Hyperuricemia in the rat following hypothalamic stimulation

Ventromedial hypothalamic electrical stimulation elicited a marked elevation of plasma uric acid with a rise in plasma allantoin in the rat. The magnitude of this hyperuricemia was greater than that of the hyperglycemia which was also produced by the ventromedial stimulation. On the other hand, lateral hypothalamic stimulation did not significantly affect the plasma levels of either of the purine metabolites. These results strongly indicate that the ventromedial hypothalamus is specifically very active in producing hyperuricemia in the rat.     

刺激兔下丘脑室旁核诱发的心律失常与增压反应

在60只局麻与肌松剂制动的家兔,观察到用0.1—0.4mA,50Hz,1ms 的方波电刺激下丘脑室旁核(PV)能诱发频发性心律失常(包括室性与室上性期前收缩)及显著的动脉血压升高。与同侧的下丘脑外侧区(LHA)及腹内侧核(VMH)相比,刺激PV诱发期前收缩的次数更为频繁,增压反应幅度较大,且所需阈值亦较低。较低强度刺激LHA 在部分兔能引起血压下降与心率减慢,而PV 则一致地诱发增压反应。电刺激腓深神经能抑制刺激PV诱发的期前收缩,但在中脑中央灰质微量注射吗啡或电解毁损只能完全阻断刺激VMH诱发的期前收缩,而不能完全阻断PV诱发的期前收缩。这些结果提示,PV是下丘脑中诱发心律失常与血压增高的高反应区之一,并且可能具有不同于LHA或VMH的神经机制或下行神经通路。     

电刺激兔下丘脑不同部位诱发的房性心律失常

在57只麻醉家兔,用同心圆双极电极刺激右侧下丘脑外侧区、前区、后区、背内侧核、腹内侧核五个不同部位,观察到均能诱发房性早搏等房性心律失常,且存在相对特异性。在用1mA 强度电刺激时,以前三个部位的诱发率较高。如预先轻度灼伤右心房后再刺激下丘脑外侧区或前区,可显著提高房性心律失常的发生率,并使诱发房颤等严重房性心律失常的机会有所增加。在同时描记股动脉血压的家兔中,观察到房性心律失常均在血压增高时出现,并以下丘脑后区、前区、外侧区的增压反应较为显著。在下丘脑外侧区增加刺激强度时,房性心律失常的发生率不随增压平均值的增加而递增,与室性心律失常不同。切断双侧颈迷走神经干后再刺激下丘脑同一部位时,原能诱发房性早搏的家兔全部不再诱发,而原能诱发以室性早搏为主的室性心律失常的部分兔仍能发生。这些结果提示,电刺激下丘脑诱发房性心律失常的机制与室性心律失常有所不同。     

大肠杆菌的直流电场刺激过程

以钛网电极和铂网电极对培养瓶中大肠杆菌生长过程进行加电刺激,研究其在直流电场作用下的生长情况,并结合循环伏安扫描、恒电流、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)及测定菌体ATP酶活力等技术对大肠杆菌的直流电场刺激过程进行研究。结果表明,在0-0.2275mA/cm2范围内,随着电流密度的增加,直流电场对大肠杆菌生长量的增长促进作用逐渐增加,而0.0455mA/cm2的电场则是获得最大活菌量的最适电流密度;通过对析氢活性不同的铂网电极与钛网电极通加相同电流密度的电场,发现铂电极培养体系菌体生长优于钛电极培养体系菌体的生长。经验证发现引起这种变化的原因主要是水的阴极电解产物吸附氢和氢气比例的不同引起的;同时发现在0.091mA/cm2电流密度下,直流电场能有效提高ATP酶的活力,在8h时通电菌样酶活为不通电菌样酶活的3.2倍;通过对0.0455mA/cm2直流电场刺激后的菌体蛋白进行SDS-PAGE分析发现加电菌体在分子量25kD与35kD左右多肽表达量明显高于不加电菌体的多肽表达量,而在分子量为66.2kD左右时多肽表达量低于不加电菌体多肽表达量。     

