Effects of hypogastric nerve and sympathetic chain stimulation on the pelvic nerve induced penile erection in the dog

The effects of electrical stimulation of hypogastric nerve and sympathetic chain on 'electroerection' (penile erection induced by electrical stimulation of the pelvic nerve) were studied in dogs to clarify the physiological roles that these neural inputs may play in producing and/or maintaining penile erection. As an objective parameter of hemodynamics of the penile circulation, the pressure in the corpus cavernosum of the penis was measured. Hypogastric nerve electrostimulation was performed in 24 dogs who had received pelvic nerve stimulation and, therefore, had 'electroerection'. Ten dogs responded to this procedure with an augmentation of 'electroerection', 10 with an attenuation of 'electroerection', and 4 with no appreciable changes. 4 out of the 10 animals who exhibited an attenuation response were then given an alpha 1-adrenergic blocker (prazosin hydrochloride) prior to the electrical stimulation to evaluate the specificity of the effects of the hypogastric nerve stimulation. In 3 of the 4 dogs the attenuation effect was abolished by this treatment and instead an augmentation effect became evident. Sympathetic chain electrostimulation was performed in 6 dogs with 'electroerection'. When applied to the L4-5 interganglionic segment, it produced a biphasic response which consisted of an initial increase followed by a decrease of the intracorporeal pressure. In contrast, stimulation of the L2-3 interganglionic segment produced a monophasic response consisting of only augmentation of the intracorporeal pressure. These data suggested that there might be two groups of fibers in the hypogastric nerve and sympathetic chain which are functioning antagonistically, and that the anti-erectile neural inputs are mediated primarily by the alpha 1-adrenergic system. To examine the sites of penile vasculature where the innervating hypogastric nerve exerts its effects, electrical pelvic/hypogastric nerve stimulations were performed in dogs in whom the inflow blood circulation to the corpora cavernosa was disrupted by arterial ligation and replaced by a constant saline infusion. It appears that the stimulatory input via the hypogastric nerve caused an increased blood flow into the cavernous space due to vasodilation of the inflow blood vessels, and the inhibitory effect occurred mainly due to relaxation of the draining blood vessels with a resultant increase of the blood outflow from the cavernous space.     

Effect of diltiazem and pinacidil on the response of the rabbit urinary bladder to repetitive stimulation and in vitro ischemia

The effect of repetitive stimulation, in the presence and absence of diltiazem or pinacidil, on the contractile responses of isolated strips of rabbit bladder detrusor to field stimulation and carbachol, after 2 hr of incubation in a medium that serves as an in vitro model of ischemia (oxygen and substrate depleted Tyrode's solution), was determined. Our results are summarized as follows: a) The magnitude of the contractile dysfunctions after in vitro ischemia was enhanced by repetitive stimulation. b) Pre-incubation of isolated strips of detrusor with diltiazem (50 microM) inhibited the contractile responses to field stimulation (FS) and carbachol by 43 and 50%, respectively. Pinacidil (100 microM) inhibited the contractile responses to FS and carbachol by 37 and 32%, respectively. c) Neither diltiazem nor pinacidil protected the bladder strips against the effects of 2 hr of incubation in in vitro ischemia medium. However, d) both pinacidil and diltiazem reduced the level of contractile dysfunctions induced by repetitive stimulation. In conclusion, the contractile response to FS was significantly more sensitive to in vitro ischemia and repetitive stimulation than was the contractile response to carbachol. Both diltiazem and pinacidil protected the contractile responses to FS and carbachol from the degenerative effects of repetitive stimulation, but not from the effects of in vitro ischemia.     

Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain

The effects of diazepam, which acts at GABAA receptors to enhance the effects of GABA, and ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, on local rates of cerebral glucose utilization (ICMRglc) were examined in unrestrained rats. Four groups were studied: vehicle-injected controls; and ketamine-treated, diazepam-treated and combined ketamine- and diazepam-treated animals. Ketamine alone produced a heterogeneous pattern of changes in ICMRglc (e.g. significant increases in the corpus callosum, olfactory tubercle and the entire Papez circuit, in addition to other limbic areas, and significant decreases in lateral habenula and some components of the auditory system). Diazepam alone statistically significantly decreased ICMRglc in the brain as a whole and in most areas of the cerebral cortex, thalamus and limbic system. The most remarkable effects of the two drugs administered together on ICMRglc occurred in the limbic system where the dramatic increases observed with ketamine alone were prevented by treatment with diazepam.      

Ipsilateral pallidal control on the sternocleidomastoid muscle in cats: relationship to the side of thalamotomy for torticollis.

To elucidate the role of the basal ganglia on neck movement control and thus clarify the side of targets for stereotactic surgery of spasmodic torticollis, effects of electrical stimulation to the globus pallidus-entopeduncular nucleus complex (GP-EP) upon the activities of the sternocleidomastoid (SCM) muscle motoneurons were studied in cats. Repetitive stimulation of the ipsilateral GP-EP increased discharge rate in the majority of the SCM motoneurons, whereas contralateral GP-EP stimulation caused a decrease in discharge rate. These effects were gradually enhanced in the course of repetitive stimulation and lasted even after its cessation. Bilateral ablation of the motor and premotor cortices did not influence the effects of GP-EP stimulation. Latency studies suggested that the pallidal control of the SCM motoneuron is mediated by polysynaptic pathways on both sides; however, these same studies produced evidence of an ipsilateral oligosynaptic connection, as well. Repetitive antidromic stimulation of the accessory nerve caused a gradual increase in discharge rate of the SCM motoneurons, similar to the augmentation induced by ipsilateral GP-EP stimulation. Features of the responses indicate that the pallidal control on the neck muscles involves reverberating circuits in the brain stem and spinal cord. These experimental findings suggest that stereotactic thalamotomy of the ventrolateral nucleus for spasmodic torticollis should be performed on the side ipsilateral to the contracting SCM muscle.     

Magnetic stimulation of the sacral roots for the treatment of stress incontinence: an investigational study and placebo controlled trial

PURPOSE: We designed an investigational study and placebo controlled trial to evaluate the potential efficacy of magnetic stimulation of the sacral roots for the treatment of stress incontinence. MATERIALS AND METHODS: A total of 75 patients with stress incontinence were studied. A 15 Hz. repetitive magnetic stimulation of the sacral roots with 50% intensity output and duration of 5 seconds per minute was applied for 30 minutes. Urodynamic investigations under magnetic stimulation were performed in 13 patients to evaluate acute effects to lower urinary tract function. There were 62 women (mean age 58 years) enrolled in a placebo controlled study to investigate the short-term efficacy of magnetic stimulation. The number of leaks for 3 days, amount of urine loss on a pad test and quality of life score were evaluated before and 1 week after stimulation. RESULTS: The urodynamic investigations revealed an apparent elevation of urethral closure pressure induced by stimulation (mean 8.2 +/- 3.0 cm H2O, p = 0.0000004) and a significant increase in bladder capacity after stimulation (mean 40.0 +/- 51.0 ml., p = 0.0152). In the placebo controlled study the number of leaks and amount of urine loss on a pad test significantly decreased more in the active than in the sham stimulation group (p = 0.0023 and 0.0377, respectively). The quality of life score significantly improved in the active stimulation group (p = 0.0006) in contrast to no significant improvement in the sham stimulation group. The improvement rate in the active stimulation group was 74%, which was significantly higher than the 32% in the sham stimulation group (p = 0.0009). No adverse effects were noted in any patients. CONCLUSIONS: These results suggest that magnetic stimulation of the sacral roots may be useful for the treatment of stress incontinence. Further studies are needed to evaluate the long-term efficacy of this potential treatment.     

