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Denervation
Kinds of Denervation Selected AbstractsEffects of hind limb denervation on the development of appendicular ossicles in the Dwarf African Clawed Frog, Hymenochirus boettgeri (Anura: Pipidae)ACTA ZOOLOGICA, Issue 4 2009Hyoung Tae Kim Abstract Sesamoids and other appendicular ossicles are common in other classes of vertebrates but comparatively rare in amphibians. The pipid frog Hymenochirus boettgeri (Boulenger, G. A. 1899. On Hymenochirus, a new type of aglossal batrachians. , Annals of the Magazine of Natural History Series 7: 122,125) is unusual among anurans in having seven (or more) appendicular ossicles in each hind limb. Sesamoids are often associated with muscles and tendons, and their development is usually regarded as mediated by or correlated with function. This study investigated the effects of paralysis (loss of function) on development of ossicles in the hind limb of Hymenochirus. Complete denervation of the right sciatic nerve was performed at developmental stages 63 and 66, and the animals maintained for a further 6,7 or 12,13 weeks. Specimens were cleared and double stained for cartilage and bone. There were no gross morphological differences between control and sham operated groups. The lunulae were not affected by paralysis, whereas the fabella arose later and/or regressed in some specimens. The distal os sesamoides tarsalia (OST) was shorter in paralysed individuals, and both the distal OST and cartilagines plantares showed delayed maturation. Denervation of the hind limb thus affected the timing of appearance, maintenance and rate of maturation of some sesamoid bones in Hymenochirus, but had no effect on others. [source] Dehydroepiandrosterone regulates astroglia reaction to denervation of olfactory glomeruliGLIA, Issue 3 2004Zsófia Hoyk Abstract Effects of dehydroepiandrosterone (DHEA) on glial reactions of the peripherally denervated olfactory bulb were studied in adult male rats. Denervation was achieved by destroying the olfactory mucosa with ZnSO4 (0.17 M) irrigation of the nasal cavities. In one series of experiments, chronic DHEA treatment was applied (daily injections for 7 days, i.p., 10 mg/kg b.w. and 25 mg/kg b.w.); in the other series of experiments, animals received a single injection of DHEA (i.p., 10 mg/kg b.w., 25 mg/kg b.w. and 50 mg/kg b.w.) 2 h following ZnSO4 treatment. To determine whether DHEA conversion to estradiol was involved in the mechanism of DHEA action on glia, a third series of experiments was carried out in which the aromatase inhibitor fadrozole (4.16 mg/ml) was administered using subcutaneously implanted osmotic minipumps. Rats were killed on day 7 after chemical denervation, and the reaction of glial cells was monitored within the olfactory bulb, using GFAP and vimentin immunohistochemistry. Qualitative changes in GFAP expression were analyzed by Western blot. Chronic DHEA treatment with both doses (10 mg/kg b.w. and 25 mg/kg b.w.) and acute DHEA treatment with the highest dose applied (50 mg/kg b.w.), inhibited the increase in GFAP expression induced by the denervation of the olfactory bulb. Furthermore, GFAP and vimentin immunostaining in the glomerular layer of the olfactory bulb were diminished in the denervated and DHEA treated groups. However, when DHEA treatment was combined with fadrozole administration, such a decrease in GFAP expression could not be detected in the chemically denervated olfactory bulb. These findings indicate that DHEA, depending on the dose applied and the mode of administration, attenuates glial reaction to denervation and may regulate glial plasticity in the olfactory glomeruli. These effects are likely to be mediated at least in part by the conversion of DHEA to estradiol. © 2004 Wiley-Liss, Inc. [source] Inactivity-induced modulation of Hsp20 and Hsp25 content in rat hindlimb musclesMUSCLE AND NERVE, Issue 1 2004Kimberly A. Huey PhD Abstract Denervation decreases small heat shock protein (HSP) content in the rat soleus muscle; however, it is unknown whether this change is due to inactivity or absence of a nerve,muscle connection. Spinal cord isolation (SI) is a model of inactivity with an intact neuromuscular connection. After 7 days of SI, Hsp20 and Hsp25 levels in the soleus, plantaris, and adductor longus muscles were lower than in control rats, whereas Hsp20 was unchanged and Hsp25 increased in the tibialis anterior. The results for the soleus indicate that these small HSPs respond to inactivity and that this response is not influenced by neural activity,independent factors. Furthermore, the data indicate that these HSPs are impacted to a greater degree in muscles that are predominantly slow or have an antigravity function than in flexor muscles. Understanding the regulation of these HSPs during chronic reductions in neuromuscular activity may have valuable applications for conditions such as spinal cord injury. Muscle Nerve 30: 95,101, 2004 [source] The Surgical Anatomy of Lumbar Medial Branch Neurotomy (Facet Denervation)PAIN MEDICINE, Issue 3 2004Peter Lau FRACR ABSTRACT Objective., To demonstrate the validity of placing electrodes parallel to the target nerve in lumbar radiofrequency neurotomy. DESIGN., Previous data on the anatomy of the lumbar dorsal rami were reviewed and a demonstration cadaver was prepared. Under direct vision, electrodes were placed on, and parallel to, the L4 medial branch and the L5 dorsal ramus. Photographs were taken to record the placement, and radiographs were taken to illustrate the orientation and location of the electrode in relation to bony landmarks. Results., In order to lie in contact with, and parallel to, the target nerve, electrodes need to be inserted obliquely from below, so that their active tip crosses the neck of the superior articular process. At typical lumbar levels, the tip should lie opposite the middle two quarters of the superior articular process. At the L5 level, it should lie opposite the middle and posterior thirds of the S1 superior articular