopharyngeal nerve and was not sufficient to rescue facial nerve defects, suggesting that FGF8 is functionally redundant with other RTK ligands during facial nerve development.     

Involvement of intracellular calcium in the phosphate efflux from mammalian nonmyelinated nerve fibers

Summary Phosphate efflux was measured as the fractional rate of loss of radioactivity from desheathed rabbit vagus nerves after loading with radiophosphate. The effects of strategies designed to increase intracellular calcium were investigated. At the same time, the exchangeable calcium content was measured using⁴⁵Ca. Application of calcium ionophore A23187 increased phosphate efflux in the presence of external calcium in parallel with an increase in calcium content. In the absence of external calcium, there was only a late, small increase in phosphate efflux. For nerves already treated with the calcium ionophore, the phosphate efflux was sensitive to small changes in external calcium, in the range 0.2 to 2mm calcium, whereas similar increases in calcium in absence of ionophore gave much smaller increases in phosphate efflux. Removal of external sodium (choline substitution) produced an initial increase in phosphate efflux followed by a fall. The initial increase in phosphate efflux was much larger in the presence of calcium, than in its absence. The difference was again paralleled by an increase in calcium content of the preparation, thought to be due to inhibition of Na/Ca exchange by removal of external sodium. Measurements of ATP content and ATP, ADP, phosphate and creatine phosphate ratios did not indicate significant metabolic changes when the calcium content was increased. Stimulation of phosphate efflux by an increase in intracellular calcium may be due to stimulation of phospholipid metabolism. Alternatively, it is suggested that stimulation of phosphate efflux is associated with the stimulation of calcium efflux, possibly by cotransport of calcium and phosphate.