The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Douglas E. Wright - One of the best experts on this subject based on the ideXlab platform.
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the effect of exercise on neuropathic symptoms nerve function and Cutaneous Innervation in people with diabetic peripheral neuropathy
Journal of Diabetes and Its Complications, 2012Co-Authors: Patricia M Kluding, Mamatha Pasnoor, Rupali Singh, Stephen Jernigan, Kevin L Farmer, Jason Rucker, Neena K Sharma, Douglas E. WrightAbstract:Abstract Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and Cutaneous Innervation. Methods A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4 ± 5.98; duration of diabetes 12.4 ± 12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Results Significant reductions in pain (− 18.1 ± 35.5 mm on a 100 mm scale, P = .05), neuropathic symptoms (− 1.24 ± 1.8 on MNSI, P = .01), and increased intraepidermal nerve fiber branching (+ 0.11 ± 0.15 branch nodes/fiber, P = .008) from a proximal skin biopsy were noted following the intervention. Conclusions This is the first study to describe improvements in neuropathic and Cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies.
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selective changes in nocifensive behavior despite normal Cutaneous axon Innervation in leptin receptor null mutant db db mice
Journal of The Peripheral Nervous System, 2007Co-Authors: Douglas E. Wright, Megan S. Johnson, Melinda G. Arnett, Susan E. Smittkamp, Janelle M. RyalsAbstract:Much of our understanding of the effects of diabetes on the peripheral nervous system is derived from models induced by streptozotocin in which hyperglycemia is rapidly caused by pancreatic beta-cell destruction. Here, we have quantified sensory impairments over time in leptin receptor (lepr)–null mutant (−/−) mice, a type 2 model of diabetes in which the absence of leptin receptor signaling leads to obesity and chronic hyperglycemia by 4 weeks of age. To assess these mice as a model for peripheral neuropathy, we quantified the responsiveness of lepr (−/−) mice to mechanical, thermal, and chemogenic stimuli, as well as epidermal and dermal Innervation of the hind paw. Compared with wild-type (+/+) and heterozygous (+/−) mice, lepr (−/−) mice displayed reduced sensitivity to mechanical stimuli by 6 weeks of age, and however, responses to noxious heat were normal. Lepr (−/−) mice also devoted less activity to their injected paw during the second phase following formalin administration. However, epidermal and dermal Innervation of lepr (−/−) mice was not different from that of lepr (+/+) and (+/−) mice even after 10 weeks of hyperglycemia, suggesting that Cutaneous Innervation is resistant to chronic hyperglycemia in these mice. These results suggest that certain rodent nocifensive behaviors may be linked to the abundance of Cutaneous Innervation, while others are not. Finally, these results reveal that the lepr (−/−) mice may not be useful to study neuropathy associated with distal axonal degeneration but may be better suited for studies of hyperglycemia-induced sensory neuron dysfunction without distal nerve loss.
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Selective changes in nocifensive behavior despite normal Cutaneous axon Innervation in leptin receptor–null mutant (db/db) mice
Journal of the peripheral nervous system : JPNS, 2007Co-Authors: Douglas E. Wright, Megan S. Johnson, Melinda G. Arnett, Susan E. Smittkamp, Janelle M. RyalsAbstract:Much of our understanding of the effects of diabetes on the peripheral nervous system is derived from models induced by streptozotocin in which hyperglycemia is rapidly caused by pancreatic beta-cell destruction. Here, we have quantified sensory impairments over time in leptin receptor (lepr)–null mutant (−/−) mice, a type 2 model of diabetes in which the absence of leptin receptor signaling leads to obesity and chronic hyperglycemia by 4 weeks of age. To assess these mice as a model for peripheral neuropathy, we quantified the responsiveness of lepr (−/−) mice to mechanical, thermal, and chemogenic stimuli, as well as epidermal and dermal Innervation of the hind paw. Compared with wild-type (+/+) and heterozygous (+/−) mice, lepr (−/−) mice displayed reduced sensitivity to mechanical stimuli by 6 weeks of age, and however, responses to noxious heat were normal. Lepr (−/−) mice also devoted less activity to their injected paw during the second phase following formalin administration. However, epidermal and dermal Innervation of lepr (−/−) mice was not different from that of lepr (+/+) and (+/−) mice even after 10 weeks of hyperglycemia, suggesting that Cutaneous Innervation is resistant to chronic hyperglycemia in these mice. These results suggest that certain rodent nocifensive behaviors may be linked to the abundance of Cutaneous Innervation, while others are not. Finally, these results reveal that the lepr (−/−) mice may not be useful to study neuropathy associated with distal axonal degeneration but may be better suited for studies of hyperglycemia-induced sensory neuron dysfunction without distal nerve loss.