A rat model for studying effects of sacral neuromodulation on the contractile activity of a chronically inflamed bladder

OBJECTIVE: To develop an animal model in which the effects of electrical stimulation of the sacral nerves (sacral neuromodulation) on a chronic hyperactive urinary bladder can be studied. MATERIALS AND METHODS: In female rats the urinary bladder was instilled with mustard oil (0.4%); after 10 days the animals were anaesthetized with intraperitoneal urethane, the bladder catheterized and connected to a pressure transducer. Stimulating electrodes were placed into the sacral foramina bilaterally. The intensity and duration of sacral electrical stimulation was varied systematically to determine the effects of the sacral neuromodulation on bladder contractions. RESULTS: The main effect of the neuromodulation was an increase in the interval between contractions, i.e. during and for some time after the stimulation the contractions were completely abolished. The duration of the pause increased with the intensity and duration of stimulation. After the contractions had reappeared the frequency of contractions was reduced for a long period. In animals with chronic cystitis the effects of neuromodulation tended to be stronger (the pauses were longer) than in control animals with an intact bladder, but only in one test (increase of pause length with stimulus duration) was the difference statistically significant. CONCLUSIONS: The results show that this animal model is suitable for studying the effects and mechanisms of sacral neuromodulation on a chronic hyperactive urinary bladder.     

Long-term potentiation of polysynaptic responses in layer V of the sensorimotor cortex induced by theta-patterned tetanization in the awake rat

Although the neocortex in awake, adult animals is resistant to the induction of long-term potentiation (LTP), synaptic potentiation may be enhanced by rhythmic patterns of activation that evoke short- term synaptic facilitation effects. The effectiveness of stimulation patterned after the theta (4-12 Hz) EEG rhythm for the induction of LTP of sensorimotor cortex responses to corpus callosum stimulation was assessed in vivo by inducing LTP using either high- frequency (300 Hz) trains or paired trains delivered at a 100 ms (10 Hz) interval. High-frequency trains caused a reduction of the early field potential component, reflecting a potentiation of direct layer V activation, and a potentiation of the late component, reflecting enhanced polysynaptic activation in layer V. Paired trains resulted in a much larger potentiation of polysynaptic responses than was observed following 300 Hz trains. To determine if short-term facilitation effects contributed to the enhanced LTP induction by theta-patterned trains, facilitation effects induced by the trains were challenged with NMDA receptor antagonists. NMDA-receptor antagonism reduced responses to single pulses, and also reduced facilitated responses evoked by theta-patterned stimulation. The effectiveness of theta-patterned stimulation for the induction of LTP of layer V polysynaptic responses is therefore likely due to frequency-dependent synaptic facilitation effects that enhance NMDA receptor activation.     

Discontinuous long-train stimulation in the anterior striatum in monkeys induces abnormal behavioral states

The striatum has been identified as a new target for therapeutic deep brain stimulation in the treatment of neurological and psychiatric disorders. The nonhuman primate model offers opportunities for detailed mapping of the behavioral effects of stimulation within the striatum. We recently showed that dysfunction in the dorsal and ventral striatum was able to produce a specific pattern of abnormal movements and behavioral states. In the present study, electrical stimulation of monkey striatum evoked abnormal movements and behavioral states depending not only on the location of stimulation sites but also on the parameters of stimulation. Abnormal movements were induced by stimulation of sites in the anterior associative and posterior sensorimotor striatum. Short-train stimulation evoked myoclonic-like movements and long-train stimulation produced sustained dystonic-like and complex abnormal movements. Long-train stimulation of the anterior part of the striatum, corresponding to the associative-limbic territory, induced 3 abnormal behavioral states--hyperactivity, hypoactivity, and stereotyped behaviors. Short-train stimulation was less effective in producing these effects. No significant effects were observed with the continuous mode of stimulation. Our results show that discontinuous long-train stimulation of the anterior associative and limbic parts of the striatum is the most effective mode of stimulation to produce these behavioral states.     

Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease

OBJECT: The authors compared the effects of deep brain stimulation (DBS) in the globus pallidus internus (GPi) with those in the subthalamic nucleus (STN) in patients with Parkinson disease (PD) in whom electrodes had been bilaterally implanted in both targets. METHODS: Eight of 14 patients with advanced PD in whom electrodes had been implanted bilaterally in both the GPi and STN for DBS were selected on the basis of optimal DBS effects and were studied 2 months postsurgery in off- and on-stimulus conditions and after at least 1 month of pharmacological withdrawal. Subcutaneous administration of an apomorphine test dose (0.04 mg/kg) was also performed in both conditions. Compared with the off status, the results showed less reduction in the Unified PD Rating Scale Section III scores during DBS in the GPi (43.1%) than during DBS of the STN (54.5%) or DBS of both the STN and GPi (57.1%). The difference between the effects of DBS in the GPi compared with that in the STN or simultaneous DBS was statistically significant (p < 0.01). In contrast, no statistical difference was found between DBS in the STN and simultaneous DBS in the STN and GPi (p < 0.9). The improvement induced by adding apomorphine administration to DBS was similar in all three stimulus modalities. The abnormal involuntary movements (AIMs) induced by apomorphine were almost abolished by DBS of the GPi, but were not affected by stimulation of the STN. The simultaneous stimulation of STN and GPi produced both antiparkinsonian and anti-AIM effects. CONCLUSIONS: The improvement of parkinsonian symptoms during stimulation of the GPi, STN, and both nuclei simultaneously may indicate a similar DBS mechanism for both nuclei in inducing antiparkinsonian effects, although STN is more effective. The antidyskinetic effects produced only by DBS of the GPi, with or without STN, may indicate different mechanisms for the antidyskinetic and antiparkinsonian activity related to DBS of the GPi or an additional mechanism in the GPi. These findings indicate that implantation of double electrodes for DBS should not be proposed as a routine procedure, but could be considered as a possible subsequent choice if electrode implantation for DBS of the STN does not control AIMs.     

Deep brain stimulation for Parkinson's disease: how to select candidates for pallidal or subthalamic stimulation

Chronic deep brain stimulation therapy has the reversibility, selectivity and adjustability needed to achieve an adequate effect, so that it represents an ideal tool for functional neurosurgery designed to treat parkinsonian symptoms. Some kinds of chronic stimulation have become an alternative to lesion-making surgery, supported by the fact that high-frequency stimulation induces quite a small area of inactivity around the stimulating electrode compared with the lesions induced with a lesion-maker, and stimulation directed at a particular target exerts more specific effects on particular symptoms of Parkinson's disease (PD). Thus, whenever stimulation therapy is to be applied to patients, an effective stimulation target must be selected depending on the nature of the symptom to be improved. For example, ventral intermediate nucleus (VIM) thalamic stimulation is able to stop tremor completely, but has no appreciable effects on other symptoms. Bilateral globus pallidum interna (GPi) stimulation and subthalamic nucleus (STN) stimulation have been applied to reduce the pathological inhibitory effects on the thalamocortical circuit from the GPi and/or the substantia nigra pars reticular nucleus (SNr), which produces the final output of the basal ganglia circuits. However, there is still controversy about both the indications for and the role of GPi versus STN stimulation. This article presents a review of recent reports that describe follow-up results and double-blind studies on the signs for relief of each type of parkinsonian symptom, following GPi or STN stimulation. It also includes a discussion of how further research should be organized in order to identify whether GPi or STN stimulation exerts the greatest effect on particular kinds of parkinsonian symptoms.     

Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter.

