The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform

Robert M. Hoffman - One of the best experts on this subject based on the ideXlab platform.

  • nestin expressing hair follicle associated pluripotent hap stem cells promote whisker sensory Nerve growth in long term 3d gelfoam histoculture
    Methods of Molecular Biology, 2016
    Co-Authors: Jennifer Duong, Yasunori Tome, Aisada Uchugonova, Yasuyuki Amoh, Norimitsu Saito, Kensei Katsuoka, Fang Liu, Sumiyuki Mii, Robert M. Hoffman
    Abstract:

    Mouse whiskers containing hair-follicle-associated pluripotent (HAP) stem cells, from nestin-driven green fluorescent protein (ND-GFP) transgenic mice, were placed in 3D histoculture supported by Gelfoam(®). β-III tubulin-positive fibers, consisting of ND-GFP-expressing HAP stem cells, extended up to 500 mm from the whisker Nerve Stump in histoculture. The growing fibers had growth cones on their tips expressing F-actin indicating they were growing axons. The growing whisker sensory Nerve was highly enriched in ND-GFP HAP stem cells which appeared to play a major role in its elongation and interaction with other Nerves placed in 3D culture, including the sciatic Nerve, the trigeminal Nerve, and the trigeminal Nerve ganglion. The results suggested that a major function of HAP stem cells in the hair follicle is for growth of the hair follicle sensory Nerve.

  • nestin expressing hair follicle accessible pluripotent stem cells for Nerve and spinal cord repair
    Cells Tissues Organs, 2015
    Co-Authors: Robert M. Hoffman
    Abstract:

    Nestin-expressing stem cells of the hair follicle, discovered by our laboratory, have been shown to be able to form neurons and other nonfollicle cell types. We have shown that the nestin-expressing stem cells from the hair follicle can effect the repair of peripheral Nerve and spinal cord injury. The hair follicle stem cells differentiate into neuronal and glial cells after transplantation to the injured peripheral Nerve and spinal cord, and enhance injury repair and locomotor recovery. We have termed these cells hair follicle-accessible pluripotent (HAP) stem cells. When the excised hair follicle with its Nerve Stump was placed in Gelfoam® 3D histoculture, HAP stem cells grew and extended the hair follicle Nerve which consisted of βIII-tubulin-positive fibers with F-actin expression at the tip. These findings indicate that βIII-tubulin-positive fibers elongating from the whisker follicle sensory Nerve Stump were growing axons. The growing whisker sensory Nerve was highly enriched in HAP stem cells, which appeared to play a major role in its elongation and interaction with other Nerves in 3D Gelfoam® histoculture, including the sciatic Nerve, the trigeminal Nerve, and the trigeminal Nerve ganglion. Our results suggest that a major function of the HAP stem cells in the hair follicle is for growth of the follicle sensory Nerve. HAP stem cells have critical advantages over embryonic stem cells and induced pluripotent stem cells in that they are highly accessible, require no genetic manipulation, are nontumorigenic, and do not present ethical issues for regenerative medicine.

  • nestin expressing stem cells from the hair follicle can differentiate into motor neurons and reduce muscle atrophy after transplantation to injured Nerves
    Tissue Engineering Part A, 2013
    Co-Authors: Fang Liu, Chuansen Zhang, Robert M. Hoffman
    Abstract:

    We have previously shown that nestin-expressing hair follicle stem cells from the mouse and human are multipotent and can differentiate into many cell types, including neurons and glial cells. The nestin-expressing hair follicle stem cells can effect Nerve and spinal cord repair upon transplantation in mouse models. In the present study, nestin-expressing hair follicle stem cells expressing red fluorescent protein (RFP) were induced by retinoic acid and fetal bovine serum to differentiate and then transplanted together with Matrigel into the transected distal sciatic or tibial Nerve Stump of transgenic nude mice ubiquitously expressing green fluorescent protein (GFP). Control mice were transplanted with Matrigel only. The transplanted cells appeared neuron like, with large round nuclei and long extensions. Immunofluorescence staining showed that some of the transplanted cells in the distal Nerve Stump expressed the neuron marker Tuj1 as well as motor neuron markers Isl 1/2 and EN1. These transplanted cell...

