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Reinnervation
Kinds of Reinnervation Selected AbstractsEffect 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] Long-term morphometric and immunohistochemical findings in human free microvascular muscle flaps,MICROSURGERY, Issue 1 2004M. Susanna C. Kauhanen M.D., Ph.D. Reinnervation, muscle regeneration, density of microvessels, and muscle-type specific atrophy were studied 3,4 years after surgery in surgically nonreinnervated free microvascular muscle flaps to 13 patients transplanted to the upper or lower extremities. Routine histology and immunohistochemistry for PGP 9.5 and S-100 (neuronal markers), Ki-67 (cell proliferation), myosin (muscle fiber types), and CD-31 (endothelium) were carried out, and results were analyzed morphometrically. Three to 4 years after surgery, severe atrophy of predominantly slow-type fibers was seen in 9 cases. In 4 cases, muscle-fiber diameter and fiber-type distribution were close to normal. Long intraoperative muscle ischemia and postoperative immobilization were associated with poor muscle bulk in flaps. The density of microvessels in flaps did not differ from control muscles. PGP 9.5 and S-100 immunopositive nerve fibers were detected in 7 patients. Reinnervation was associated with good muscle bulk. In 4 patients, activation of satellite cells was evident. The results suggest that in some cases, spontaneous reinnervation may occur in free muscle flaps, and that several years after microvascular free flap transfer, the muscle still attempts to regenerate. © 2004 Wiley-Liss, Inc. [source] Morphologic Correlates for Laryngeal Reinnervation,THE LARYNGOSCOPE, Issue 11 2001Richard R. Gacek MD Abstract Objective To describe morphologic correlates for laryngeal reinnervation. Study Design Review of anatomic experiments dealing with laryngeal innervation performed over a 25-year period. Methods Description of results from experimental studies on the cat and human laryngeal muscles and nerve supply. Results Despite separation of abductor and adductor laryngeal motor neurons in the central nervous system, the mixture of abductor and adductor axons in the recurrent laryngeal nerve indicates that selective re-innervation of an individual laryngeal muscle must be accomplished at the neuromuscular junction (NMJ) of the muscle. The optimal time for a reinnervating neural source to re-occupy vacated NMJ is at the time of denervation. If the reinnervation procedure is attempted long (>1 mo) after denervation, extraneous end plates of other neural systems must be eliminated to provide vacant NMJ. The nerve muscle pedicle (NMP) concept is an effective model for reinnervation of a laryngeal muscle provided its activity pattern is similar to that of the denervated muscle and its insertion into vacated NMJ is timely. Conclusion NMP offers a logical method for selective laryngeal muscle reinnervation. Critical to the success of NMP are the physiological input to the NMP and timing of NMP implantation. [source] Laryngeal Reinnervation With the Hypoglossal NerveTHE LARYNGOSCOPE, Issue 6 2001J. J. Manni MD No abstract is available for this article. [source] Differential expression of TrkB isoforms switches climbing fiber-Purkinje cell synaptogenesis to selective synapse eliminationDEVELOPMENTAL NEUROBIOLOGY, Issue 10 2009Rachel M. Sherrard Abstract Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood. We assessed the role of cerebellar neurotrophins by examining tropomycin receptor kinase (Trk) receptor expression in the inferior olive and cerebellum between postnatal days (P)3-7, when CF-PC innervation changes from synapse formation to selective synapse elimination, and in a denervation-reinnervation model when synaptogenesis is delayed. Trks A, B, and C are expressed in olivary neurons; although TrkA was not transported to the cerebellum and TrkC was unchanged during innervation and reinnervation, suggesting that neither receptor is involved in CF-PC synaptogenesis. In contrast, both total and truncated TrkB (TrkB.T) increased in the olive and cerebellum from P4, whereas full-length and activated phosphorylated TrkB (phospho-TrkB) decreased from P4-5. This reveals less TrkB signaling at the onset of CF regression. This expression pattern was reproduced during CF-PC reinnervation: in the denervated hemicerebellum phospho-TrkB decreased as CF terminals degenerated, then increased in parallel with the delayed neosynaptogenesis as new CFs reinnervated the denervated hemicerebellum. In the absence of this signaling, CF reinnervation did not develop. Our data reveal that olivocerebellar TrkB activity parallels CF-PC synaptic formation and stabilization and is required for neosynaptogenesis. Furthermore, TrkB.T expression rises to reduce TrkB signaling and permit synapse elimination. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [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] 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] Developmental neural plasticity and its cognitive benefits: olivocerebellar reinnervation compensates for spatial function in the cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Melina L. Willson Abstract The adult mammalian central nervous system displays limited reinnervation and recovery from trauma. However, during development, post-lesion plasticity may generate alternative paths, thus providing models to investigate reinnervation and repair. After unilateral transection of the neonatal rat olivocerebellar path (pedunculotomy), axons from the remaining inferior olive reinnervate the denervated hemicerebellum. Unfortunately, reinnervation to the cerebellar hemisphere is incomplete; therefore, its capacity to mediate hemispheric function (navigation) is unknown. We studied sensorimotor control and spatial cognition of rats with and without transcommissural reinnervation using simple (bridge and ladder) and complex (wire) locomotion tests and the Morris water maze (hidden, probe and cued paradigms). Although pedunculotomized animals completed locomotory tasks more slowly than controls, all groups performed equally in the cued maze, indicating that lesioned animals could orientate to and reach the platform. In animals pedunculotomized on day 3 (Px3), which develop olivocerebellar reinnervation, final spatial knowledge was as good as controls, although they learned more erratically, failing to retain all information from one day to the next. By contrast, animals pedunculotomized on day 11 (Px11), which do not develop reinnervation, did not learn the task, taking less direct routes and more time to reach the platform than controls. In the probe test, control and Px3, but not Px11, animals swam directly to the remembered location. Furthermore, the amount of transcommissural reinnervation to the denervated hemisphere correlated directly with spatial performance. These results show that transcommissural olivocerebellar reinnervation is associated with spatial learning, i.e. even partial circuit repair confers significant functional benefit. [source] Effect of neurotrophin-3 on reinnervation of the larynx using the phrenic nerve transfer techniqueEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007Paul J. Kingham Abstract Current techniques for reinnervation of the larynx following recurrent laryngeal nerve (RLN) injury are limited by synkinesis, which prevents functional recovery. Treatment with neurotrophins (NT) may enhance nerve regeneration and encourage more accurate reinnervation. This study presents the results of using the phrenic nerve transfer method, combined with NT-3 treatment, to selectively reinnervate the posterior cricoarytenoid (PCA) abductor muscle in a pig nerve injury model. RLN transection altered the phenotype and morphology of laryngeal muscles. In both the PCA and thyroarytenoid (TA) adductor muscle, fast type myosin heavy chain (MyHC) protein was decreased while slow type MyHC was increased. These changes were accompanied with a significant reduction in muscle fibre diameter. Following nerve repair there was a progressive normalization of MyHC phenotype and increased muscle fibre diameter in the PCA but not the TA muscle. This correlated with enhanced abductor function indicating the phrenic nerve accurately reinnervated the PCA muscle. Treatment with NT-3 significantly enhanced phrenic nerve regeneration but led to only a small increase in the number of reinnervated PCA muscle fibres and minimal effect on abductor muscle phenotype and morphology. Therefore, work exploring other growth factors, either alone or in combination with NT-3, is required. [source] Afferent,target interactions during olivocerebellar development: transcommissural reinnervation indicates interdependence of Purkinje cell maturation and climbing fibre synapse eliminationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Ann M. Lohof Abstract We have used a model of postlesional reinnervation to observe the interactions between synaptic partners during neosynaptogenesis to determine how the developmental states of the pre- and postsynaptic cells influence circuit maturation. After unilateral transection of the neonatal rat olivocerebellar pathway (pedunculotomy), axons from the remaining ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF) terminal arbors on Purkinje cells (PCs) at a later stage of development than normal. However, the significance of delayed CF-PC interactions on subsequent circuit maturation remains poorly defined. To examine this question, we recorded CF-induced currents in PCs and analysed PC morphology during the first two postnatal weeks in control animals and following left unilateral inferior cerebellar pedunculotomy on postnatal day (P)3. Our results show that transcommissural olivary axons multiply-reinnervate PCs in the denervated hemisphere over 4 days following pedunculotomy. Each PC received fewer CFs than did age-matched controls and the maximal multi-reinnervation was reached on P7, 2 days later than in controls. Consequently, the onset