Electrical stimulation of the periventricular gray matter is an effective means of relieving several types of pain without destruction of neural tissue. The effects are long lasting, often bilateral, and with judicious use do not appear subject to adaptation. However, sustained uninterrupted stimulation for several hours does lead to a reversible decrease in effectiveness. Side effects from stimulation are minimal and cause little or no untoward emotional changes. The results are discussed in terms of activation of an endogenous pain inhibitory mechanism that involves naturally occurring opiate-like factors such as the enkephalins and endorphins.     

Motor evoked potentials for the determination of experimental spinal cord injuries]

In testing the clinical use of motor evoked potentials (MEP), optimal responses were obtained while using a stimulus with an intensity of 1100 V. The studies of spinal cord lesion revealed that MEP was dependent primarily on anterolateral column pathways. MEP was shown to be produced in the muscle and was not the result of volume conduction. On the spinal cord injury, the studies revealed that MEP was a reliable indicator of the initial extent of injuries. No adverse effects from transcranial stimulation were identified by either histological examination of animal brains or EEG after stimulation of animal. During neurosurgery, motor evoked potentials can be use for monitoring and also for detecting the effects of different drugs in treating spinal cord injury.     

Regional differences in the pattern of neurogenic responses in the aganglionic colon from congenitally aganglionic rats

The pattern of innervation in the aganglionic colon and internal anal sphincter from cogenitally aganglionic rats was studied and compared with that of control littermates. In normoganglionic colon and anal sphincter, electrical stimulation evoked excitatory or inhibitory junction potentials followed by a contraction or relaxation, respectively. These responses were abolished by tetrodotoxin and atropine selectively abolished the excitatory effects, indicating that the colon or anal sphincter is innervated by intrinsic cholinergic excitatory and noncholinergic inhibitory nerves. In congenitally aganglionic rats, electrical stimulation evoked excitatory and inhibitory responses in sphincteric regions, while only excitatory responses were observed in distal segments. Excitatory responses were weak in proximal segments of the aganglionic colon and electrical stimulation failed to evoke neurogenic responses. These results indicate regional differences in the functional innervation of extrinsic nerve fibers in the aganglionic colon from congenitally aganglionic rats and the usefulness of congenitally aganglionic rats as an animal model for Hirschsprung's disease.     

Splanchnic neural regulation of insulin and glucagon secretion in the isolated perfused human pancreas

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence or absence of selective neural blockers. The insulin and glucagon responses to hyperglycemia alone or in the presence of splanchnic nerve stimulation were similar in magnitude to the results obtained in a preliminary report on isolated human pancreatic function and in studies using animal models. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in an inhibition of insulin release and in an augmentation of glucagon release. alpha-adrenergic stimulation resulted in a strong suppression of insulin secretion and a mild suppression of glucagon secretion. beta-adrenergic fiber stimulation caused a mild augmentation of both insulin and glucagon release, whereas the cholinergic fibers strongly stimulated both alpha- and beta-cell secretion. The predominant effects of celiac neural bundle stimulation are insulin inhibition by was of an alpha-adrenergic effect and glucagon stimulation by way of a cholinergic effect. Thus, in this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role on pancreatic hormone release in human subjects.     

Deep brain stimulation for Parkinson’s disease: how to select candidates for pallidal or subthalamic stimulation

Chronic deep brain stimulation therapy has the reversibility, selectivity and adjustability needed to achieve an adequate effect, so that it represents an ideal tool for functional neurosurgery designed to treat parkinsonian symptoms. Some kinds of chronic stimulation have become an alternative to lesion-making surgery, supported by the fact that high-frequency stimulation induces quite a small area of inactivity around the stimulating electrode compared with the lesions induced with a lesionmaker, and stimulation directed at a particular target exerts more specific effects on particular symptoms of Parkinson’s disease (PD). Thus, whenever stimulation therapy is to be applied to patients, an effective stimulation target must be selected depending on the nature of the symptom to be improved. For example, ventral intermediate nucleus (VIM) thalamic stimulation is able to stop tremor completely, but has no appreciable effects on other symptoms. Bilateral globus pallidum interna (GPi) stimulation and subthalamic nucleus (STN) stimulation have been applied to reduce the pathological inhibitory effects on the thalamocortical circuit from the GPi and/or the substantia nigra pars reticular nucleus (SNr), which produces the final output of the basal ganglia circuits. However, there is still controversy about both the indications for and the role of GPi versus STN stimulation. This article presents a review of recent reports that describe follow-up results and double-blind studies on the signs for relief of each type of parkinsonian symptom, following GPi or STN stimulation. It also includes a discussion of how further research should be organized in order to identify whether GPi or STN stimulation exerts the greatest effect on particular kinds of parkinsonian symptoms.     