Visual illusions induced by electrical stimulation of the labyrinth

In normal subjects, electrical stimulation of the labyrinth with surface electrodes located on the mastoid process induced illusions of shifting of a fixed point of light in darkness similar to the oculogyral illusion induced by rotatory vestibular stimulation. Monoaural anodal stimulation of the right labyrinth induced apparent shift of the target to the left; with cathodal stimulation, it shifted to the right; threshold current was 0.35–0.6 mA. When the current strength increased, the amplitude and rate of apparent movement of the target increased approximately linearly. With binaural, bipolar stimulation, the illusory movement of the target was toward the site of the cathode and the threshold decreased by 1.5–2.5 times. With binaural, monopolar stimulation, the target seemed to shift along the vertical and the threshold current was 1.4–3.0 mA. Eye movement appeared at substantially higher currents than those resulting in apparent movement of the target. It is suggested that visual illusions are linked not to vestibular eye-movement reactions, but to the effect vestibular signals have on the spatial perception system.Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 3, pp. 321–327, May–June, 1991.     

The ventromedial nucleus of the hypothalamus and the hormonal arousal of sexual behaviors in the female rat

Bilateral lesions of the ventromedial nucleus of the hypothalamus interfered with the estrogenic induction of sexual receptivity in the female rat, but seemingly did not affect the ability of female rats to show lordosis following combined stimulation with estrogen and progesterone. In addition, ventromedial hypothalamic lesions did not affect the ability of females to show male-like sexual activity in response to exogenous androgenic stimulation.     

Differential Modulation of Corticospinal Excitability by Different Current Densities of Anodal Transcranial Direct Current Stimulation

Background

Novel non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been developed in recent years. TDCS-induced corticospinal excitability changes depend on two important factors current intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set.

Objective/hypothesis

The current study aimed to investigate the effects of four different anodal tDCS (a-tDCS) current densities on corticospinal excitability.

Methods

Four current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs) of 0.013, 0.029, 0.058 and 0.083 mA/cm² were applied on twelve right-handed (mean age 34.5±10.32 yrs) healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm² respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR) was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter.

Results

Post hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm² and 0.029 mA/cm² (P = 0.003). There were no significant differences between excitability changes for the 0.013 mA/cm² and 0.058 mA/cm² (P = 0.080) or 0.013 mA/cm² and 0.083 mA/cm² (P = 0.484) conditions.

Conclusion

This study found that a-tDCS with a current density of 0.013 mA/cm² induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm². The implication is that might help to avoid applying unwanted amount of current to the cortical areas.     

Differentiated pressor and sympathetic responses to dual brain stimulation: ventromedial hypothalamus versus locus coeruleus

Sensitivity of the ventromedial hypothalamus (VMH) to electrical stimulation was compared with that of the locus coeruleus (LC) in urethane-anesthetized rats. Based not only on current strengths required to elicit threshold effects, but also on magnitude of pressor responses to suprathreshold stimulation, the LC was consistently more sensitive than the VMH. Despite this greater pressor sensitivity, splanchnic nerve firing increased almost equally upon stimulation of either brain area. Similar comparisons made in other rats following bilateral adrenalectomy or pretreatment with a vasopressin antagonist showed no significant alteration of pressor and sympathetic responsiveness to stimulation of either the LC or the VMH. When frequency of neural firing was recorded from a lumbar sympathetic trunk instead of the splanchnic nerve, increases in sympathetic nerve activity produced by LC stimulation were significantly larger than those produced from the VMH. The results suggest that greater pressor sensitivity of the LC is due, at least in part, to stronger constriction in vascular beds innervated by the lumbar sympathetic chains.     

