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PubMed2006

Periurethral injection of sustained release basic fibroblast growth factor improves sphincteric contractility of the rat urethra denervated by botulinum-a toxin.

PURPOSE: We evaluated the effects of sustained release basic fibroblast growth factor injection in rat urethra denervated by botulinum-A toxin (Wako Life Science, Osaka, Japan). MATERIALS AND METHODS: A total of 30 female Sprague-Dawley rats underwent periurethral injection of 10 U botulinum-A toxin to induce chemical denervation of the urethral sphincter. Leak point pressure in the waking state was determined and a significant decrease in leak point pressure vs that in control rats was confirmed (mean +/- SD 58.7 +/- 6.2 vs 120.7 +/- 13.0 cm H(2)O, p <0.0001). Two weeks later 0, 50 and 200 microg basic fibroblast growth factor incorporating 200 microl gelatin hydrogels in 10 rats each were injected into the urethral sphincter, enabling sustained release of basic fibroblast growth factor for 2 weeks. Four weeks later injection leak point pressure measurement and histological evaluation of the urethra were performed. RESULTS: Leak point pressure in rats with 50 and 200 microg basic fibroblast growth factor injection was significantly higher than in rats with the 0 microg injection (82.7 +/- 9.0 vs 95.1 +/- 6.2 and 119.3 +/- 8.1 cm H(2)O, p = 0.0021 and <0.0001, respectively). Maximum cross-sectional area of the urethral smooth muscle layer in the 50 and 200 microg groups significantly increased compared with that in the urethra in the 0 micro group, which was considered 100% (114.1% +/- 15.8% and 132.5% +/- 13.4%, p = 0.029 and <0.0001, respectively). Similarly the cross-sectional area of the striated sphincter in the 50 and 200 microg groups was greater than the 100% in the 0 microg group (112.3% +/- 15.6% and 124.3% +/- 14.1%, p = 0.069 and 0.0007, respectively). Vascular density in the urethral peri-atrophic zone in the 50 and 200 microg groups was significantly higher than in the 0 microg group (p = 0.027 and <0.0001, respectively). CONCLUSIONS: Sustained release basic fibroblast growth factor injection in the chemically denervated urethral sphincter facilitates regeneration of the urethral muscles and improves sphincteric contractility. Endoscopic periurethral injection of basic fibroblast growth factor incorporating gelatin hydrogels may be an attractive therapy for stress urinary incontinence.

Animals↗
PubMed2005

Denervation and repeated L-DOPA induce complex regulatory changes in neurochemical phenotypes of striatal neurons: implication of a dopamine D1-dependent mechanism.

Motor complications induced through repeated L-DOPA treatment in patients with Parkinson's disease are thought to be the consequence of molecular adaptations that occur in response to repeated dopamine receptors stimulation. Here, we studied the molecular changes taking place in the denervated striatum of unilaterally 6-OHDA-lesioned rats repeatedly treated with L-DOPA alone or combined to the D1 receptor antagonist SCH23390. We looked at the territorial patterns of expression of neurotensin (NT), dynorphin (DYN), enkephalin (ENK) and Nur77 (also known as NGFI-B) mRNA expression in the striatum and contrasted these with markers of glutamatergic transport and dopaminergic receptor functions. The denervation process induced NT and Nur77 mRNA expression in ENK-positive cells. Subsequent repeated L-DOPA treatment led to a sensitization of L-DOPA-induced rotational response and produced a second surge of NT induction, this time limited to DYN-positive cells and preferentially restricted to the lateral striatum. In this specific territory, the number of Nur77-positive cells was decreased, in response to L-DOPA, when compared to the medial part of the lesioned striatum. L-DOPA treatment increased dopamine D3 receptor and glutamate transporter 1 (GLT1) mRNA expression in the lesioned striatum and that, specifically in an area overlapping one of Nur77 decrease and of NT/DYN induction. The concomitant administration of SCH23390 with repeated L-DOPA treatment blocked the development of behavioral sensitization and the appearance of all L-DOPA-induced molecular reorganizations reported above. Our results showed that repeated L-DOPA treatment produces, in a denervated striatum, a complex pattern of genes regulation in both the direct and the indirect striatal output pathways. This phenomenon is located preferentially in a striatal area receiving converging inputs from the thalamus and sensorimotor cortex and is dependent upon D1 receptor stimulation.