of CF synapse elimination in reinnervated PCs was delayed, but then proceeded in parallel with controls so that all PCs were monoinnervated by P15. Furthermore, reinnervated PCs had delayed dendritic maturation and subsequent dendritic abnormalities consistent with the role of CF innervation in PC dendritic growth. Thus, within the olivocerebellar system, our data suggest that target neurons depend upon sufficient afferent investment arriving at the correct time for their normal development, and maturation of the target neuron regulates afferent selection and therefore circuit maturation. [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] 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] Long-lasting increased excitability differs in dentate gyrus vs.HIPPOCAMPUS, Issue 3 2002CA1 in freely moving chronic epileptic rats after electrically induced status epilepticus Abstract A paired-pulse (PP) stimulation protocol was used to examine changes in field potentials (fEPSPs), locally evoked in CA1 via Schaffer/commissural fiber stimulation and in the dentate gyrus (DG) through angular bundle stimulation, in freely moving epileptic rats. This epilepsy model is characterized by recurrent spontaneous seizures that occur after a latent period of 1,2 weeks following an electrically induced status epilepticus (SE). In the control period, i.e., before induction of SE, the PP stimulation protocol given at the appropriate intensity evoked fEPSPs with a pronounced paired-pulse depression (PPD). In the acute period, immediately after SE, the fEPSPs in the CA1 and DG areas were generally depressed. During the latent period in the CA1 stratum radiatum, the negative fEPSP was followed by a large positive potential that remained for the rest of the recording period. CA1 PPD, observed during the control period, was changed to paired-pulse facilitation (PPF) that remained for the rest of the recording period. Also during the latent period, a broad late component appeared in DG fEPSPs. The initial decrease in PPD was partly restored in the following weeks. Timm staining at different time points after SE showed an increase of mossy-fiber sprouting in the inner molecular layer within 6 days, which was robust within 6 weeks. We noted Timm granules positioned on parvalbumin immunoreactive neurons in the granule-cell layer of rats that had survived SE, suggesting that restoration of PPD could be partly due to reinnervation of a population of GABAergic neurons. The broad late component of DG fEPSPs, which was sensitive to the NMDA receptor antagonist ketamine, was still present for at least 6 weeks into the chronic epileptic phase, indicating lasting increased excitability. These observed changes indicate a lasting increased excitability in CA1 and DG networks that could play a role in the recurrence of spontaneous seizures. Hippocampus 2002;12:311,324. © 2002 Wiley-Liss, Inc. [source] Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Petrica-Adrian Panaite Abstract Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine ,-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission. © 2010 Wiley-Liss, Inc. [source] Morphometric analysis of canine skeletal muscles following experimental callus distraction according to the ilizarov methodJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2000Bernd Fink Muscle fiber diameter and fiber-type distribution were analyzed during callus distraction. The right tibia in 24 beagles was lengthened 2.5 cm by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, at a rate of two times for 0.5 mm per day. Twelve dogs that underwent limb-lengthening and three dogs in the control group that did not undergo limb-lengthening were killed at the end of the 25-day distraction phase (group A). The remaining dogs (12 that underwent limb-lengthening and three that did not) were killed after an additional consolidation period of 25 days (group B). The tibialis anterior, extensor digitorum longus, peroneus longus, and gastrocnemius muscles were removed from the right limb (which had undergone distraction) and the left control side of each animal. Crosscut cryostat sections were stained by adenosine triphosphatase at pH 4.3 and 9.4 to determine the size and distribution of types I and II fibers. Morphometric analysis of the muscle fibers was performed by a computer-assisted two-point technique. On the lengthened side, the muscles revealed marked atrophy affecting predominantly type-II fiber in the dogs in group A and affecting both fiber types in dogs in group B. Fiber density increased in both groups. In addition, fiber-type grouping indicative of reinnervation was obvious in group B. Fiber-type distribution in the dogs in group B showed a shift toward type I in the tibialis anterior (p = 0.043) and extensor digitorum longus (p = 0.034) muscles and a shift toward type II in the gastrocnemius (p = 0.038). The data show that tension-stress during tibial lengthening leads to atrophy of type-II fiber, reflecting disuse of muscle fiber in the