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Restorative effects of neurotrophin treatment on diabetes-induced Cutaneous axon loss in mice.
Experimental neurology, 2003Co-Authors: Julie A. Christianson, John T. Riekhof, Douglas E. WrightAbstract:Chronic hyperglycemia in diabetes causes a variety of somatosensory deficits, including reduced Cutaneous Innervation of distal extremities. Deficient neurotrophin support has been proposed to contribute to the development of diabetic neuropathy. Here, studies were carried out in streptozotocin (STZ)-treated mice to determine whether (1) Cutaneous Innervation deficits develop in response to hyperglycemia, (2) neurotrophin production is altered in the skin, and (3) neurotrophin treatment improves Cutaneous Innervation deficits. Cutaneous Innervation was quantified in the hindlimb skin using antibodies that label nerve growth factor- (NGF) responsive (CGRP), glial cell line-derived neurotrophic factor (GDNF)/neurturin (NTN) -responsive (P2X(3)), or all Cutaneous axons (PGP 9.5). Diabetic mice displayed severely reduced Cutaneous Innervation for all three antibodies in both flank and footpad skin regions, similar to reports of Cutaneous Innervation loss in human diabetic patients. Qualitative assessment of mRNAs for NGF, GDNF, and NTN demonstrated that these mRNAs were expressed in hindlimb flank and footpad skin from diabetic mice. Next, diabetic mice were then treated intrathecally for 2 weeks with NGF, GDNF, or NTN. NGF treatment failed to improve Cutaneous Innervation, but stimulated axon branching. In comparison, GDNF and NTN treatment increased Cutaneous Innervation and axon branching. Our results reveal that similar to human diabetic patients, STZ-induced diabetes significantly reduces hindlimb Cutaneous Innervation in mice. Importantly, intrathecal treatment using GDNF or NTN strongly stimulated axon growth and branching, suggesting that administration of these trophic factors can improve Cutaneous Innervation deficits caused by diabetes.
Justin C. Mcarthur - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Cutaneous Innervation by skin biopsies.
Current opinion in neurology, 2001Co-Authors: John W. Griffin, Justin C. Mcarthur, Michael PolydefkisAbstract:Skin biopsies that are immunostained to identify nerve fibers provide a new tool for assessing the small caliber nociceptors that terminate in the epidermis, as well as other Cutaneous nerve fibers. Skin biopsies can be performed in multiple sites and can be repeated over time, so that a spatiotemporal profile of epidermal Innervation can be constructed. This approach may help assess the progression of fiber loss in disease and of regeneration and re-Innervation with treatment.
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Quantitative analysis of epidermal Innervation in Fabry disease
Neurology, 1999Co-Authors: L.j. C. Scott, John W. Griffin, Carlos A. Luciano, Norman W. Barton, Tapas K. Banerjee, Thomas O. Crawford, Justin C. Mcarthur, A. Tournay, Raphael SchiffmannAbstract:Objective: To use skin biopsy specimens to quantitate the Cutaneous Innervation density of Fabry patients who had preserved renal function. Background: The small fiber neuropathy of Fabry disease is difficult to detect and quantitate by conventional methods. Because this neuropathy is a common characteristic of Fabry disease, quantitating changes in this parameter would be helpful in demonstrating the effectiveness of enzyme or gene replacement therapy. Methods: Patients underwent skin biopsy at the thigh and foot. Innervation density was determined by counting free nerve endings in the epidermis. These data were compared with nerve conduction studies, and in selected patients, fiber quantitation of sural nerve biopsy specimens. Results: The Fabry patients had normal results of nerve conduction studies and large fiber quantitation by sural nerve biopsy. However, the involvement of small Cutaneous fibers in these patients was easily demonstrable and quantifiable by skin biopsy. All patients showed severe loss of intraepidermal Innervation at the ankle, but fiber loss at the distal thigh was proportionately less severe. Conclusions: The nerve damage in Fabry patients with preserved renal function involves exclusively small myelinated and unmyelinated fibers, and skin biopsy is a useful in detecting and quantitating such damage. Comparison of Cutaneous Innervation density with quantitation of sural nerve biopsy specimens demonstrated that skin biopsy specimens were as sensitive in detecting the presence of neuropathy as were the nerve specimens. It is speculated that analysis of Cutaneous Innervation may provide a useful marker of the nervous system’s response to specific therapy for Fabry disease.