process. Conclusion., If electrodes are placed parallel to the target nerve, the lesions made can be expected to encompass the target nerves. If electrodes are placed perpendicular to the nerve, the nerve may escape coagulation, or be only partially coagulated. Placing the electrode parallel to the nerve has a demonstrated anatomical basis, and has been vindicated clinically. Other techniques lack such a basis, and have not been vindicated clinically. Suboptimal techniques may underlie suboptimal outcomes from lumbar medial branch neurotomy. [source] Denervation of Carotid Baro- and Chemoreceptors in HumansTHE JOURNAL OF PHYSIOLOGY, Issue 1 2003Henri J. L. M. Timmers Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia. [source] Muscle Fiber Regeneration in Human Permanent Lower Motoneuron Denervation: Relevance to Safety and Effectiveness of FES-Training, Which Induces Muscle Recovery in SCI SubjectsARTIFICIAL ORGANS, Issue 3 2005Ugo Carraro Abstract:, Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1- to 37-years postspinal cord injury (SCI). After 2- to 10-years FES-training the muscle cryosections present mainly large round myofibers. In the FES-trained muscles the regenerative events are present, but at a lower rate than long-term denervated muscles (myofiber per mm2 of cryosection area: 0.8 ± 1.3 in FES vs. 2.3 ± 2.3 in DDM, mean ± SD, P = 0.011). In our opinion this is a sound additional evidence of effectiveness of the Kern's electrical stimulation protocol for FES of DDM. In any case, the overall results demonstrate that the FES-training is safe: at least it does not induce more myofiber damage/regeneration than denervation per se. [source] Hepatic denervation impairs the assembly and secretion of VLDL-TAGCELL BIOCHEMISTRY AND FUNCTION, Issue 5 2008Fábio Luís Tavares Abstract VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3,±,10.1 vs. 67.1,±,4.9,mg,dL,1) and VLDL-cholesterol (61.6,±,5.6 vs. 29.4,±,3.3,mg,dL,1), but HDL-cholesterol was unchanged (45.5,±,6.1 vs. 36.9,±,3.9,mg,dL,1). Secretion of VLDL-TAG (47.5,±,23.8 vs. 148.5,±,27.4,mg,dL,h,1) and mRNA expression of CPT I and apoB were reduced (p,<,0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls. Copyright © 2008 John Wiley & Sons, Ltd. [source] Influence of sympathetic and AT1 -receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive ratsACTA PHYSIOLOGICA, Issue 3 2009M. H. Abdulla Abstract Aim:, This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR). Methods:, Forty-eight SHR were subjected to 7 days of losartan (10 mg kg,1 day,1 p.o.), carvedilol (5 mg kg,1 day,1 p.o.) or losartan + carvedilol (10 mg kg,1 day,1 + 5 mg kg,1 day,1 p.o.). On day 8, the rats were anaesthetized and renal vasoconstrictor experiments performed. One group of rats underwent acute unilateral renal denervation. Results:, There were significant (P < 0.05) reductions in the renal vasoconstrictor responses to noradrenaline, phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments compared with that in untreated rats (all P < 0.05). However, in renally denervated SHR treated with carvedilol, the vasoconstrictor responses to all the vasoactive agents were enhanced compared with those in SHR with intact renal nerves treated with carvedilol. Intact SHR given both losartan and carvedilol showed greater renal vasoconstrictor responses to the vasoactive agents than when given either losartan or carvedilol alone (all P < 0.05). Conclusion:, Carvedilol reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in the presence of the renal nerves, but, following the removal of renal sympathetic activity, carvedilol enhanced the sensitivity of both renal ,1 -adrenoceptors and AT1 receptors to the vasoactive agents. Co-treatment with losartan and carvedilol reduced the renal vasoconstrictor responses to exogenously administered vasoactive agents but to a lesser extent than losartan or carvedilol alone. The results obtained demonstrate an interaction between Ang II receptors and adrenergic neurotransmission in the SHR. [source] Blood volume, blood pressure and total body sodium: internal signalling and output controlACTA PHYSIOLOGICA, Issue 1 2009P. Bie Abstract Total body sodium and arterial blood pressure (ABP) are mutually dependent variables regulated by complex control systems. This review addresses the role of ABP in the normal control of sodium excretion (NaEx), and the physiological control of renin secretion. NaEx is a pivotal determinant of ABP, and under experimental conditions, ABP is a powerful, independent controller of NaEx. Blood volume is a function of dietary salt intake; however, ABP is not, at least not in steady states. A transient increase in ABP after a step-up in sodium intake could provide a causal relationship between ABP and the regulation of NaEx via a hypothetical integrative control system. However, recent data show that subtle sodium loading (simulating salty meals) causes robust natriuresis without changes in ABP. Changes in ABP are not necessary for natriuresis. Normal sodium excretion is not regulated by pressure. Plasma renin is log-linearly related to salt intake, and normally, decreases in renin secretion are a precondition of natriuresis after increases in total body sodium. Renin secretion is controlled by renal ABP, renal nerve activity and the tubular chloride concentrations at the macula densa (MD). Renal nerve activity is related to blood volume, also at constant ABP, and elevates renin secretion by means of ,1 -adrenoceptors. Recent results indicate that renal denervation reduces ABP and renin activity, and that sodium loading may decrease renin without changes in ABP, glomerular filtration rate or ,1 -mediated nerve activity. The latter indicates an essential role of the MD mechanism and/or a fourth mediator of the physiological control of renin secretion. [source] Time course of changes in angiogenesis-related factors in denervated muscleACTA PHYSIOLOGICA, Issue 4 2006A. Wagatsuma Abstract Aim:, Denervation leads to capillary regression in skeletal muscle. To gain insight into the