Alpha-adrenoceptor stimulation in the presence of halothane: effects on impulse propagation in cardiac Purkinje fibers;.

Halothane effects on action potential characteristics and conduction were determined in canine Purkinje fibers, before and during alpha-adrenergic stimulation. Halothane significantly decreased effective refractory period and action potential duration in Purkinje fibers. alpha-Adrenergic stimulation restored effective refractory period and action potential duration in Purkinje fibers exposed to halothane via an alpha 1-adrenoceptor mediated effect antagonized by prazosin. Halothane significantly slowed propagation of impulses initiated at a basic cycle length of 500 ms, and conduction of premature impulses, in Purkinje fibers. In the presence of halothane, alpha-adrenergic stimulation had no additional effects on normal impulse propagation; however, alpha-adrenergic stimulation significantly slowed the conduction of premature impulses in Purkinje fibers exposed to halothane. These data refute a previous report that alpha-adrenergic stimulation enhances halothane's negative dromotropic effect in Purkinje fibers paced at a basic drive cycle length. alpha-Adrenergic prolongation of the conduction times of premature stimuli in Purkinje fibers exposed to halothane is a new finding.     

The mechanism and effect of chronic electrical stimulation of the globus pallidus for treatment of Parkinson disease

OBJECT: Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. METHODS: Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as gamma-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. CONCLUSIONS: Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.     

Chronic electric stimulation of the internal globus pallidus and subthalamic nucleus in Parkinson disease

PATHOPHYSIOLOGY: In Parkinson's disease, the neurodegenerative process of the nigrostriatal dopaminergic pathways induces an increase in activity of the subthalamic nucleus and the medial globus pallidus, which cause inhibition of thalamo-cortical outputs explaining parkinsonism. HIGH-FREQUENCY DEEP BRAIN STIMULATION: The adverse effects induced by lesions of subcortical structures (thalamotomy, pallidotomy) have increased interest in chronic electrical stimulation proposed as a new therapy in Parkinson's disease. This technique is reversible and can be modulated with less adverse effects. TWO TARGETS: Two targets may be proposed in case of severe motor fluctuations: the medial globus pallidus and the subthalamic nucleus. Pallidial stimulation improves dramatically levodopa-induced dyskinesia and, with a variable degree, the parkinsonian triad. Subthalamic stimulation rapidly reverses akinesia, rigidity and tremor and also dyskinesias which progressively tend to diminish after decreasing L-dopa dosage. LONG-TERM EFFICACY: A follow-up period of a few years has confirmed that the beneficial effect is maintained. However, stimulation dose not prevent the development of certain symptoms (postural impairment, cognitive decline). LIMITED INDICATIONS: Chronic electrical stimulation of medial globus pallidus and subthalamic nucleus may be proposed for parkinsonian patients with severe motor fluctuations associated with abnormal involuntary movements which are not controlled by different medical therapies. Parkinsonian symptoms must still be levodopa responsive and cause severe clinical disability severely limiting daily living activities. Cognitive impairment and other severe pathologies are contraindications.     