The effect of gastric electrical stimulation on canine gastric slow waves

This study determined the most efficient parameters of low-frequency/long-pulse gastric electrical stimulation (GES) required to entrain gastric slow waves and also evaluated the effect of entrainment and high-frequency, short-pulse GES on gastric electrical activity (GEA). Nine dogs were fitted with stimulation wires along the greater curvature. Entrainment was observed in six or seven animals, with long-pulse GES at six cycles per minute (cpm), at various combinations of current and pulse width and was directly related to the energy delivered. Entrainment was observed in four to seven animals, with GES at 12 cpm, and the maximal driven frequency was 6 cpm. Entrainment did not significantly increase the dominant power of GEA. High-frequency, short-pulse GES, using pulse trains of 14 Hz, 5 mA, and 330 micros, with 0.1 s on and 5 s off, and pulse trains of 40 Hz, 10 mA, and 330 micros, with 2 s on 3 s off, did not affect variables of GEA. We conclude that acute low-frequency GES but not high-frequency, short-pulse GES can entrain slow waves; the power of slow waves is not affected by either type of stimulation.     

Muscarinic Modulation of Purine Release from Electrically Stimulated Rat Cortical Slices

The release of 3H-labeled purines at rest and during electrical stimulation was investigated in slices of rat cortex prelabeled with [3H]adenine and perfused with Krebs solution. A linear relationship was found between radioactivity efflux and stimulation frequency from 2.5 to 20 Hz. At frequencies of less than 2.5 Hz, no increase in radioactivity efflux was detected. The amount of tritium released per pulse increased with stimulation frequency up to 10 Hz and declined at 20 Hz. The tritium efflux from the slices at rest and at a stimulation frequency of 10 Hz, analyzed by HPLC with ultraviolet absorbance detection at 254 nm, consisted mostly of adenosine, inosine, and hypoxanthine. The 3H-labeled purine release evoked by 10-Hz stimulation increased with current intensity from 15 to 100 mA/cm2. At 20 mA/cm2, addition of 0.5 microM tetrodotoxin to the superfusing Krebs solution brought about a 98% decrease of 3H-labeled purine release. At higher current strength, the percentage of tetrodotoxin-sensitive-evoked tritium efflux was smaller. At 30 mA/cm2, 86% of the evoked release was tetrodotoxin sensitive. Under these stimulation conditions, tritium efflux showed a 69% decrease when the slices were superfused with calcium-free Krebs solution containing 0.5 mM EGTA. The muscarinic agonist oxotremorine (30 microM) significantly enhanced the 10-Hz-stimulated 3H-labeled purine release. The effect of oxotremorine was partially prevented by tetrodotoxin, was antagonized by atropine (1.5 microM), and was mimicked by addition of physostigmine (3.8 microM) to the superfusion fluid. Atropine alone did not affect the evoked release, and none of the drugs modified the basal tritium efflux.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are Participants Aware of the Type and Intensity of Transcranial Direct Current Stimulation?

Transcranial direct current stimulation (tDCS) is commonly used to alter cortical excitability but no experimental study has yet determined whether human participants are able to distinguish between the different types (anodal, cathodal, and sham) of stimulation. If they can then they are not blind to experimental conditions. We determined whether participants could identify different types of stimulation (anodal, cathodal, and sham) and current strengths after experiencing the sensations of stimulation during current onset and offset (which are associated with the most intense sensations) in Experiment 1 and also with a prolonged period of stimulation in Experiment 2. We first familiarized participants with anodal, cathodal, and sham stimulation at both 1 and 2 mA over either primary motor or visual cortex while their sensitivity to small changes in visual stimuli was assessed. The different stimulation types were then applied for a short (Experiment 1) or extended (Experiment 2) period with participants indicating the type and strength of the stimulation on the basis of the evoked sensations. Participants were able to identify the intensity of stimulation with shorter, but not longer periods, of stimulation at better than chance levels but identification of the different stimulation types was at chance levels. This result suggests that even after exposing participants to stimulation, and ensuring they are fully aware of the existence of a sham condition, they are unable to identify the type of stimulation from transient changes in stimulation intensity or from more prolonged stimulation. Thus participants are able to identify intensity of stimulation but not the type of stimulation.     