regulation of this process, we investigated the time course of changes in capillary supply and gene expression of angiogenesis-related factors during muscle denervation. Method:, Female mice underwent surgery to transect the sciatic nerve, and then the gastrocnemius muscles were isolated at 12 h, 1, 3, 5, 10, 20, or 30 days after surgery. The capillary supply was assessed by immunohistochemistry using anti-PECAM-1/CD31 antibody. The mRNA levels for angiogenesis-related factors were analysed using a real-time polymerase chain reaction. Results:, We found that the capillary-to-fibre ratio began to decrease 10 days after muscle denervation and decreased by 52% after 30 days. The levels of mRNA for vascular endothelial growth factor (VEGF), its receptors [fms-like tyrosine kinase (Flt-1) and a kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1)], angiopoietin-1 and angiopoietin-2 of denervated muscle were immediately down-regulated after 12 h and remained lower than control muscle until 30 days after muscle denervation. The levels of mRNA for the VEGF receptor, neuropilin-1, angiopoietin receptor and Tie-2 decreased within 12,24 h, but returned to near those of control muscle after 10,20 days, and again decreased after 30 days. Conclusions:, These findings suggest that denervation-induced capillary regression may be associated with down-regulation of VEGF and angiopoietin signalling. [source] Mechanisms of genioglossus responses to inspiratory resistive load in rabbitsACTA PHYSIOLOGICA, Issue 3 2002N. P. ALEKSANDROVA ABSTRACT The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were `bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 ± 14.7% of control) and its inspiratory duration (to 113 ± 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 ± 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (,13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of `pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory load compensations. [source] Factors regulating renal angiotensin-converting enzyme activity in the ratACTA PHYSIOLOGICA, Issue 1 2000Changes in angiotensin-converting enzyme (ACE) activity appear to be important in mediating the natriuresis which ensues after administration of an oral or gastric sodium load. In this study, we sought to determine the time course of the changes in ACE activity in the kidney which occur after sodium ingestion. In addition, we sought to investigate mechanisms which might underlie these changes. Angiotensin-converting enzyme activity was measured by generation of histidyl-leucine in homogenates of kidneys harvested at varying time-points after gastric sodium administration. The effects of intravenous sodium loading, solution osmolality and of changes in renal nerve activity were also investigated. Intragastric instillation of both the sodium-containing solution and its iso-osmotic urea control solution resulted in significant increases in renal ACE activity (NaCl: P < 0.0005; Urea: P < 0.01). The increase in renal ACE activity after gastric sodium loading was more prolonged than after the urea control (P < 0.025, NaCl vs. urea at 90 min). This prolonged increase in renal ACE activity appeared to reflect a response to absorbed sodium as intravenous sodium administration caused a significant increase in renal ACE activity at 90 min (P < 0.0005). In contrast to these stimuli which increased renal ACE activity, renal denervation caused a significant decrease in ACE activity in the kidney (P < 0.05). We conclude that gastric sodium loading increases renal ACE activity. This effect appears to be due initially to a response to an increase in gastric lumenal osmolality and later to absorbed sodium. These changes in renal ACE activity are not mediated by a decrease in renal nerve activity. [source] Activity alters muscle reinnervation and terminal sprouting by reducing the number of schwann cell pathways that grow to link synaptic sitesDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2003Flora M. Love Abstract In partially denervated rodent muscle, terminal Schwann cells (TSCs) located at denervated end plates grow processes, some of which contact neighboring innervated end plates. Those processes that contact neighboring synapses (termed "bridges") appear to initiate nerve terminal sprouting and to guide the growth of the sprouts so that they reach and reinnervate denervated end plates. Studies conducted prior to knowledge of this potential involvement of Schwann cells showed that direct muscle stimulation inhibits terminal sprouting following partial denervation (Brown and Holland, 1979). We have investigated the possibility this inhibition results from an alteration in the growth of TSC processes. We find that stimulation of partially denervated rat soleus muscle does not alter the length or number of TSC processes but does reduce the number of TSC bridges. Stimulation also reduces the number of TSC bridges that form between end plates during reinnervation of a completely denervated muscle. The nerve processes ("escaped fibers") that normally grow onto TSC processes during reinnervation are also reduced in length. Therefore, stimulation alters at least two responses to denervation in muscles: (1) the ability of TSC processes to form or maintain bridges with innervated synaptic sites, and (2) the growth of axons along processes extended by TSCs. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 566,576, 2003 [source] Effect of chronic denervation and denervation-reinnervation on cytoplasmic creatine kinase transcript accumulationDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Charles H. Washabaugh Abstract The extensor digitorum longus (EDL) and soleus muscles of adult mice were chronically denervated or denervated and allowed to reinnervate. Muscles were evaluated 1, 5, 14, 21, and 52 days after sciaticectomy. In terms of weight loss, myofiber atrophy, degeneration, and fibrosis, the soleus muscle was more affected than the EDL by chronic denervation. Fifty-two days after chronic denervation, the number of molecules of MCK/ng total RNA in both muscles (determined with competitive PCR) decreased, with the soleus muscle being more affected. At that stage, BCK mRNA levels in the denervated soleus were unchanged, but they were increased (>50%) in the EDL. Reinnervation restored MCK transcript accumulation in the EDL, whereas, in the soleus MCK, transcripts exceeded control values by 57%, approaching levels in the reinnervated EDL. Despite restoration of MCK mRNA levels, the number of molecules of BCK mRNA/ng total RNA was four- to fivefold higher in reinnervated versus control muscles, suggesting that the genes encoding the CK mRNAs are not coordinately regulated in adult muscle. The role of denervation induced, fiber type changes in regulating CK mRNA accumulation has been evaluated. Electron microscopic analyses have established that fibrosis is not a factor that determines BCK mRNA levels in the chronically denervated or denervated-reinnervated muscles. CK isozyme analyses support the hypothesis that a greater proportion of BCK mRNA found in 52 day chronically denervated and denervated-reinnervated muscles is produced in myofibers vs. nonmuscle cells than in control muscles. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 194,206, 2001 [source] Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal studyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2007Raffaele Antonelli Incalzi Abstract Background and aim Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up. Methods Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG. Results During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 ± 30.14 min at baseline and 92.10 ± 24.52 min at the end of follow-up) and without AN (135.14 ± 17.09 min and 92.68 ± 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho , 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values. Conclusions Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effects of hind limb denervation on the development of appendicular ossicles in the Dwarf African Clawed Frog, Hymenochirus boettgeri (Anura: Pipidae)ACTA ZOOLOGICA, Issue 4 2009Hyoung Tae Kim Abstract Sesamoids and other appendicular ossicles are common in other classes of vertebrates but comparatively rare in amphibians. The pipid frog Hymenochirus boettgeri (Boulenger, G. A. 1899. On Hymenochirus, a new type of aglossal batrachians. , Annals of the Magazine of Natural History Series 7: 122,125) is unusual among anurans in having seven (or more) appendicular ossicles in each hind limb. Sesamoids are often associated with muscles and tendons, and their development is usually regarded as mediated by or correlated with function. This study investigated the effects of paralysis (loss of function) on development of ossicles in the hind limb of Hymenochirus. Complete denervation of the right sciatic nerve was performed at developmental stages 63 and 66, and the animals maintained for a further 6,7 or 12,13 weeks. Specimens were cleared and double stained for cartilage and bone. There were no gross morphological differences between control and sham operated groups. The lunulae were not affected by paralysis, whereas the fabella arose later and/or regressed in some specimens. The distal os sesamoides tarsalia (OST) was shorter in paralysed individuals, and both the distal OST and cartilagines plantares showed delayed maturation. Denervation of the hind limb thus affected the timing of appearance, maintenance and rate of maturation of some sesamoid bones in Hymenochirus, but had no effect on others. [source] Transection of the sciatic nerve and reinnervation in adult rats: muscle and endplate morphologyEQUINE VETERINARY JOURNAL, Issue S33 2001J. IJKEMA-PAASSEN Summary The functional recovery after peripheral nerve lesions is generally poor. We studied whether changes in muscles after reinnervation might explain such disappointing results. The functional recovery after peripheral nerve lesions is generally poor. Changes in muscle morphology and neuromuscular innervation might partly explain this lack of compensation. In order to test this hypothesis, we studied muscular differentiation in the soleus, gastrocnemius and tibialis anterior muscles at 7, 15 and 21 weeks after a sciatic nerve lesion in adult rats. In the gastrocnemius and tibialis muscles the percentages of type II muscles fibres were decreased at 7 and 15 weeks but at 21 weeks they again approached normal values. The soleus muscle, however, was permanently decreased in size and this muscle, in contrast to the normal soleus muscle, contained mainly type II fibres. The morphology of the endplates showed distinct stages of degeneration and reinnervation. Two weeks after denervation, in rats in which reinnervation was prevented, all 3 muscles contained considerable numbers of morphologically abnormal endplates and, after 7 weeks, no endplates were detected. During reinnervation, endplates showing signs of acetylcholinesterase activity were observed in all 3 muscles from 7 weeks. At later ages a shift towards morphologically normal endplates occurred, but complete recovery was not observed. Endplates in all 3 muscles were polyneurally innervated at 7 weeks. Although these percentages decreased over age, polyneural innervation was still present at 21 weeks. We conclude that the changes in the distribution of fibre types, abnormal endplate morphology and polyneural innervation may in part explain the poor functional recovery after peripheral nerve lesions. [source] A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task ForceEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2006A. Albanese chairman To review the literature on primary dystonia and dystonia plus and to provide evidence-based recommendations. Primary dystonia and dystonia plus are chronic and often disabling conditions with a widespread spectrum mainly in young people. Computerized MEDLINE and EMBASE literature reviews (1966,1967 February 2005) were conducted. The Cochrane Library was searched for relevant citations. Diagnosis and classification of dystonia are