Animals↗
PubMedDate not supplied

Radiofrequency lumbar facet denervation: a comparative study of the reproducibility of lesion size after 2 current radiofrequency techniques.

BACKGROUND AND OBJECTIVES: Radiofrequency facet denervation procedures are widely used for the treatment of chronic low-back pain. Currently, both temperature-controlled and voltage-controlled techniques are used. In this combined in vivo and in vitro study, the electrophysiologic consequences and the effects on lesion size of these techniques were determined. METHODS: Thirty-three patients were randomly assigned to receive a lumbar radiofrequency facet denervation by using either temperature-controlled (80 degrees C, 60 seconds) or voltage-controlled (20 V, 60 s) mode. Electrophysiologic parameters in both groups during radiofrequency lesioning were registered. Observed differences between electrodes were quantified and interpreted, using lesion-size data from egg-white experiments. RESULTS: Seventeen patients in the temperature group were treated with a total of 55 radiofrequency lesions, all considered technically adequate. In the voltage-controlled group, 16 patients received 63 lesions. Of these, 44 (69.8%) procedures were found to be technically inadequate. Voltage-controlled radiofrequency lesioning resulted in uncontrollable fluctuations of temperature, with resultant uncontrollable variations in lesion size. Temperature-controlled mode created reproducible lesion sizes. CONCLUSIONS: There is no consistent relation between voltage and the temperature obtained during radiofrequency lumbar facet denervation. Temperature-controlled radiofrequency lesioning is preferred to create reproducible lesion sizes.

Adult↗
PubMed2004

Morphometric ultrastructural analysis of satellite cells in denervated rat soleus muscle.

Morphometric analysis of the ultrastructural changes of satellite cells (SCs) of rat soleus muscle 7, 14, and 36 days post denervation was performed. Denervation caused decrease of surface area cross-section of SCs and their nuclei, volume fractions of nucleus and Golgi complex elements and ribosomes number. In contrast, the increase of surface area/volume ratio of SCs and nucleus, volume fraction and number of endosome/lysosome-like structures, and number of caveolae-like structures was noticed. Ultrastructural changes of SCs in denervated muscles strongly suggest decline of cell activity accompanied by increased processes of degradation of material of endo-, and/or egzogenous origin.

Animals↗
PubMed1983

Influence of partial sympathetic denervation on the results of myocardial revascularization in variant angina.

Poor results of the aortocoronary bypass graft operation in the treatment of variant angina have been ascribed to recurrent vasospastic activity due to autonomic imbalance. Cardiac sympathetic denervation (plexectomy) may represent a rational approach in the prevention of vasospasm. To test the value of plexectomy in the treatment of variant angina, 31 patients were studied, 17 of whom (Group 1) underwent conventional coronary artery grafting whereas the remaining 14 (Group 2) underwent cardiac sympathetic denervation also. The 2 groups were similar with respect to age (54 +/- 8 versus 50 +/- 7 years), sex distribution (male/female ratio 12/5 versus 9/5), prevalence of coexisting effort angina (10 versus 12 patients), previous myocardial infarction (7 versus 4 patients), and duration of variant angina (3.3 +/- 5.4 versus 2.4 +/- 2.7 months). The left ventricular ejection fraction was comparable in both groups (60 +/- 11 versus 60 +/- 4%) as were left ventricular end-diastolic pressure (15 +/- 4 versus 13 +/- 5 mm Hg) and extent of coronary artery disease (65 versus 71% prevalence of multivessel disease). The average duration of follow-up was 23 +/- 15 months in Group 1 and 22 +/- 18 months in Group 2 (p = not significant [NS]). There were no operative deaths. Four patients, 2 in each group, had a perioperative myocardial infarction. Seven patients in Group 1 and 1 patient in Group 2 had recurrent variant angina. There was sudden death and 2 infarcts in Group 1. Actuarial curves showed the cumulative probability of recurrent variant angina to be significantly lower (p less than 0.05 and p less than 0.001 at 6 and 10 months, respectively) in Group 2. This study suggests that cardiac sympathetic denervation may prevent recurrent vasospastic activity in variant angina.