distraction period as well as neurogenic atrophy followed by the reinnervation processes. Furthermore, the data are consistent with the occurrence of histoneogenesis during limb-lengthening resulting in an increase in fiber density. [source] Immunohistochemical and electron microscopic study of extrinsic hepatic reinnervation following orthotopic liver transplantation in ratsLIVER INTERNATIONAL, Issue 5 2001Tsuyoshi Takahashi Abstract:Background/Aims: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. Methods: Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). Results: Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. Conclusion: The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats. [source] Evidence for target-specific outgrowth from subpopulations of grafted human dopamine neuronsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2001Ingrid Strömberg Abstract Clinical and experimental grafting in Parkinson's disease has shown the need for enhanced survival of dopamine neurons to obtain improved functional recovery. In addition, it has been suggested that a limited number of surviving dopamine neurons project to the dopamine-denervated host striatum. The aim of this study was to investigate if subpopulations of ventral mesencephalic dopamine neurons project to their normal targets, i.e., dorsal vs. ventral striatum. Following implantation of human ventral mesencepahlic tissue into the lateral ventricle of dopamine-depleted rats, human-derived dopamine reinnervation was achieved both in dorsal and ventral striatum. Treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) resulted in a degeneration of tyrosine hydroxylase (TH)-immunoreactive nerve fibers in dorsal striatum but not in ventral areas in some animals, while MPTP was without effect in other animals. TH-immunoreactive neurons were small and appeared shrunken in animals carrying grafts affected by the MPTP treatment. In conclusion, grafted dopamine neurons projected nerve fibers into areas that they normally innervate. Thus, when searching for factors that may enhance survival of grafted dopamine neurons it is important to study which subpopulation(s) of ventral mesencephalic dopamine neurons is affected, such that a proper reinnervation may be achieved. Microsc. Res. Tech. 54:287,297, 2001. © 2001 Wiley-Liss, Inc. [source] Long-term morphometric and immunohistochemical findings in human free microvascular muscle flaps,MICROSURGERY, Issue 1 2004M. Susanna C. Kauhanen M.D., Ph.D. Reinnervation, muscle regeneration, density of microvessels, and muscle-type specific atrophy were studied 3,4 years after surgery in surgically nonreinnervated free microvascular muscle flaps to 13 patients transplanted to the upper or lower extremities. Routine histology and immunohistochemistry for PGP 9.5 and S-100 (neuronal markers), Ki-67 (cell proliferation), myosin (muscle fiber types), and CD-31 (endothelium) were carried out, and results were analyzed morphometrically. Three to 4 years after surgery, severe atrophy of predominantly slow-type fibers was seen in 9 cases. In 4 cases, muscle-fiber diameter and fiber-type distribution were close to normal. Long intraoperative muscle ischemia and postoperative immobilization were associated with poor muscle bulk in flaps. The density of microvessels in flaps did not differ from control muscles. PGP 9.5 and S-100 immunopositive nerve fibers were detected in 7 patients. Reinnervation was associated with good muscle bulk. In 4 patients, activation of satellite cells was evident. The results suggest that in some cases, spontaneous reinnervation may occur in free muscle flaps, and that several years after microvascular free flap transfer, the muscle still attempts to regenerate. © 2004 Wiley-Liss, Inc. [source] Opportunities afforded by the study of unmyelinated nerves in skin and other organsMUSCLE AND NERVE, Issue 6 2004William R. Kennedy MS Abstract Neurological practice is mainly focused on signs and symptoms of disorders that involve functions governed by myelinated nerves. Functions controlled by unmyelinated nerve fibers have necessarily remained in the background because of the inability to consistently stain, image, or construct clinically applicable neurophysiological tests of these nerves. The situation has changed with the introduction of immunohistochemical methods and confocal microscopy into clinical medicine, as these provide clear images of thin unmyelinated nerves in most organs. One obvious sign of change is the increasing number of reports from several laboratories of the pathological alterations of cutaneous nerves in skin biopsies from patients with a variety of clinical conditions. This study reviews recent methods to stain and image unmyelinated nerves as well as the use of these methods for diagnosing peripheral neuropathy, for experimental studies of denervation and reinnervation in human subjects, and for demonstrating the vast array of unmyelinated nerves in internal organs. The new ability to examine the great