Gastrin in the mechanisms of genetic determination of feeding behavior in rabbits

Spreading of a dominant motivation to the molecular intracellular mechanisms of genetic memory was studied. Blockage of protein synthesis in the nervous system selectively abolishes food motivation in rabbits during stimulation of the lateral hypothalamus but exerts no noticeable effect on avoidance responses during stimulation of the ventromedial hypothalamus. During protein synthesis blockage, food motivation returns to normal upon pentagastrin intracerebroventricular (i.c.v.) injection. Intracerebroventricular administration of antigastrin immunoglobulin inhibits feeding reaction to lateral hypothalamic stimulation but not avoidance response to ventromedial hypothalamic stimulation. It was concluded that feeding motivation translates into feeding behavior in the following stages: motivational excitation, gene activation, mRNA synthesis, formation of a gastrin-like peptide, and expression of feeding behavior.     

Dependence of the Magnitude of Postural Reactions in Humans on the Strength of Unilateral Galvanic Anodal and Cathodal Vestibular Stimulations

In 13 healthy volunteers, we recorded stabilographic postural reactions (side inclinations of the body) to unilateral galvanic vestibular stimulation (GVS) by rectangular current pulses (4 sec long, 2, 3, 4, 5, or 6 mA). For the cathodal GVS, the dependence of the magnitude of reaction was linear within this range. The corresponding dependence for the anodal GVS was close to linear at small currents, but the increment of the magnitude became smaller with further increase in the stimulation intensity, and a plateau was formed. A significant divergence between the two curves was observed with stimulation currents 4 mA and higher. This difference can be explained considering modern concepts on the mechanism of GVS-induced effects (an increase or a decrease in the level of tonic impulsation in fibers of the vestibular nerve under the influence of polarization). Anodal GVS continues to suppress tonic activity up to the moment where all GVS-sensitive vestibular afferents stop to generate impulses; a further increase in the intensity of hyperpolarizing current is not accompanied by a decrease in the activity in the vestibular nerve and, consequently, by an increase in the magnitude of postural reactions. The tested approach can be used for qualitative estimation of the vestibular tone in humans. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 169–176, March–April, 2005.     

Influence of renin on the effects of electric stimulation on the ventromedial hypothalamus

The influence of intraventricular injection of different doses of renin on the effects of electrical stimulation of the ventromedial hypothalamus was studied. Injection of renin (10 micrograms/kg) into the lateral ventricles of the brain of experimental animals elicited a prolonged elevation of arterial pressure and a decrease of the heart rate, while given in doses of 20 and 30 micrograms/kg it also provoked arrhythmias and ventricular extrasystoles, and a lowering of the threshold of ventromedial hypothalamus stimulation. It was found that under the central action of renin, a short-term stimulation of the ventromedial hypothalamus provoked ventricular extrasystoles.     

Rethinking Clinical Trials of Transcranial Direct Current Stimulation: Participant and Assessor Blinding Is Inadequate at Intensities of 2mA

Background

Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding.

Methods

A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation.

Results

tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding.

Conclusions

Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.     

Effect of sympathectomy and demedullation on increased myenteric and dorsal vagal complex Fos-like immunoreactivity by cholecystokinin-8