highly relevant for providing appropriate management and prognostic information, and genetic counselling. Expert observation is suggested. DYT-1 gene testing in conjunction with genetic counselling is recommended for patients with primary dystonia with onset before age 30 years and in those with an affected relative with early onset. Positive genetic testing for dystonia (e.g. DYT-1) is not sufficient to make diagnosis of dystonia. Individuals with myoclonus should be tested for the epsilon-sarcoglycan gene (DYT-11). A levodopa trial is warranted in every patient with early onset dystonia without an alternative diagnosis. Brain imaging is not routinely required when there is a confident diagnosis of primary dystonia in adult patients, whereas it is necessary in the paediatric population. Botulinum toxin (BoNT) type A (or type B if there is resistance to type A) can be regarded as first line treatment for primary cranial (excluding oromandibular) or cervical dystonia and can be effective in writing dystonia. Actual evidence is lacking on direct comparison of the clinical efficacy and safety of BoNT-A vs. BoNT-B. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for generalized or cervical dystonia, after medication or BoNT have failed to provide adequate improvement. Selective peripheral denervation is a safe procedure that is indicated exclusively in cervical dystonia. Intrathecal baclofen can be indicated in patients where secondary dystonia is combined with spasticity. The absolute and comparative efficacy and tolerability of drugs in dystonia, including anticholinergic and antidopaminergic drugs, is poorly documented and no evidence-based recommendations can be made to guide prescribing. [source] Post-lesion transcommissural growth of olivary climbing fibres creates functional synaptic microzonesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Izumi Sugihara Abstract In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, postlesion plasticity may generate alternate paths, providing models to investigate reinnervating axon,target interactions. After unilateral transection of the neonatal rat olivocerebellar path, axons from the ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF)-like arbors on Purkinje cells (PCs). However, the synaptic function and extent of PC reinnervation remain unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and electrophysiological properties of reinnervating olivocerebellar axons were studied, using axonal reconstruction and patch-clamp PC recording of CF-induced synaptic currents. Reinnervated PCs displayed normal CF currents, and the frequency of PC reinnervation decreased with increasing laterality. Reinnervating CF arbors were predominantly normal but 6% branched within the molecular layer forming smaller secondary arbors. CFs arose from transcommissural olivary axons, which branched extensively near their target PCs to produce on average 36 CFs, which is six times more than normal. Axons terminating in the hemisphere developed more CFs than those terminating in the vermis. However, the precise parasagittal microzone organization was preserved. Transcommissural axons also branched, although to a lesser extent, to the deep cerebellar nuclei and terminated in a distribution indicative of the olivo-cortico-nuclear circuit. These results show that reinnervating olivocerebellar axons are highly plastic in the cerebellum, compensating anatomically and functionally for early postnatal denervation, and that this reparation obeys precise topographic constraints although axonal plasticity is modified by target (PC or deep nuclear neurons) interactions. [source] Facial nerve injury-induced disinhibition in the primary motor cortices of both hemispheresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000Tamás Farkas Abstract Unilateral facial nerve transection induces plastic reorganization of the somatotopic order in the primary motor cortex area (MI). This process is biphasic and starts with a transient disinhibition of connections between cortical areas in both hemispheres. Little is known about the underlying mechanisms. Here, cortical excitability has been studied by paired pulse electrical stimulation, applied either within the MI or peripherally to the trigeminal nerve, while the responses were recorded bilaterally in the MI. The ratios between the amplitudes of the second and first evoked potentials (EPs or fEPSPs) were taken as measures of the inhibitory capacity in the MI ipsilateral or contralateral to the nerve injury. A skin wound or unilateral facial nerve exposure immediately caused a transient facilitation, which was followed by a reset to some level of inhibition in the MI on both sides. After facial nerve transection, the first relatively mild reduction of inhibition started shortly (within 10 min) after denervation. This was followed by a second step, involving a stronger decrease in inhibition, 40,45 min later. Previous publications have proved that sensory nerve injury (deafferentation) induces disinhibition in corresponding areas of the sensory cortex. It is now demonstrated that sham operation and, to an even greater extent, unilateral transection of the purely motoric facial nerve (deefferentation), each induce extended disinhibition in the MIs on both sides. [source] Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000Pascal Barnéoud Abstract We have examined the behavioural consequences of a partial unilateral dopaminergic denervation of the rat striatum. This partial lesion was obtained by an intrastriatal 6-hydroxy-dopamine injection (6-OHDA, 20 or 10 ,g divided between two injection sites) and was compared with a unilateral complete lesion resulting from an injection of 6-OHDA (2 × 6 ,g) into the medial forebrain bundle. Quantification of striatal dopamine (DA) and its metabolites, and the immunohistochemical evaluation of the nigrostriatal DA system confirmed the complete and partial lesions. Animals with complete striatal denervation displayed both apomorphine- and amphetamine-induced rotations