Adult↗
PubMed1997

Pulp interstitial fluid pressure and blood flow after denervation and electrical tooth stimulation in the ferret.

The effects of sensory and sympathetic denervation on simultaneously measured interstitial fluid pressure and blood flow in the canine pulp before, during and after electrical tooth stimulation were investigated in 25 ferrets. The micropuncture technique was used to measure interstitial fluid pressure and laser-Doppler flowmetry was used to record pulpal blood flow. Animals with an intact innervation (group 1) served as controls. Sensory denervation was by axotomy of the left inferior alveolar nerve 10 days before the experiment (group 2) and sympathectomy by removal of the left cervical ganglion 5 days before the experiments (group 3). The study was designed to verify whether denervation affected basal pulp blood flow and interstitial fluid pressures during control conditions and/or after tooth stimulation. During control conditions the interstitial fluid pressure averaged 1.32 +/- 0.07 kPa in group 1, whereas the mean was only 0.51 +/- 0.13 kPa in the axotomized animals (group 2). The difference was highly significant, indicating decreased blood or interstitial fluid volume in the pulp after inferior alveolar nerve axotomy. In the sympathectomized group neither the interstitial fluid pressure nor the pulp blood flow was significantly different from those of group 1. Electrical tooth stimulation caused an almost simultaneous increase in interstitial fluid pressure and pulp blood flow in groups 1 and 3, whereas stimulation did not significantly change either variable in the axotomized animals (group 2). It is concluded that a resting nervous vasodilator tone of sensory origin exists in the ferret dental pulp, and that the sensory nerves are responsible for the increased interstitial fluid pressure and pulp blood flow during tooth stimulation.

Animals↗
PubMed1999

Chronic cardiac denervation affects the speed of coronary vascular regulation.

OBJECTIVE: We tested the hypothesis that the rate of adaptation of coronary metabolic vasodilatation and autoregulation is modulated by the cardiac nerves. METHODS: Anaesthetised dogs (seven innervated (control) and seven with denervated hearts) were subjected to controlled pressure perfusion of the left main coronary artery. Heart rate was controlled by pacing. RESULTS: The steady state autoregulation curves and metabolic regulation curves were similar in the two groups. A sudden increase or decrease in heart rate was associated with a faster response (22% shorter half-times) in the innervated than the denervated dogs (P < 0.001). A sudden increase or decrease in coronary arterial perfusion pressure was associated with a slower response (24% longer half-times) in the innervated than the denervated hearts (P < 0.005). CONCLUSIONS: We conclude that the speed of response to metabolic and perfusion pressure changes is partly mediated by cardio-cardiac reflexes. Reflex coronary vasodilatation appears to reinforce the metabolic vasodilatation of a heart rate increase and oppose the vasoconstriction in response to increased perfusion pressure.

Analysis of Variance↗
PubMed1978

Acid phosphatase activity in normal and denervated chick skeletal muscle.

Histochemical and biochemical changes in acid phosphatase activity were studied in the normal and denervated gastrocnemii of chick for a maximum period of 8 weeks. In the normal muscle, fibre heterogeneity with respect muscles exhibit greater susceptibility to degenerative changes on account of denervation. Quantitatively higher enzyme levels in the denervated muscles confirm the lytic role of acid phosphatase.

Acid Phosphatase↗
PubMed2002

Sympathetic denervation-induced changes in G protein expression in enteric neurons of the guinea pig colon.