  • the role of hair follicle nestin expressing stem cells during whisker sensory Nerve growth in long term 3d culture
    Journal of Cellular Biochemistry, 2013
    Co-Authors: Jennifer Duong, Yasunori Tome, Aisada Uchugonova, Yasuyuki Amoh, Norimitsu Saito, Kensei Katsuoka, Robert M. Hoffman
    Abstract:

    : We have previously reported that nestin-expressing hair follicle stem cells can differentiate into neurons, Schwann cells, and other cell types. In the present study, vibrissa hair follicles, including their sensory Nerve Stump, were excised from transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP mice), and were placed in 3D histoculture supported by Gelfoam®. β-III tubulin-positive fibers, consisting of ND-GFP-expressing cells, extended up to 500 µm from the whisker Nerve Stump in histoculture. The growing fibers had growth cones on their tips expressing F-actin. These findings indicate that β-III tubulin-positive fibers elongating from the whisker follicle sensory Nerve Stump were growing axons. The growing whisker sensory Nerve was highly enriched in ND-GFP cells which appeared to play a major role in its elongation and interaction with other Nerves in 3D culture, including the sciatic Nerve, the trigeminal Nerve, and the trigeminal Nerve ganglion. The results of the present report suggest a major function of the nestin-expressing stem cells in the hair follicle is for growth of the follicle sensory Nerve.

Tessa Gordon - One of the best experts on this subject based on the ideXlab platform.

  • Nerve regeneration understanding biology and its influence on return of function after Nerve transfers
    Hand Clinics, 2016
    Co-Authors: Tessa Gordon
    Abstract:

    Poor functional outcomes are frequent after peripheral Nerve injuries despite the regenerative support of Schwann cells. Motoneurons and, to a lesser extent, sensory neurons survive the injuries but outgrowth of axons across the injury site is slow. The neuronal regenerative capacity and the support of regenerating axons by the chronically denervated Schwann cells progressively declines with time and distance of the injury from the denervated targets. Strategies, including brief low-frequency electrical stimulation that accelerates target reinnervation and functional recovery, and the insertion of cross-bridges between a donor Nerve and a recipient denervated Nerve Stump, are effective in promoting functional outcomes after complete and incomplete injuries.

  • rolipram induced elevation of camp or chondroitinase abc breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral Nerve regeneration
    Experimental Neurology, 2010
    Co-Authors: Esther Udina, Adil Ladak, Matthew J Furey, Thomas M Brushart, Neil Tyreman, Tessa Gordon
    Abstract:

    The inhibitory growth environment of myelin and extracellular matrix proteoglycans in the central nervous system may be overcome by elevating neuronal cAMP or degrading inhibitory proteoglycans with chondroitinase ABC (ChABC). In this study, we asked whether similar mechanisms operate in peripheral Nerve regeneration where effective Wallerian degeneration removes myelin and extracellular proteoglycans slowly. We repaired transected common peroneal (CP) Nerve in rats and either elevated cAMP in the axotomized neurons by subcutaneous rolipram, a specific inhibitor of phosphodiesterase IV, and/or promoted degradation of proteoglycans in the distal Nerve Stump by local ChABC administration. Rolipram treatment significantly increased the number of motoneurons that regenerated axons across the repair site at 1 and 2 weeks, and increased the number of sensory neurons that regenerated axons across the repair site at 2 weeks. Local application of ChABC had a similar effect to rolipram treatment in promoting motor axon regeneration, the effect being no greater when rolipram and ChABC were administered simultaneously. We conclude that blocking inhibitors of axon regeneration by elevating cAMP or degrading proteoglycans in the distal Nerve Stump promotes peripheral axon regeneration after surgical repair of a transected Nerve. It is likely that elevated cAMP is sufficient to encourage axon outgrowth despite the inhibitory growth environment such that simultaneous enzymatic proteoglycan degradation does not promote more axon regeneration than either elevated cAMP or proteoglycan degradation alone.