variety of nerves in different organs opens opportunities and creates challenges and responsibilities for neurologists and neuroscientists. Muscle Nerve 756,767, 2004 [source] Sphincter electromyography and multiple system atrophyMUSCLE AND NERVE, Issue 1 2003Frederick Nahm MD Abstract Electromyographic studies of the sphincter in patients with multiple system atrophy have shown increased duration and polyphasia of motor unit potentials. These electrophysiological markers have been used to argue for the selective degeneration of sacral motor neurons in Onuf's nucleus in patients with multiple system atrophy. Studies comparing sphincter electromyographic changes in patients with multiple system atrophy and Parkinson's disease have shown significant differences between these two patient populations. Despite the controversy surrounding this claim, recent studies using quantitative electromyographic techniques support the view that reinnervation of the anal sphincter muscles may be a useful diagnostic marker for distinguishing multiple system atrophy from Parkinson's disease. A critical review of these data is needed to assess the validity and reliability of electromyographic changes in multiple system atrophy. © 2003 Wiley Periodicals, Inc. Muscle Nerve 28: 18,26, 2003 [source] How selective is the reinnervation of skeletal muscle fibers?MUSCLE AND NERVE, Issue 6 2002V. Reggie Edgerton PhD No abstract is available for this article. [source] Changes in a rat facial muscle after facial nerve injury and repairMUSCLE AND NERVE, Issue 9 2001Davor Jergovi Abstract This study describes changes in a rat facial muscle innervated by the mandibular and buccal facial nerve branches 4 months after nerve injury and repair. The following groups were studied: (A) normal controls; (B) spontaneous reinnervation by collateral or terminal sprouting; (C) reinnervation after surgical repair of the mandibular branch; and (D) chronic denervation. The normal muscle contained 1200 exclusively fast fibers, mainly myosin heavy chain (MyHC) IIB fibers. In group B, fiber number and fiber type proportions were normal. In group C, fiber number was subnormal. Diameters and proportions of MyHC IIA and hybrid fibers were above normal. The proportion of MyHC IIB fibers was subnormal. Immediate and delayed repair gave similar results with respect to the parameters examined. Group D rats underwent severe atrophic and degenerative changes. Hybrid fibers prevailed. These data suggest that spontaneous regeneration of the rat facial nerve is superior to regeneration after surgical repair and that immediacy does not give better results than moderate delay with respect to surgical repair. Long delays are shown to be detrimental. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1202,1212, 2001 [source] Sprouting capacity of lumbar motoneurons in normal and hemisected spinal cords of the ratTHE JOURNAL OF PHYSIOLOGY, Issue 15 2010T. Gordon Nerve sprouting to reinnervate partially denervated muscles is important in several disease and injury states. To examine the effectiveness of sprouting of active and inactive motor units (MUs) and the basis for a limit to sprouting, one of three rat lumbar spinal roots was cut under normal conditions and when the spinal cord was hemisected at T12. Muscle and MU isometric contractile forces were recorded and muscle fibres in glycogen-depleted single muscle units enumerated 23 to 380 days after surgery. Enlargement of intact MUs by sprouting was effective in compensating for up to 80% loss of innervation. For injuries that removed >70,80% of the intact MUs, muscle contractile force and weight dropped sharply. For partial denervation of <70%, all MUs increased contractile force by the same factor in both normally active muscles and muscles whose activity was reduced by T12 hemisection. Direct measurements of MU size by counting glycogen-depleted muscle fibres in physiologically and histochemically defined muscle units, provided direct evidence for a limit in MU size, whether or not the activity of the muscles was reduced by spinal cord hemisection. Analysis of spatial distribution of muscle fibres within the outer boundaries of the muscle unit demonstrated a progressive increase in fibres within the territory to the limit of sprouting when most of the muscle unit fibres were adjacent to each other. We conclude that the upper limit of MU enlargement may be explained by the reinnervation of denervated muscle fibres by axon sprouts within the spatial territory of the muscle unit, formerly distributed in a mosaic pattern. [source] Improvement of respiratory compromise through abductor reinnervation and pacing in a patient with bilateral vocal fold impairment,THE LARYNGOSCOPE, Issue 1 2010Michael Broniatowski MD Abstract Objectives/Hypothesis. To determine whether respiratory compromise from bilateral vocal fold impairment (paralysis) can be objectively alleviated by reinnervation and pacing. Methods. A patient with paramedian vocal folds and synkinesis had a