Chronic sympathetic denervation entails subsensitivity to alpha(2)-adrenoceptor agonists and supersensitivity to kappa- and mu-opioid receptor agonists modulating cholinergic neurons in the guinea pig colon. A possible role for signal transduction G proteins in contributing to development of these sensitivity changes was investigated. Pertussis toxin (PTX), a blocker of the G(i/o)-type family of G proteins significantly reduced the inhibitory effects of UK14,304 (alpha(2)-adrenoceptor agonist), U69593 (kappa-opioid receptor agonist) and DAMGO (mu-opioid receptor agonist) on acetylcholine (ACh) overflow in preparations obtained from normal animals, but not in those obtained from sympathetically denervated animals. In this experimental condition, immunoblot analysis revealed reduced levels of G(alphao), G(alphai2), G(alphai3) and G(beta) in myenteric plexus synaptosomes. On reverse, synaptosomal levels of G(alphai1) and G(alphaz), a PTX-insensitive G-protein, increased after chronic ablation of the sympathetic pathways. These data suggest that changes in the function and expression of inhibitory G proteins coupled to alpha(2)-adrenoceptors, kappa- and mu-opioid receptors occur in the myenteric plexus of the guinea pig colon after chronic sympathetic denervation. The possibility that regulation of G proteins represents one of the biochemical mechanisms at the basis of the changes in sensitivity of enteric cholinergic neurons to alpha(2)-adrenoceptor, kappa- and mu-opioid receptor agonists is discussed.

Acetylcholine↗
PubMed1997

Denervation of pigment cells lead to a receptor that is ultrasensitive to melatonin and noradrenaline.

Pigment granule aggregation and dispersal can be studied in the melanophores of isolated scales from the cuckoo wrasse (Labrus ossifagus L.). Stimulation of a melanophore alpha2-adrenoceptor or the sympathetic nerve innervating the cell causes pigment aggregation. When the stimulation ceases, the pigment granules disperse throughout the cell. Studying this migration has been a useful tool in pharmacological research, particularly in investigations of the alpha2-adrenoceptor. Denervation of melanophores creates a receptor that is ultrasensitive to noradrenaline and melatonin. After three to four weeks of isolation, the denervated melanophores exhibit a 10(9)-fold increase in sensitivity. The efficacy of melatonin is increased from a negligible pigment-aggregation ability to the level of a full agonist. The melatonin-induced aggregation can, however, be counteracted by the alpha2-adrenoceptor antagonist yohimbine, but not by alpha1-adrenoceptor antagonist prazosin, indicating that the ultrasensitive receptor possesses alpha2-adrenoceptor features. Consequently, we conclude that the ultrasensitive receptor may represent an alpha2-adrenoceptor that has, due to denervation of the melanophore, become sensitive to melatonin.

Adrenergic alpha-Agonists↗
PubMed1991

Selective peripheral denervation for torticollis: preliminary results.

Herein we report the preliminary results in nine patients who have undergone selective peripheral denervation for spasmodic torticollis and have been followed up for at least 13 months. All patients had improvement immediately after surgical intervention, and the results have been maintained in five patients. In one patient who had recurrent torticollis, a second procedure in conjunction with injection of botulinum toxin has produced substantial improvement; however, follow-up was brief (6 months). No surgical complications occurred. We believe that selective peripheral denervation is safe and that it can benefit patients with torticollis who have not responded to other types of therapy. These favorable results confirm other published reports on the efficacy of selective peripheral denervation. Long-term follow-up, however, is necessary for determining the role of this procedure in the management of torticollis.

Adult↗
PubMed1988

Vascular reactivity to methoxamine in conscious sinoaortic denervated rats.

Alterations in vascular alpha-adrenoceptor responsiveness following sinoaortic denervation was studied in conscious rats. The arterial hypertension observed in baroreceptor denervated rats decreased progressively during the 30 days of observation. A pressor hyperresponsiveness to methoxamine (10-80 micrograms/kg, iv), was observed 3 to 7 days after baroreceptor denervation followed by a gradual normalization of the vascular reactivity. The results indicate a possible participation of an enhanced alpha 1-adrenoceptor-mediated vasoconstrictor component in the early phase of neurogenic hypertension.

Animals↗
PubMed2002

Frequency responses to hypoxia and hypercapnia in carotid body-denervated conscious rats.