whereas the partial denervation elicited amphetamine-induced rotations only. However, the rates of amphetamine-induced rotation were not correlated with the size of the lesion. In contrast, the paw-reaching impairments were significantly correlated with the striatal dopaminergic depletion. When evaluated in the staircase test, animals with partial denervation were impaired exclusively for the paw contralateral to the side of the lesion. This motor deficit (50,75%) included all components of the skilled paw use (i.e. attempt, motor coordination and success) and was observed at least 12 weeks after the lesion. However, these animals were able to perform normal stepping adjustments with the impaired paw, indicating that the partial lesion induced a coordination deficit of the paw rather than a deficit of movement initiation. After a complete lesion, stepping adjustments of the contralateral paw were dramatically impaired (by 80%), an akinesia which almost certainly accounted for the great deficit in skilled paw use. The paw-reaching impairments resulting from the partial striatal denervation are proposed as a model of the early symptoms of Parkinson's disease and may be useful for the development of restorative therapies. [source] Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000Jean Michel Brezun Abstract The long-term effects of hippocampal serotonergic denervation and reinnervation by foetal raphe tissue were examined in the dentate gyrus where neurons are continously born in the adult. Complete lesion of serotonin neurons following injections of 5,7-dihydroxytryptamine in the dorsal and medial raphe nuclei produced long-term decreases in the number of newly generated granule cells identified with 5-Bromo-2,-deoxyuridine (BrdU) and the polysialylated form of neural cell adhesion molecule (PSA-NCAM) immunostaining, as observed in 2-month-survival rats. The raphe grafts, but not the control grafts of embryonic spinal tissue, reversed the postlesion-induced decreases in the density of BrdU- and PSA-NCAM-labelled cells detected in the granule layer. Inhibition of serotonin synthesis in animals with raphe grafts reversed back to lesion-induced changes in granule cell proliferation. Furthermore, extensive serotonergic reinnervation of the dentate gyrus in the area proximal to the raphe graft could be associated with supranormal density of BrdU-labelled cells. These results indicate that serotonin may be considered a positive regulatory factor of adult granule cell proliferation. Finally, the lack of effect of embryonic nonserotonergic tissue grafted to serotonin-deprived rats suggests that neurotrophic factors may not be involved in the effects of serotonin on adult neurogenesis. [source] Sympathectomy suppresses tumor growth and alters gene-expression profiles in rat tongue cancerEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2009Bina Raju Sympathetic nerves are known to affect carcinogenesis. Recently we found that sympathetic denervation decreases the size of rat tongue tumors. To identify genes involved in rat tongue carcinogenesis and to study the effect of sympathetic nerves on these genes, we compared gene-expression profiles in normal rat tongue (control) and in tumor-induced tongues with (SCGx) and without (Sham) bilateral sympathectomy. Significance analysis of microarrays revealed 280 genes (168 up-regulated, 112 down-regulated) that showed at least a twofold differential expression between Sham and SCGx tumors (false discovery rate < 5%). These included genes associated with cell adhesion, signaling, structure, proliferation, metabolism, angiogenesis, development, and immunity. Hierarchical clustering demonstrated that controls and sympathectomized tumors grouped together, while Sham tumors grouped separately. We identified 34 genes, known to be involved in carcinogenesis, that were not differentially expressed between sympathectomized tumors and control tongues, but which showed a significant change in expression in Sham tumors. Microarray results of 12 of these genes were confirmed by quantitative reverse transcription,polymerase chain reaction. In conclusion, sympathectomy significantly altered the gene-expression profile and inhibited tumor growth. The expression of several cancer genes were increased more than threefold in Sham tumors, but unaltered in the sympathectomized tumors when compared with controls, indicating that these genes may be of significance in rat tongue carcinogenesis. [source] Region-specific changes in sympathetic nerve activity in angiotensin II,salt hypertension in the ratEXPERIMENTAL PHYSIOLOGY, Issue 1 2010John W. Osborn It is now well accepted that many forms of experimental hypertension and human essential hypertension are caused by increased activity of the sympathetic nervous system. However, the role of region-specific changes in sympathetic nerve activity (SNA) in the pathogenesis of hypertension has been difficult to determine because methods for chronic measurement of SNA in conscious animals have not been available. We have recently combined indirect, and continuous and chronic direct, assessment of region-specific SNA to characterize hypertension produced by administration of angiotensin II (Ang II) to rats consuming a high-salt diet (Ang II,salt hypertension). Angiotensin II increases whole-body noradrenaline (NA) spillover and depressor responses to ganglionic blockade in rats consuming a high-salt diet, but not in rats on a normal-salt diet. Despite this evidence for increased ,whole-body SNA' in Ang II,salt hypertensive rats, renal SNA is decreased in this model and renal denervation does not attenuate the steady-state level of arterial pressure. In addition, neither lumbar SNA, which largely targets skeletal muscle, nor hindlimb NA spillover is changed from control levels in Ang II,salt hypertensive rats. However, surgical denervation of the splanchnic vascular bed attenuates/abolishes the increase in arterial pressure and total peripheral resistance, as well as the decrease in vascular capacitance, observed