Chemical sympathectomy with daily, intraperitoneal (IP) injections of guanethidine sulfate to adult rats, attenuated myenteric, but not dorsal vagal complex (DVC) Fos-like immunoreactivity (Fos-LI) by cholecystokinin-8 (CCK). This technique destroys only 60-70% of the sympathetic neurons, and spares the hormonal source of catecholamines, the adrenal medulla. The goal of the current study is to evaluate the effect of complete sympathectomy or destroying 100% of the sympathetic neurons by injecting guanethidine to 1-day-old pups (40 mg/kg daily for 5 weeks), and surgically removing the adrenal medulla. In the DVC, demedullation and sympathectomy-demedullation increased Fos-LI by CCK in the area postrema and nucleus of the solitary tract, but sympathectomy-demedullation increased it only in the area postrema. In the myenteric plexus, sympathectomy increased this response in the duodenum, and demedullation increased it in the duodenum and jejunum. On the other hand, sympathectomy-demedullation attenuated myenteric Fos-LI in the jejunum. These results indicate that catecholamines may play an inhibitory role on the activation of the DVC neurons by CCK. In the myenteric neurons, however, catecholamines may have both inhibitory and excitatory roles depending on the level of the intestine e.g., duodenum vs. jejunum. This may also indicate that CCK activates the enteric neurons by different mechanisms or through different pathways.     

Role of atrial fibrillation threshold evaluation on guiding treatment

Atrial fibrillation could be induced reproducibly by 50 Hz rapid stimulation which was given through systolic and early diastolic phase of atrial excitation. Duration of atrial fibrillation induced in this way was roughly dependent on the current amplitude of the stimulation. The minimum current that could induce long-lasting atrial fibrillation (30 sec in the clinical setting, 2 sec in the rabbit or rat model) was defined as atrial fibrillation threshold (AFT). AFT was larger in patients who had history of atrial fibrillation than those who did not. Anti-arrhythmic drugs raised AFT by various degrees both in experimental and clinical cases. Long-term efficacy of a drug could be predicted in a patient, measuring how much the drug increased AFT (cut-off point = 5 mA increase). AFT is a useful marker to evaluate atrial vulnerability and to guide pharmacological treatment of atrial fibrillation.     

Participation of adrenal hormones in the genesis of arterial hypertension of hypothalamic origin]

Continuous many-hour stimulation of the hypothalamic negative emotiogenic centres (ventromedial nuclei) evoked a stable arterial hypertension with a peculiar phasic dynamics of the adrenal secretory activity in waking immobilized rabbits. Bilateral extirpation of the adrenal glands decreased the initial level of the average arterial pressure, inhibiting development of stable arterial hypertension. Many-hour stimulation of the mentioned structures also produced stable arterial hypertension in adrenalectomized rabbits if preceded by the administration of hydrocortisone together with adrenaline. Against the background of separate administration of hydrocortisone and adrenaline to adrenalectomized rabbits, many-hour stimulation of the ventromedial hypothalamus evoked a short-term rise in the arterial pressure. A conclusion was drawn that activation of hormones of the adrenal cortical and medullary layers played an important part in the formation of stable arterial hypertension in rabbits under continuous many-hour stimulation of the hypothalamic negative emotiogenic centres.     

Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat

Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-OHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system.     

Effect of direct electric current on the cell surface properties of phenol-degrading bacteria

The change in cell surface properties in the presence of electric currents is of critical concern when the potential to manipulate bacterial movement with electric fields is evaluated. In this study, the effects of different direct electric currents on the cell surface properties involved in bacterial adhesion were investigated by using a mixed phenol-degrading bacterial culture in the exponential growth phase. The traits investigated were surface hydrophobicity (measured by adherence to n-octane), net surface electrostatic charge (determined by measurement of the zeta potential), and the cell surface shape and polymers (determined by scanning electron microscope analysis). The results showed that a lower current (less than 20 mA) induced no significant changes in the surface properties of phenol-degrading bacteria, that an electric current of 20 mA could increase the surface hydrophobicity and flatten the cell shape, and that a higher current (40 mA) could increase the surface extracellular substances and the net negative surface electrostatic charge. The results also revealed that the electric current effects on cell hydrophobicity varied with the suspending medium. We suggest that an electric current greater than 20 mA is not suitable for use in manipulation of the movement of the phenol-degrading bacteria, although such a current might favor the electrophoretic movement of the bacterial species.