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Cutaneous Innervation in sensory neuropathies evaluation by skin biopsy
Neurology, 1995Co-Authors: B G Mccarthy, Sung-tsang Hsieh, John W. Griffin, Adelaine Stocks, Peter Hauer, C Macko, David R Cornblath, Justin C. McarthurAbstract:Objective: To use punch skin biopsies to evaluate the loss of intra-epidermal nerve fibers in sensory neuropathies. Background: Previous assessments of epidermal nerve fibers have been constrained by relatively insensitive staining techniques and variability in quantification. Methods: Punch skin biopsies were performed on the heel and leg of HIV-seronegative controls, HIV-seropositive individuals without neuropathy, and patients with sensory neuropathies, including HIV-seronegative and HIV-positive individuals. After formalin fixation, 50-micro meter free-floating sections were stained with a monoclonal antibody to neuron-specific ubiquitin hydrolase, PGP9.5. The number of intraepidermal fibers/mm in at least three sections from each patient was counted by one observer blinded to site and clinical status. Results: Dermal and epidermal nerve fibers were readily identified and quantified. The immunostaining technique reliably demonstrated a dermal plexus of myelinated and unmyelinated fibers parallel to the surface of the skin. In the epidermis, unmyelinated fibers ascended vertically between the keratinocytes to reach the stratum corneum. The number of intra-epidermal fibers/mm in the distal leg (mean plus minus SEM) was 17.84 plus minus 3.03 in seven HIV-seronegative controls. Epidermal fiber number was significantly reduced (p equals 0.01) in five HIV-infected patients with sensory neuropathies associated with didanosine or zalcitabine therapy (1.07 plus minus 0.40) and in eight HIV-seronegative patients with sensory neuropathies (3.1 plus minus 3.1). Four of five neurologically normal HIV-seropositive subjects had reduced numbers of epidermal fibers, suggesting a subclinical neuropathy. Serial biopsies in one individual demonstrated the evolution of degenerating epidermal fibers after development of zalcitabine-induced sensory neuropathy. Conclusion: Skin biopsies stained with the sensitive panaxonal marker anti-PGP9.5 demonstrated significant reduction in intraepidermal fibers in sensory neuropathies. This simple and repeatable technique is a reliable method for quantitation of small Cutaneous sensory fibers. In addition, skin biopsies may be useful in assessing the course and spatial distribution of involvement in peripheral nerve disease. NEUROLOGY 1995;45: 1848-1855
Janelle M. Ryals - One of the best experts on this subject based on the ideXlab platform.
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selective changes in nocifensive behavior despite normal Cutaneous axon Innervation in leptin receptor null mutant db db mice
Journal of The Peripheral Nervous System, 2007Co-Authors: Douglas E. Wright, Megan S. Johnson, Melinda G. Arnett, Susan E. Smittkamp, Janelle M. RyalsAbstract:Much of our understanding of the effects of diabetes on the peripheral nervous system is derived from models induced by streptozotocin in which hyperglycemia is rapidly caused by pancreatic beta-cell destruction. Here, we have quantified sensory impairments over time in leptin receptor (lepr)–null mutant (−/−) mice, a type 2 model of diabetes in which the absence of leptin receptor signaling leads to obesity and chronic hyperglycemia by 4 weeks of age. To assess these mice as a model for peripheral neuropathy, we quantified the responsiveness of lepr (−/−) mice to mechanical, thermal, and chemogenic stimuli, as well as epidermal and dermal Innervation of the hind paw. Compared with wild-type (+/+) and heterozygous (+/−) mice, lepr (−/−) mice displayed reduced sensitivity to mechanical stimuli by 6 weeks of age, and however, responses to noxious heat were normal. Lepr (−/−) mice also devoted less activity to their injected paw during the second phase following formalin administration. However, epidermal and dermal Innervation of lepr (−/−) mice was not different from that of lepr (+/+) and (+/−) mice even after 10 weeks of hyperglycemia, suggesting that Cutaneous Innervation is resistant to chronic hyperglycemia in these mice. These results suggest that certain rodent nocifensive behaviors may be linked to the abundance of Cutaneous Innervation, while others are not. Finally, these results reveal that the lepr (−/−) mice may not be useful to study neuropathy associated with distal axonal degeneration but may be better suited for studies of hyperglycemia-induced sensory neuron dysfunction without distal nerve loss.