in Ang II,salt hypertensive rats. We hypothesize that the ,sympathetic signature' of Ang II,salt hypertension is characterized by increased splanchnic SNA, no change in skeletal muscle SNA and decreased renal SNA, and this sympathetic signature creates unique haemodynamic changes capable of producing sustained hypertension. [source] Angiotensin II-based hypertension and the sympathetic nervous system: the role of dose and increased dietary salt in rabbitsEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Fiona D. McBryde There is accumulating evidence that angiotensin II may exert its hypertensive effect through increasing sympathetic drive. However, this action may be dependent on the dose of angiotensin II as well as salt intake. We determined the effect of different doses of angiotensin II and different levels of salt intake on neurogenic pressor activity. We also examined the effect of renal denervation. New Zealand White rabbits were instrumented to continuously measure arterial pressure. The depressor response to the ganglionic blocker pentolinium tartrate (5 mg kg,1) was used to assess pressor sympathetic drive on days 0, 7 and 21 of a 20 or 50 ng kg,1 min,1 continuous i.v. angiotensin II infusion. A 50 ng kg,1 min,1 infusion caused an immediate increase in pressure (23 ± 5 mmHg), whereas a 20 ng kg,1 min,1 infusion caused a slow increase in pressure, peaking by day 12 (17 ± 4 mmHg). The ganglionic blockade profiles indicated sympathoinhibition in the 50 ng kg,1 min,1 group by day 7 and sympathoinhibition in the 20 ng kg,1 min,1 group at day 21, corresponding to the development of hypertension. Animals receiving increased dietary salt (0.9% NaCl in drinking water), however, showed a similar slow increase in pressure with 20 ng kg,1 min,1 angiotensin II (16 ± 5 mmHg) but no sympathoinhibition at day 21. Bilateral renal denervation delayed the onset but not the extent of hypertension in this group. We conclude that different doses of angiotensin II produce distinct profiles of hypertension and associated changes in pressor sympathetic drive and that increased dietary salt intake disrupts the normal sympathoinhibitory response to angiotensin II-based hypertension. [source] Regional sympathetic denervation affects the relation between canine local myocardial blood flow and oxygen consumptionEXPERIMENTAL PHYSIOLOGY, Issue 3 2007David J. C. Alders Myocardial blood flow and oxygen consumption are heterogeneously distributed. Perfusion and myocardial oxygen consumption are closely correlated in the normal heart. It is unknown how this metabolism,perfusion relation is influenced by sympathetic denervation. We investigated this question in seven chloralose-anaesthetized dogs, 3,4 weeks after regional sympathetic denervation of the left circumflex coronary artery area of supply of the left ventricle. Measurements were made of local myocardial blood flow (MBF, in ml min,1 (g dry wt),1), measured with microspheres, and myocardial oxygen consumption (, in ,mol min,1 (g dry wt),1) in the same location, calculated from the 13C spectrum of tissue extracts after intracoronary infusion of 3,13C-lactate. Since both innervated and denervated regions are subject to the same arterial pressure, lower blood flow indicates higher resistance. Mean MBF was 5.56 ml min,1 (g dry wt),1 (heterogeneity of 3.47 ml min,1 (g dry wt),1) innervated, 7.48 ml min,1 (g dry wt),1 (heterogeneity of 3.62 ml min,1 (g dry wt),1) denervated (n.s.). Significant linear relations were found between MBF and of individual samples within the innervated and denervated regions. The slopes of these relations were not significantly different, but the adjusted mean was significantly higher in the denervated regions (+1.92 ml min,1 (g dry wt),1, an increase of 38% of the mean MBF at the pooled mean , P= 0.028, ANCOVA). The ratio (in ml ,mol,1) was significantly higher, being 0.296 ± 0.167 ml ,mol,1 in the denervated region compared with the innervated region, 0.216 ± 0.126 ml ,mol,1, P= 0.0182, Mann,Whitney U test. These results indicate that sympathetic tone under chloralose anaesthesia imposes a moderate vasoconstrictive effect in the myocardium that is not detected by comparison of the mean blood flow or resistance. [source] The otic ganglion in rats and its parotid connection: cholinergic pathways, reflex secretion and a secretory role for the facial nerveEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Nina Khosravani Otic ganglionectomy in rats was found to have affected the parotid gland more profoundly than section of the auriculotemporal nerve as assesssed by reduction in gland weight (by 33 versus 20%) and total acetylcholine synthesizing capacity (by 88 versus 76%) 1 week postoperatively and, when assessed on the day of surgery under adrenoceptor blockade, by reflex secretion (by 99 versus 88%). The facial nerve contributed to the acetylcholine synthesizing capacity of the gland. Section of the nerve only, at the level of the stylomastoid foramen, reduced the acetylcholine synthesis by 15% and, combined with otic ganglionectomy, by 98% or, combined with section of the auriculotemporal nerve, by 82%. The facial nerve was secretory to the gland, and the response was of a cholinergic nature. The nerve conveyed reflex secretion of saliva and caused secretion of saliva upon stimulation. Most of the facial secretory nerve fibres originated from the otic ganglion, since after otic ganglionectomy (and allowing for nerve degeneration) the secretory response to facial nerve stimulation was markedly reduced (from 23 to 4 ,l (5 min),1). The persisting secetory response after otic ganglionectomy, exaggerated due to sensitization, and the residual acetylcholine synthesizing capacity (mainly depending on the facial nerve) showed that a minor proportion of pre- and postganglionic nerve fibres relay outside the otic ganglion. The great auricular nerve, which like the facial nerve penetrates the gland, caused no secretion of saliva upon stimulation. Avulsion of the auriculotemporal nerve was more effective than