The ventilatory response to brief, severe hypoxia is biphasic consisting of an initial facilitation followed by a slowing of breathing frequency (fR). After the hypoxic stimulus is removed, fR drops below baseline levels. This phenomenon is called the post-hypoxic frequency decline (phfd). These fR changes are due to reciprocal changes in expiratory time (TE), mediated by the ventrolateral pontine A5 region (J. Physiol. (London) 497 (1996) 79; Am. J. Physiol. 274 (1998) R1546). The purpose of this study was to determine if carotid body input is required for full manifestation of phfd by quantifying ventilation in intact and carotid sinus denervated rats in response to hypoxic, and contrasted with hypercapnic stimuli. Following carotid denervation the initial facilitation of fR was eliminated in response to hypoxia, but the phfd remained. In contrast the pattern in response to increased CO2 remained constant before and after carotid denervation. These results suggest that phfd is not dependent upon carotid body stimulation, but is mediated centrally.

Animals↗
PubMed1998

Segmental denervation and reinnervation of the iris sphincter as shown by infrared videographic transillumination.

OBJECTIVE: This study aimed to analyze the denervation and reinnervation history of individual segments of the iris sphincter in patients with Adie's syndrome. DESIGN: The irises of these patients were retroilluminated by shining an infrared-rich light through the lower eyelid and sclera and viewing the transilluminated iris from the front with an infrared-sensitive video camera. The irises of the same group of patients also were videotaped through a slit-lamp camera using routine frontal illumination. Both of these techniques also were used to examine a series of normal subjects. PARTICIPANTS: A total of 61 patients with Adie's syndrome or Adie's-like denervation of the iris sphincter (from surgery, trauma, or radiation) and 10 normal subjects were studied. MAIN OUTCOME MEASURES: Slit-lamp examination results of the segmental movement of the iris were compared to the infrared transillumination pattern of the iris sphincter before and during the light reflex, before and during the near-vision reaction, before and during eye movement, and before and after the application of dilute pilocarpine and 1% pilocarpine. RESULTS: Whenever an iris sphincter segment contracted, it also became denser by using these techniques. Reinnervated iris segments failed to contract to light but did contract and became denser with a near effort or with eye movement. Segments supersensitive to pilocarpine became denser than adjacent segments without supersensitivity, but atrophic-appearing segments looked translucent and thin, failing to become denser, even with 1% pilocarpine. CONCLUSIONS: The innervational history and current status of each clock-hour segment of the iris sphincter can be determined using this technique of videographic infrared transillumination, and the progression and pattern of iris denervation and reinnervation can be determined in patients with Adie's pupil. A miotic Adie's pupil that is "tonic," even in darkness, was found to be associated with a dense pattern of infrared transillumination in sphincter segments, which the authors interpret as being associated with a rich reinnervation from accommodative fibers. Segments that become densely reinnervated appear to lose their cholinergic supersensitivity.

Adie Syndrome↗
PubMed1997

Effect of local autonomic denervation on in vitro responsiveness of lymphocytes from rat submaxillary lymph nodes.

The local autonomic denervation of rat submaxillary lymph nodes was achieved by a unilateral sympathetic superior cervical ganglionectomy and/or the unilateral section of chorda tympani (that resulted in ipsilateral parasympathetic decentralization of the submandibular territory). This study was performed to determine: (1) whether local sympathetic and/or parasympathetic denervation of rat submaxillary lymph nodes brought about changes in lymph node cellularity, natural killer activity and lipopolysaaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation in Freund's adjuvant-injected rats; (2) whether the effect of the immunosuppressive drug cyclosporine in rat submaxillary lymph nodes was affected by a single or combined unilateral ganglionectomy plus decentralization. A unilateral ganglionectomy, or the combination of ganglionectomy plus decentralization, performed 7 days earlier, decreased significantly cellularity in ipsilateral submaxillary lymph nodes, while a unilateral decentralization failed to affect it. Natural killer activity increased ipsilaterally after ganglionectomy or decentralization, and decreased after the combined surgical procedure. LPS-induced cell proliferation augmented significantly after ganglionectomy or decentralization, while Con A-induced T lymphocyte proliferation remained unaffected. In the sham-operated side, cyclosporine decreased submaxillary lymph node cell number and natural killer activity, while it increased the proliferative response to LPS. The depressive effect of cyclosporine on lymph node cellularity was no longer observed in ganglionectomized or decentralized lymph nodes, but was found after the combined surgical denervation. Decentralization, or decentralization plus ganglionectomy, blunted the depressive effect of cyclosporine on natural killer activity. The stimulatory effect of cyclosporine on lymphocyte proliferation induced by LPS was reversed both by ganglionectomy or by decentralization and was suppressed by the combined surgical procedure. Neither treatment affected Con A-induced proliferation of T lymphocytes. The results further indicate that an appropriate sympathetic and parasympathetic local environment may be needed for immunomodulation, as well as for cyclosporine activity in lymphoid tissue.