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Selective changes in nocifensive behavior despite normal Cutaneous axon Innervation in leptin receptor–null mutant (db/db) mice
Journal of the peripheral nervous system : JPNS, 2007Co-Authors: Douglas E. Wright, Megan S. Johnson, Melinda G. Arnett, Susan E. Smittkamp, Janelle M. RyalsAbstract:Much of our understanding of the effects of diabetes on the peripheral nervous system is derived from models induced by streptozotocin in which hyperglycemia is rapidly caused by pancreatic beta-cell destruction. Here, we have quantified sensory impairments over time in leptin receptor (lepr)–null mutant (−/−) mice, a type 2 model of diabetes in which the absence of leptin receptor signaling leads to obesity and chronic hyperglycemia by 4 weeks of age. To assess these mice as a model for peripheral neuropathy, we quantified the responsiveness of lepr (−/−) mice to mechanical, thermal, and chemogenic stimuli, as well as epidermal and dermal Innervation of the hind paw. Compared with wild-type (+/+) and heterozygous (+/−) mice, lepr (−/−) mice displayed reduced sensitivity to mechanical stimuli by 6 weeks of age, and however, responses to noxious heat were normal. Lepr (−/−) mice also devoted less activity to their injected paw during the second phase following formalin administration. However, epidermal and dermal Innervation of lepr (−/−) mice was not different from that of lepr (+/+) and (+/−) mice even after 10 weeks of hyperglycemia, suggesting that Cutaneous Innervation is resistant to chronic hyperglycemia in these mice. These results suggest that certain rodent nocifensive behaviors may be linked to the abundance of Cutaneous Innervation, while others are not. Finally, these results reveal that the lepr (−/−) mice may not be useful to study neuropathy associated with distal axonal degeneration but may be better suited for studies of hyperglycemia-induced sensory neuron dysfunction without distal nerve loss.
John W. Griffin - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Cutaneous Innervation by skin biopsies.
Current opinion in neurology, 2001Co-Authors: John W. Griffin, Justin C. Mcarthur, Michael PolydefkisAbstract:Skin biopsies that are immunostained to identify nerve fibers provide a new tool for assessing the small caliber nociceptors that terminate in the epidermis, as well as other Cutaneous nerve fibers. Skin biopsies can be performed in multiple sites and can be repeated over time, so that a spatiotemporal profile of epidermal Innervation can be constructed. This approach may help assess the progression of fiber loss in disease and of regeneration and re-Innervation with treatment.
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Quantitative analysis of epidermal Innervation in Fabry disease
Neurology, 1999Co-Authors: L.j. C. Scott, John W. Griffin, Carlos A. Luciano, Norman W. Barton, Tapas K. Banerjee, Thomas O. Crawford, Justin C. Mcarthur, A. Tournay, Raphael SchiffmannAbstract:Objective: To use skin biopsy specimens to quantitate the Cutaneous Innervation density of Fabry patients who had preserved renal function. Background: The small fiber neuropathy of Fabry disease is difficult to detect and quantitate by conventional methods. Because this neuropathy is a common characteristic of Fabry disease, quantitating changes in this parameter would be helpful in demonstrating the effectiveness of enzyme or gene replacement therapy. Methods: Patients underwent skin biopsy at the thigh and foot. Innervation density was determined by counting free nerve endings in the epidermis. These data were compared with nerve conduction studies, and in selected patients, fiber quantitation of sural nerve biopsy specimens. Results: The Fabry patients had normal results of nerve conduction studies and large fiber quantitation by sural nerve biopsy. However, the involvement of small Cutaneous fibers in these patients was easily demonstrable and quantifiable by skin biopsy. All patients showed severe loss of intraepidermal Innervation at the ankle, but fiber loss at the distal thigh was proportionately less severe. Conclusions: The nerve damage in Fabry patients with preserved renal function involves exclusively small myelinated and unmyelinated fibers, and skin biopsy is a useful in detecting and quantitating such damage. Comparison of Cutaneous Innervation density with quantitation of sural nerve biopsy specimens demonstrated that skin biopsy specimens were as sensitive in detecting the presence of neuropathy as were the nerve specimens. It is speculated that analysis of Cutaneous Innervation may provide a useful marker of the nervous system’s response to specific therapy for Fabry disease.