tracheotomy for stridor after bilateral laryngeal nerve injury and Miller Fisher syndrome. One posterior cricoarytenoideus (PCA) received a nerve-muscle pedicle fitted with a perineural electrode for pacemaker stimulation. The airway was evaluated endoscopically and by spirometry for up to 1 year. Results. Bilateral vocal fold patency during quiet breathing was reversed to active vocal fold adduction during tracheal occlusion. Peak inspiratory flows (PIFs) were significantly higher (P < .001) after reinnervation. PIFs and glottic apertures increased further under stimulation (42 Hz, 1,4 mA, 42,400 ,sec). although the differences were not significant. Conclusions. Based on our preliminary data, PCA reinnervation and pacing offer promise for amelioration of respiratory compromise after paradoxical adduction in bilateral vocal fold impairment. Laryngoscope, 2010 [source] Quantitative Assessment of Laryngeal Muscle Morphology After Recurrent Laryngeal Nerve Injury: Right vs.THE LARYNGOSCOPE, Issue 10 2008Left Differences Abstract Objectives/Hypothesis: Reports of laryngeal response to denervation are inconsistent. Some document atrophy and fibrosis in denervated laryngeal muscles, whereas others indicate resistance to atrophy. Spontaneous reinnervation has also been documented. The goal of this study was to clarify the effects of nerve injury and reinnervation on thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Study Design: Laboratory experiment. Methods: TA and PCA muscles of cats were harvested 5 to 6 months after transecting right or left recurrent laryngeal nerve (RLN). Images of muscle cross-sections were acquired and studied using an image analysis workstation. Cross-sectional areas as well as total cross-sectional area of randomly selected muscle fibers were recorded. Results: TA reinnervation was robust on both sides, but there was less reinnervation of the PCA muscle after left-sided RLN lesion than after right-sided injury. Conclusions: Differences in reinnervation after RLN injury could contribute to the higher clinical incidence of left- vs. right-sided laryngeal paralysis. [source] Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx,THE LARYNGOSCOPE, Issue 7 2008Stacey L. Halum MD Abstract Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation-induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors. Study Design: Animal experiment. Methods: Unilateral RLN transection and sternocleidomastoid muscle (,1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral-enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10,5 M], insulin-like growth factor-1 [(IGF- 1) 100 ,g/mL], ciliary neurotrophic factor [(CNTF) 50 ,g/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival. Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF-1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival. Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF-1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion. [source] Laryngeal Abscess after Injection Laryngoplasty with Micronized AlloDerm,THE LARYNGOSCOPE, Issue 9 2004Philip E. Zapanta MD Objective: Patients with unilateral vocal cord paralysis usually present with dysphonia and occasionally with swallowing problems. Operative management includes thyroplasty type I, injection laryngoplasty, arytenoid adduction, and reinnervation. Recent publications have documented the safety of micronized AlloDerm (Cymetra, LifeCell Corporation, Branchburg, NJ) for injection laryngoplasty, but we report the first documented case of a laryngeal abscess after injection laryngoplasty with Cymetra. Study Design: Single case report of a laryngeal abscess after injection laryngoplasty with Cymetra. Methods: The patient's clinical course is presented and discussed, and the pertinent literature is reviewed. Results: Prompt hospital admission with intravenous antibiotics and steroids resolved this airway emergency. Follow-up visits showed a significantly improved postoperative voice with an intact airway. Conclusion: A review of the literature reveals that this case of a laryngeal abscess after injection laryngoplasty with Cymetra is the first of its kind. Studies have shown that the use of AlloDerm in the head and neck region is safe, but otolaryngologists need to be cognizant of potential complications when working with this material. [source] Timing of Human Insulin-Like Growth Factor-1 Gene Transfer in Reinnervating Laryngeal Muscle,THE LARYNGOSCOPE, Issue 4 2004Hideki Nakagawa MD Abstract Objectives/Hypothesis The authors have designed a rat laryngeal paralysis model to study gene transfer strategies using a muscle-specific expression system to enhance local delivery of human insulin-like growth factor-1 (hIGF-1). In preliminary studies, a nonviral vector containing the ,-actin promoter and human hIGF-1 sequence produced both neurotrophic and myotrophic effects 1 month after single injection of plasmid formulation into paralyzed rat thyroarytenoid muscle in vivo. Based on these findings, it is hypothesized