Animals↗
PubMed2004

Facilitation of motor skill learning by callosal denervation or forced forelimb use in adult rats.

Unilateral forelimb sensorimotor cortex lesions in adult rats produce a compensatory hyper-reliance on the forelimb ipsilateral to the lesion and temporally related glial and neural plasticity in the contralateral homotopic cortex. Recently, we found that these lesions enhance acquisition of a motor skills task with the ipsilateral, non-impaired, forelimb in comparison to shams. This effect might be related to a denervation-induced facilitation of neuroplastic changes in the motor cortex opposite the lesion and/or to the lesion-induced hyper-reliance on the non-impaired forelimb. The present study assessed whether increased forelimb use, denervation of motor cortical callosal afferents, or a combination of the two influences acquisition of a skilled reaching task. Adult rats with partial corpus callosum transections or sham procedures were either forced to rely on one forelimb or permitted normal forelimb use for 8 days. Rats were then trained for 14 days with their previously non-preferred forelimb (and the forced-use limb) on a unilateral pellet retrieval task. Compared to shams, transections produced a greater acquisition rate and asymptotic performance level on the task. Forced-use improved reaching performance relative to controls, but this effect was less enduring than the improvements produced by transections alone. The addition of forced-use to transections did not further enhance performance. These findings suggest that denervation-induced changes are likely to be a major contributor to the enhanced learning observed after unilateral sensorimotor cortex lesions.

Animals↗
PubMed1999

Postoperative hypertension effect of carotid sinus denervation.

Postoperative arterial blood pressures were monitored in 43 patients who had undergone bilateral neck dissection during a 6-week period at Ankara Numune Hospital's IInd Otorhinolaryngology Department. During the first operations, all cases received carotid sinus denervation, whereas no denervation was done for the opposite side dissections held 6 weeks later. Study and control groups were composed of the same patients to achieve an objective outcome for the risk of postoperative hypertension. Hypertension was observed in 10 (23%) of 43 patients after the first operations and 12 (28%) of 43 patients after the opposite side dissections, for which no carotid denervation was done. The difference between the rates was insignificant statistically.

Adult↗
PubMed1997

Renal denervation altered the hemodynamic and renal effects following intracerebroventricular administration of the I1-imidazoline receptor agonist, rilmenidine, in pentobarbital anaesthetized rats.

Previous studies have reported on the effects of intracerebroventricular (icv) administration of the I1-imidazoline receptor agonist moxonidine. In the present study, the relationship between increasing doses of the I1-agonist rilmenidine (administered icv) with blood pressure and renal function has been determined. Moreover, the importance of the renal nerves in this response have also been assessed. In pentobarbitone anesthetized rats, icv rilmenidine (30, 100, 300 nmol in 5 microliters) produced a dose related decrease in blood pressure and heart rate. Urine flow was not altered at the lower doses although at the highest dose (300 nmol) the increase approached significance (p = 0.06). Sodium excretion and osmolar clearance were not altered. Free water clearance was increased at 100 and 300 nmol rilmenidine (p < 0.05). Consistent with the above dose response studies, in sham denervated rats icv rilmenidine (300 nmol) decreased blood pressure and increased free water clearance. In rats having undergone renal denervation, baseline levels of urine flow rate, sodium excretion and osmolar clearance were increased. In these denervated rats, icv rilmenidine (300 nmol) failed to decrease blood pressure. Urine flow rate was increased with a decrease in sodium excretion and osmolar clearance. Free water clearance was increased. These results indicate the importance of the renal nerves in mediating the acute decrease in blood pressure following icv administration of the I1-imidazoline receptor agonist rilmenidine. The increase in free water clearance seen following icv rilmenidine appears to be mediated independent of the renal nerves. The changes associated with sodium excretion on the contrary are dependent on intact renal nerves.

Anesthesia↗