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Cutaneous Innervation in sensory neuropathies evaluation by skin biopsy
Neurology, 1995Co-Authors: B G Mccarthy, Sung-tsang Hsieh, John W. Griffin, Adelaine Stocks, Peter Hauer, C Macko, David R Cornblath, Justin C. McarthurAbstract:Objective: To use punch skin biopsies to evaluate the loss of intra-epidermal nerve fibers in sensory neuropathies. Background: Previous assessments of epidermal nerve fibers have been constrained by relatively insensitive staining techniques and variability in quantification. Methods: Punch skin biopsies were performed on the heel and leg of HIV-seronegative controls, HIV-seropositive individuals without neuropathy, and patients with sensory neuropathies, including HIV-seronegative and HIV-positive individuals. After formalin fixation, 50-micro meter free-floating sections were stained with a monoclonal antibody to neuron-specific ubiquitin hydrolase, PGP9.5. The number of intraepidermal fibers/mm in at least three sections from each patient was counted by one observer blinded to site and clinical status. Results: Dermal and epidermal nerve fibers were readily identified and quantified. The immunostaining technique reliably demonstrated a dermal plexus of myelinated and unmyelinated fibers parallel to the surface of the skin. In the epidermis, unmyelinated fibers ascended vertically between the keratinocytes to reach the stratum corneum. The number of intra-epidermal fibers/mm in the distal leg (mean plus minus SEM) was 17.84 plus minus 3.03 in seven HIV-seronegative controls. Epidermal fiber number was significantly reduced (p equals 0.01) in five HIV-infected patients with sensory neuropathies associated with didanosine or zalcitabine therapy (1.07 plus minus 0.40) and in eight HIV-seronegative patients with sensory neuropathies (3.1 plus minus 3.1). Four of five neurologically normal HIV-seropositive subjects had reduced numbers of epidermal fibers, suggesting a subclinical neuropathy. Serial biopsies in one individual demonstrated the evolution of degenerating epidermal fibers after development of zalcitabine-induced sensory neuropathy. Conclusion: Skin biopsies stained with the sensitive panaxonal marker anti-PGP9.5 demonstrated significant reduction in intraepidermal fibers in sensory neuropathies. This simple and repeatable technique is a reliable method for quantitation of small Cutaneous sensory fibers. In addition, skin biopsies may be useful in assessing the course and spatial distribution of involvement in peripheral nerve disease. NEUROLOGY 1995;45: 1848-1855
Christelle Le Gall-ianotto - One of the best experts on this subject based on the ideXlab platform.
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In vitro models to study Cutaneous Innervation mechanisms
Skin Tissue Models for Regenerative Medicine, 2018Co-Authors: Nicolas Lebonvallet, Jérémy Chéret, Christelle Le Gall-ianotto, Raphael Leschiera, Matthieu Talagas, Raphaele Le Garrec, Virginie Buhé, Killian L’herondelle, Olivier Gouin, Mehdi SakkaAbstract:Abstract The skin is densely innervated to transmit all sensations (touch, temperature, pressure, pain, and pruritus) but not only it. Indeed, Innervation plays a major role in the structuration of the epidermis, in its renewal, and in the process as wound healing. There are increasing evidences that skin cells and Cutaneous nerve endings are in close interactions each other. So, to study them is an important issue to better understand the behavior of the skin and its both physiological and pathological processes. However, due to scientific, technical, ethical, or economic reasons, the study of these interactions in human or animals in vivo remains quite impossible. So, the development of in vitro models is crucial to better understand them. Since several years, all the actors of these interactions, skin cells such as keratinocytes, fibroblasts, melanocytes, Merkel cells or stem cells, and sensory neurons, could be extracted and cultured independently or together so named 2-D cocultures. Other cocultures, the 3-D cocultures, could also be considered by the use of the epidermis or dermis or whole portions of native or reconstructed skin. These 3-D models offer also an alternative by the use of compartmented cocultures to only analyze the biochemical communication between the different types of cells. After a description of the different models available, this chapter will give some clues to define the best model(s) depending of the applications and, finally, will discuss of the advantages and the limitations of these types of cultures to study Cutaneous Innervation mechanisms.
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Role of neuropeptides, neurotrophins, and neurohormones in skin wound healing.
Wound Repair and Regeneration, 2013Co-Authors: Jérémy Chéret, Nicolas Lebonvallet, Jean-luc Carré, Laurent Misery, Christelle Le Gall-ianottoAbstract:: Due to the close interactions between the skin and peripheral nervous system, there is increasing evidence that the Cutaneous Innervation is an important modulator of the normal wound healing process. The communication between sensory neurons and skin cells involves a variety of molecules (neuropeptides, neurohormones, and neurotrophins) and their specific receptors expressed by both neuronal and nonneuronal skin cells. It is well established that neurotransmitters and nerve growth factors released in skin have immunoregulatory roles and can exert mitogenic actions; they could also influence the functions of the different skin cell types during the wound healing process.