  • the role of neurotrophic factors in Nerve regeneration
    Neurosurgical Focus, 2009
    Co-Authors: Tessa Gordon
    Abstract:

    This review considers the 2 sources of neurotrophic factors in the peripheral nervous system (PNS), the neurons and the nonneuronal cells in the denervated distal Nerve Stumps, and their role in axon regeneration. Morphological assessment of regenerative success in response to administration of exogenous growth factors after Nerve injury and repair has indicated a role of the endogenous neurotrophic factors from Schwann cells in the distal Nerve Stump. However, the increased number of axons may reflect more neurons regenerating their axons and/or increased numbers of axon sprouts from the same number of neurons. Using fluorescent dyes to count neurons that regenerated their axons across a suture site and into distal Nerve Stumps, brain-derived neurotrophic factor (BDNF) and glial cell–derived neurotrophic factor (GDNF) were found not to increase the number of neurons that regenerated their axons after immediate Nerve repair. Nevertheless, the factors did reverse the deleterious effect of delayed Nerve rep...

  • glial cell line derived neurotrophic factor and brain derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo
    Experimental Neurology, 2003
    Co-Authors: J G Boyd, Tessa Gordon
    Abstract:

    In contrast to injuries in the central nervous system, injured peripheral neurons will regenerate their axons. However, axotomized motoneurons progressively lose their ability to regenerate their axons, following peripheral Nerve injury often resulting in very poor recovery of motor function. A decline in neurotrophic support may be partially responsible for this effect. The initial upregulation of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) by Schwann cells of the distal Nerve Stump after Nerve injury has led to the speculation that they are important for motor axonal regeneration. However, few experiments directly measure the effects of exogenous BDNF or GDNF on motor axonal regeneration. This study provided the first direct and quantitative evidence that long-term continuous treatment with exogenous GDNF significantly increased the number of motoneurons which regenerate their axons, completely reversing the negative effects of chronic axotomy. The beneficial effect of GDNF was not dose-dependent. A combination of exogenous GDNF and BDNF on motor axonal regeneration was significantly greater than either factor alone, and this effect was most pronounced following long-term continuous treatment. The ability of GDNF, either alone or in combination with BDNF, to increase the number of motoneurons that regenerated their axons correlated well with an increase in axon sprouting within the distal Nerve Stump. Thus long-term continuous treatment with neurotrophic factors, such as GDNF and BDNF, can be used as a viable treatment to sustain motor axon regeneration.

  • chronic schwann cell denervation and the presence of a sensory Nerve reduce motor axonal regeneration
    Experimental Neurology, 2002
    Co-Authors: Olawale A R Sulaiman, Rajiv Midha, Catherine A Munro, Takeshi Matsuyama, Abdulhakeem A Almajed, Tessa Gordon
    Abstract:

    Motor axonal regeneration is compromised by chronic distal Nerve Stump denervation, induced by delayed repair or prolonged regeneration distance, suggesting that the pathway for regeneration is progressively impaired with time and/or distance. In the present experiments, we tested the impacts of (i) chronic distal sensory Nerve Stump denervation on axonal regeneration and (ii) sensory or motor innervation of a Nerve graft on the ability of motoneurons to regenerate their axons from the opposite end of the graft. Using the motor and sensory branches of rat femoral Nerve and application of neuroanatomical tracers, we evaluated the numbers of regenerated femoral motoneurons and Nerve fibers when motoneurons regenerated (i) into freshly cut and 2-month chronically denervated distal sensory Nerve Stump, (ii) alone into a 4-cm-long distally ligated sensory autograft (MGL) and, (iii) concurrently as sensory (MGS) or motor (MGM) Nerves regenerated into the same autograft from the opposite end. We found that all (315 ± 24: mean ± SE) the femoral motoneurons regenerated into a freshly cut distal sensory Nerve Stump as compared to 254 ± 20 after 2 months of chronic denervation. Under the MGL condition, 151 ± 5 motoneurons regenerated, which was not significantly different from the MGM group (134 ± 13) but was significantly reduced to 99 ± 2 in the MGS group (P < 0.05). The number of regenerated Nerve fibers was 1522 ± 81 in the MGL group, 888 ± 18 in the MGM group, and 516 ± 44 in the MGS group, although the high number of Nerve fibers in the MGL group was due partly to the elaboration of multiple sprouts. Nerve fiber number and myelination were reduced in the MGS group and increased in the MGM group. These results demonstrate that both chronic denervation and the presence of sensory Nerve axons reduced desired motor axonal regeneration into sensory pathways. A common mechanism may involve reduced responsiveness of sensory Schwann cells within the Nerve graft or chronically denervated distal Nerve Stump to regenerating motor axons. The findings confirm that motor regeneration is optimized by avoiding even short-term denervation. They also imply that repairing pure motor Nerves (without their cutaneous sensory components) to distal Nerve Stumps should be considered clinically when motor recovery is the main desired outcome.

Xinpeng Dun - One of the best experts on this subject based on the ideXlab platform.

  • distinct vip and pacap functions in the distal Nerve Stump during peripheral Nerve regeneration
    Frontiers in Neuroscience, 2019
    Co-Authors: Patricia K Woodley, Qing Min, Nina F Mulvey, David Parkinson, Xinpeng Dun
    Abstract:

    Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylyl Cyclase Activating Peptide (PACAP) are regeneration-associated neuropeptides, which are up-regulated by neurons following peripheral Nerve injury. So far, they have only been studied for their roles as autocrine signals for both neuronal survival and axon outgrowth during peripheral Nerve regeneration. In this report, we examined VIP and PACAP's paracrine effects on Schwann cells and macrophages in the distal Nerve Stump during peripheral Nerve regeneration. We show that VPAC1, VPAC2, and PAC1 are all up-regulated in the mouse distal Nerve following peripheral Nerve injury and are highly expressed in Schwann cells and macrophages within the distal sciatic Nerve. We further investigated the effect of VIP and PACAP on cultured rat Schwann cells, and found that VIP and PACAP can not only promote myelin gene expression in Schwann cells but can also inhibit the release of pro-inflammatory cytokines by Schwann cells. Furthermore, we show that VIP and PACAP inhibit the release of pro-inflammatory cytokines and enhance anti-inflammatory cytokine expression in sciatic Nerve explants. Our results provide evidence that VIP and PACAP could have important functions in the distal Nerve Stump following injury to promote remyelination and regulate the inflammatory response. Thus, VIP and PACAP receptors appear as important targets to promote peripheral Nerve repair following injury.

  • analysis of schwann cell migration and axon regeneration following Nerve injury in the sciatic Nerve bridge
    Frontiers in Molecular Neuroscience, 2019
    Co-Authors: Bing Chen, Quan Chen, David B Parkinson, Xinpeng Dun
    Abstract:

    While it is proposed that interaction between Schwann cells and axons is key for successful Nerve regeneration, the behavior of Schwann cells migrating into a Nerve gap following a transection injury and how migrating Schwann cells interact with regenerating axons within the Nerve bridge has not been studied in detail. In this study, we combine the use of our whole-mount sciatic Nerve staining with the use of a proteolipid protein-green fluorescent protein (PLP-GFP) mouse model to mark Schwann cells and have examined the behavior of migrating Schwann cells and regenerating axons in the sciatic Nerve gap following a Nerve transection injury. We show here that Schwann cell migration from both Nerve Stumps starts later than the regrowth of axons from the proximal Nerve Stump. The first migrating Schwann cells are only observed 4 days following mouse sciatic Nerve transection injury. Schwann cells migrating from the proximal Nerve Stump overtake regenerating axons on day 5 and form Schwann cell cords within the Nerve bridge by 7 days post-transection injury. Regenerating axons begin to attach to migrating Schwann cells on day 6 and then follow their trajectory navigating across the Nerve gap. We also observe that Schwann cell cords in the Nerve bridge are not wide enough to guide all the regenerating axons across the Nerve bridge, resulting in regenerating axons growing along the outside of both proximal and distal Nerve Stumps. From this analysis, we demonstrate that Schwann cells play a crucial role in controlling the directionality and speed of axon regeneration across the Nerve gap. We also demonstrate that the use of the PLP-GFP mouse model labeling Schwann cells together with the whole sciatic Nerve axon staining technique is a useful research model to study the process of peripheral Nerve regeneration.