that the effects of hIGF-1 will enhance the results of laryngeal muscle innervation procedures. The timing of gene delivery relative to nerve repair is likely to be important, to optimize the results. Study Design Prospective analysis. Methods The effects of nonviral gene transfer for the delivery of hIGF-1 were evaluated in rats treated immediately following recurrent laryngeal nerve transection and repair and in rats receiving a delayed treatment schedule, 30 days after nerve transection and repair. Gene transfer efficiency was determined using polymerase chain reaction and reverse transcriptase,polymerase chain reaction techniques. Muscle fiber diameter, motor endplate length, and percentage of motor endplates with nerve contact were examined to assess hIGF-1 trophic effects. Results Compared with reinnervated untreated control samples, both early and delayed hIGF-1 transfer resulted in significant increase in muscle fiber diameter. Motor endplate length was significantly decreased and nerve/motor endplate contact was significantly increased following delayed gene transfer, but not after early treatment. Conclusion We infer from results of the study that delayed hIGF-1 gene transfer delivered by a single intramuscular injection will enhance the process of muscle reinnervation. The clinical relevance of these findings supports the future application of gene therapy using nonviral vectors for management of laryngeal paralysis and other peripheral nerve injuries. [source] Morphologic Correlates for Laryngeal Reinnervation,THE LARYNGOSCOPE, Issue 11 2001Richard R. Gacek MD Abstract Objective To describe morphologic correlates for laryngeal reinnervation. Study Design Review of anatomic experiments dealing with laryngeal innervation performed over a 25-year period. Methods Description of results from experimental studies on the cat and human laryngeal muscles and nerve supply. Results Despite separation of abductor and adductor laryngeal motor neurons in the central nervous system, the mixture of abductor and adductor axons in the recurrent laryngeal nerve indicates that selective re-innervation of an individual laryngeal muscle must be accomplished at the neuromuscular junction (NMJ) of the muscle. The optimal time for a reinnervating neural source to re-occupy vacated NMJ is at the time of denervation. If the reinnervation procedure is attempted long (>1 mo) after denervation, extraneous end plates of other neural systems must be eliminated to provide vacant NMJ. The nerve muscle pedicle (NMP) concept is an effective model for reinnervation of a laryngeal muscle provided its activity pattern is similar to that of the denervated muscle and its insertion into vacated NMJ is timely. Conclusion NMP offers a logical method for selective laryngeal muscle reinnervation. Critical to the success of NMP are the physiological input to the NMP and timing of NMP implantation. [source] Effect of weak, interrupted sinusoidal low frequency magnetic field on neural regeneration in rats: Functional evaluationBIOELECTROMAGNETICS, Issue 5 2005Marijan Bervar Abstract A study of the effect of weak, interrupted sinusoidal low frequency magnetic field (ISMF) stimulation on regeneration of the rat sciatic nerve was carried out. In the experiment, 60 Wistar rats were used: 24 rats underwent unilateral sciatic nerve transection injury and immediate surgical nerve repair, 24 rats underwent unilateral sciatic nerve crush injury, and the remaining 12 rats underwent a sham surgery. Half of the animals (n,=,12) with either sciatic nerve lesion were randomly chosen and exposed between a pair of Helmholtz coils for 3 weeks post-injury, 4 h/day, to an interrupted (active period to pause ratio,=,1.4 s/0.8 s) sinusoidal 50 Hz magnetic field of 0.5 mT. The other half of the animals (n,=,12) and six rats with sham surgery were used for two separate controls. Functional recovery was followed for 6 weeks for the crush injuries and 7½ months for the transection injuries by video assisted footprint analysis in static conditions and quantified using a recently revised static sciatic index (SSI) formula. We ascertained that the magnetic field influence was weak, but certainly detectable in both injury models. The accuracy of ISMF influence detection, determined by the one-way repeated measures ANOVA test, was better for the crush injury model: F(1, 198),=,9.0144, P,=,.003, than for the transection injury model: F(1, 198),=,6.4826, P,=,.012. The Student,Newman,Keuls range test for each response day yielded significant differences (P,<,.05) between the exposed and control groups early in the beginning of functional recovery and later on from the points adjacent to the beginning of the plateau, or 95% of functional recovery, and the end of observation. These differences probably reflect the ISMF systemic effect on the neuron cell bodies and increased and more efficient reinnervation of the periphery. Bioelectromagnetics 26:351,356, 2005. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||