Effect of aminoglycoside antibiotics on the electrical stimulation-induced contractile response of the guinea-pig ureter

Using electrical stimulation, we first investigated whether the movement of ureteral smooth muscle of the guinea-pig was myogenic in its control, or neurogenic. We then investigated the effects of aminoglycoside antibiotics (kanamycin, bekanamycin and ribostamycin) on the movement of ureteral smooth muscle induced by electrical stimulation. In these investigations, each ureter removed from the animal was cut into three approximately equal-sized segments, which are an upper segment (kidney side), a middle segment and a lower segment (urinary bladder side). Each segment was mounted in an organ bath filled with Krebs solution and the mechanical response induced by electrical stimulation of each segment was recorded isometrically. Each one of the upper, the middle and the lower segments was stimulated with rectangular pulses (50 volt, 0.1-3 msec durations, 40 Hz) for a period of 2 sec. Of all segments tested (ten in each group), none showed any response to the stimulation with pulses below 0.5 msec duration. While 2-3 segments out of ten of the upper, the middle and the lower ureteral segments showed a contractile response to stimulation with pulses of 1 msec duration, the rest of the segments showed no response to the same stimulation. This contractile response was not inhibited by tetrodotoxin which is known to block the nerve-mediated response. And also, all the ten samples of each upper, middle and lower segment never failed to show a contractile response to stimulation with pulses of 2 msec and 3 msec duration. Various drugs which are already known to block the nerve-mediated response (i.e., atropine, guanethidine, phentolamine, propranolol and tetrodotoxin) were tried, but none of them had an inhibitory effect on the contractile response. On the other hand, each one of kanamycin (KM), bekanamycin (AKM) and ribostamycin (RSM) in concentrations of 1 x 10(-5) g/ml-1 x 10(-3) g/ml produced a concentration-dependent decreasing effect in the magnitude of the electrical stimulation-induced contractile response of the ureteral segment. In addition, the decreasing effects of these antibiotics were also observed in the tetrodotoxin. From these results, we concluded that the contractile response of the ureter may be myogenic in its control, and the aminoglycoside antibiotics, KM, AKM and RSM, may act directly on the ureteral smooth muscle so as to decrease its contractile response.     

Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neurons

OBJECT: The goal of this study was to evaluate the neuroprotective effects conferred by long-term electrical stimulation of the subthalamic nucleus (STN) against degeneration of dopaminergic neurons by assessing motor functional and immunohistological findings in hemiparkinsonian rats. METHODS: In 13 of 25 rats, a concentric microelectrode was stereotactically implanted into the right STN under the guidance of extracellular microelectrode recording. After this had been done the animals were given an injection of 6-hydroxydopamine (6-OHDA) into the right striatum. Seven of the rats received continuous stimulation (frequency 130 Hz, intensity 80-100 microA) for 2 weeks (Group A); the other six did not receive any stimulation during this period (Group B). Twelve rats did not receive electrode implantation and underwent 6-OHDA injection only; these animals served as a control group (Group C). After 2 weeks, motor function in the rats was evaluated by conducting an amphetamine-induced rotation test. Finally, tyrosine hydroxylase-immunoreactive neurons in the pars compacta of the substantia nigra (SNc) were counted to evaluate the extent of degeneration of dopaminergic neurons. Ipsilateral rotation was significantly decreased in Group A, regardless of the effects of stimulation delivered during the test (p < 0.05). Rats in Group B demonstrated typical circling as did those in Group C, except that on stimulation Group B rats immediately stopped circling or changed direction. Tyrosine hydroxylase-immunoreactive neurons in the SNc were significantly preserved in the animals in Group A, whereas neurons in animals in Groups B and C were moderately depleted (p < 0.01). CONCLUSIONS: Acutely, STN stimulation improved rotation symmetry in rats with moderate SNc degeneration. When STN stimulation had been applied for the preceding 2 weeks, motor function was better and SNc neural degeneration was significantly milder. Subthalamic nucleus stimulation thus appears to protect dopaminergic neurons in this hemiparkinsonian model, in addition to improving motor function in these animals.