  • macrophage derived slit3 controls cell migration and axon pathfinding in the peripheral Nerve bridge
    Cell Reports, 2019
    Co-Authors: Patricia K Woodley, Xinpeng Dun, Lauren Carr, Riordan W Barry, Louisa K Drake, Thomas Mindos, Sheridan L Roberts, Alison C Lloyd
    Abstract:

    Summary Slit-Robo signaling has been characterized as a repulsive signal for precise axon pathfinding and cell migration during embryonic development. Here, we describe a role for Sox2 in the regulation of Robo1 in Schwann cells and for Slit3-Robo1 signaling in controlling axon guidance within the newly formed Nerve bridge following peripheral Nerve transection injury. In particular, we show that macrophages form the outermost layer of the Nerve bridge and secrete high levels of Slit3, while migratory Schwann cells and fibroblasts inside the Nerve bridge express the Robo1 receptor. In line with this pattern of Slit3 and Robo1 expression, we observed multiple axon regeneration and cell migration defects in the Nerve bridge of Sox2-, Slit3-, and Robo1-mutant mice. Our findings have revealed important functions for macrophages in the peripheral nervous system, utilizing Slit3-Robo1 signaling to control correct peripheral Nerve bridge formation and precise axon targeting to the distal Nerve Stump following injury.

L. Stejskal - One of the best experts on this subject based on the ideXlab platform.

  • Reinnervation of the rat musculocutaneous Nerve Stump after its direct reconnection with the C5 spinal cord segment by the Nerve graft following avulsion of the ventral spinal roots: a comparison of intrathecal administration of brain-derived neurotr
    Experimental Brain Research, 2004
    Co-Authors: P. Haninec, P. Dubový, F. Šámal, L. Houštava, L. Stejskal
    Abstract:

    Experimental model based on the C5 ventral root avulsion was used to evaluate the efficacy of brain-derived neurotrophic factor (BDNF) and Cerebrolysin treatment on motor neuron maintenance and survival resulted in the functional reinnervation of the Nerve Stump. In contrast to vehicle, BDNF treatment reduced the loss and atrophy of motor neurons and enhanced the regrowth axon sprouts into the distal Stump of musculocutaneous Nerve. However, the axon diameter of the myelinated fibers was smaller than those of control rats. The morphometric results were related to a low score in behavioral test similar to vehicle-treated rats. Cerebrolysin treatment greatly protected the motor neurons against cell death. Moreover, morphometric features of myelinated axons were better than those of rats treated with vehicle or BDNF. The mean score of grooming test suggested better results of the functional motor reinnervation than after BDNF administration. The majority of rescued motor neurons regenerating their axons through Nerve graft in both BDNF- and Cerebrolysin-treated rats expressed choline acetyltransferase immunostaining. The results demonstrate that BDNF has more modest effects in preventing the death of motor neurons and functional recovery of injured motor Nerve after root avulsion than Cerebrolysin.