otic ganglionectomy in reducing the acetylcholine synthesizing capacity (by 94 versus 88%) and as effective as otic ganglionectomy in abolishing reflex secretion (by 99%). When aiming at parasympathetic denervation, avulsion may be the preferable choice, since it is technically easier to perform than otic ganglionectomy. [source] Capillary supply and gene expression of angiogenesis-related factors in murine skeletal muscle following denervationEXPERIMENTAL PHYSIOLOGY, Issue 3 2005A. Wagatsuma Capillary supply of skeletal muscle decreases during denervation. To gain insight into the regulation of this process, we investigated capillary supply and gene expression of angiogenesis-related factors in mouse gastrocnemius muscle following denervation for 4 months. Frozen transverse sections were stained for alkaline phosphatase to detect endogenous enzyme in the capillary endothelium. The mRNA for angiogenesis-related factors, including hypoxia inducible factor-1, (HIF-1,), vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1), fms-like tyrosine kinase (Flt-1), angiopoietin-1 and tyrosine kinase with Ig and epidermal growth factor(EGF) homology domain 2 (Tie-2), was analysed using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The fibre cross-sectional area after denervation was about 20% of the control value, and the capillary to fibre ratio was significantly lower in denervated than in control muscles. The number of capillaries around each fibre also decreased to about 40% of the control value. These observations suggest that muscle capillarity decreases in response to chronic denervation. RT-PCR analysis showed that the expression of VEGF mRNA was lower in denervated than in control muscles, while the expression of HIF-1, mRNA remained unchanged. The expression levels of the KDR/Flk-1 and Flt-1 genes were decreased in the denervated muscle. The expression levels of angiopoietin-1 but not Tie-2 genes were decreased in the denervated muscle. These findings indicate that reduction in the expression of mRNAs in the VEGF/KDR/Flk-1 and Flt-1 as well as angiopoietin-1/Tie-2 signal pathways might be one of the reasons for the capillary regression during chronic denervation. [source] Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodellingFEBS JOURNAL, Issue 3 2009Lydie Laure In an attempt to identify potential therapeutic targets for the correction of muscle wasting, the gene expression of several pivotal proteins involved in protein metabolism was investigated in experimental atrophy induced by transient or definitive denervation, as well as in four animal models of muscular dystrophies (deficient for calpain 3, dysferlin, ,-sarcoglycan and dystrophin, respectively). The results showed that: (a) the components of the ubiquitin,proteasome pathway are upregulated during the very early phases of atrophy but do not greatly increase in the muscular dystrophy models; (b) forkhead box protein O1 mRNA expression is augmented in the muscles of a limb girdle muscular dystrophy 2A murine model; and (c) the expression of cardiac ankyrin repeat protein (CARP), a regulator of transcription factors, appears to be persistently upregulated in every condition, suggesting that CARP could be a hub protein participating in common pathological molecular pathway(s). Interestingly, the mRNA level of a cell cycle inhibitor known to be upregulated by CARP in other tissues, p21WAF1/CIP1, is consistently increased whenever CARP is upregulated. CARP overexpression in muscle fibres fails to affect their calibre, indicating that CARP per se cannot initiate atrophy. However, a switch towards fast-twitch fibres is observed, suggesting that CARP plays a role in skeletal muscle plasticity. The observation that p21WAF1/CIP1 is upregulated, put in perspective with the effects of CARP on the fibre type, fits well with the idea that the mechanisms at stake might be required to oppose muscle remodelling in skeletal muscle. [source] Dehydroepiandrosterone regulates astroglia reaction to denervation of olfactory glomeruliGLIA, Issue 3 2004Zsófia Hoyk Abstract Effects of dehydroepiandrosterone (DHEA) on glial reactions of the peripherally denervated olfactory bulb were studied in adult male rats. Denervation was achieved by destroying the olfactory mucosa with ZnSO4 (0.17 M) irrigation of the nasal cavities. In one series of experiments, chronic DHEA treatment was applied (daily injections for 7 days, i.p., 10 mg/kg b.w. and 25 mg/kg b.w.); in the other series of experiments, animals received a single injection of DHEA (i.p., 10 mg/kg b.w., 25 mg/kg b.w. and 50 mg/kg b.w.) 2 h following ZnSO4 treatment. To determine whether DHEA conversion to estradiol was involved in the mechanism of DHEA action on glia, a third series of experiments was carried out in which the aromatase inhibitor fadrozole (4.16 mg/ml) was administered using subcutaneously implanted osmotic minipumps. Rats were killed on day 7 after chemical denervation, and the reaction of glial cells was monitored within the olfactory bulb, using GFAP and vimentin immunohistochemistry. Qualitative changes in GFAP expression were analyzed by Western blot. Chronic DHEA treatment with both doses (10 mg/kg b.w. and 25 mg/kg b.w.) and acute DHEA treatment with the highest dose applied (50 mg/kg b.w.), inhibited the increase in GFAP expression induced by the denervation of the olfactory bulb. Furthermore, GFAP and vimentin immunostaining in the glomerular layer of the olfactory bulb were diminished in the denervated and DHEA treated groups. However, when DHEA treatment was combined with fadrozole administration, such a decrease in GFAP expression could not be detected in the chemically denervated olfactory bulb. These findings indicate that DHEA, depending on the dose applied and the mode of administration, attenuates glial reaction to denervation and may regulate glial plasticity in the olfactory glomeruli. These effects are likely to be mediated at least in part by the conversion of DHEA to estradiol. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||