  • reinnervation of the rat musculocutaneous Nerve Stump after itsdirect reconnection with the c5 spinal cord segment
    Experimental Brain Research, 2004
    Co-Authors: P. Haninec, P. Dubový, F. Šámal, Ladislav Housťava, L. Stejskal
    Abstract:

    Experimental model based on the C5 ventral root avulsion was used to evaluate the efficacy of brainderived neurotrophic factor (BDNF) and Cerebrolysin treatment on motor neuron maintenance and survival resulted in the functional reinnervation of the Nerve Stump. In contrast to vehicle, BDNF treatment reduced the loss and atrophy of motor neurons and enhanced the regrowth axon sprouts into the distal Stump of musculocutaneous Nerve. However, the axon diameter of the myelinated fibers was smaller than those of control rats. The morphometric results were related to a low score in behavioral test similar to vehicle-treated rats. Cerebrolysin treatment greatly protected the motor neurons against cell death. Moreover, morphometric features of myelinated axons were better than those of rats treated with vehicle or BDNF. The mean score of grooming test suggested better results of the functional motor reinnervation than after BDNF administration. The majority of rescued motor neurons regenerating their axons through Nerve graft in both BDNF- and Cerebrolysin-treated rats expressed choline acetyltransferase immunostaining. The results demonstrate that BDNF has more modest effects in preventing the death of motor neurons and functional recovery of injured motor Nerve after root avulsion than Cerebrolysin.

  • acellular Nerve graft re seeded by schwann cells migrating from the Nerve Stump can stimulate spinal motoneurons for functional reinnervation of the rat muscle
    Annals of Anatomy-anatomischer Anzeiger, 2000
    Co-Authors: P. Haninec, P. Dubový, L. Houštava, L. Stejskal
    Abstract:

    Summary The acellular Nerve graft was utilised to restore a functional reinnervation of the biceps brachii muscle from the motoneuron pool of the cervical spinal cord. The musculocutaneous Nerve Stump was sutured to an acellular Nerve graft, the opposite end of which was inserted into the cervical spinal cord cranial to the avulsed C5 ventral root. The acellular Nerve graft was repopulated by Schwann cells heavily immunostained for NGFr within 90 days. The Schwann cells migrating from the Nerve Stump reached the spinal cord grey matter, where they stimulated the motoneurons to send axonal sprouts. The functional reinnervation of the biceps brachii muscle was assessed by means of the behavioural (grooming) test and EMG, the presence of myelinated and unmyelinated axons was demonstrated by light and electron microscopy. The axonal reconnection of the musculocutaneous Nerve Stump was verified by horseradish peroxidase retrograde labelling of the spinal motoneurons. Moreover, the motoneurons on the operated side of the C5 spinal segment displayed increased immunostaining for GAP-43 in comparison to the contralateral side, whereas the pattern of AChE histochemical reaction was similar on both the operated and contralateral side, of the C5 segment 150 days after acellular graft implantation. The regenerated axons bridged a 4-cm long originally acellular Nerve graft to reach and reinnervate the biceps brachii muscle. The reinnervation of the neuromuscular junctions was morphologically determined by immunofluorescence for neurofilaments. The number of myelinated axons in the acellular Nerve graft was significantly higher than those growing over the cellular graft, but their diameter was smaller. The results of experiments presented here demonstrate functional recovery of the biceps muscle reinnervation through the acellular Nerve graft repopulated by migrating Schwann cells. The process of reinnervation by acellular Nerve graft is however delayed and worse in comparison with the cellular graft.

Margaret Fahnestock - One of the best experts on this subject based on the ideXlab platform.

  • Long-term changes in neurotrophic factor expression in distal Nerve Stump following denervation and reinnervation with motor or sensory Nerve
    Journal of neurochemistry, 2008
    Co-Authors: Bernadeta Michalski, James R. Bain, Margaret Fahnestock
    Abstract:

    Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor Nerve Stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal Nerve neurotrophic factor expression. We found that transected distal tibial Nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neurotrophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal Nerve Stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory Nerve (the cutaneous saphenous Nerve) sutured to distal tibial Nerve lowered injury-induced BDNF and GDNF mRNA levels in distal Stump, but repair with a mixed Nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed Nerves did not affect Nerve growth factor or neurotrophin-3 expression. Thus, distal Nerve contributed to a neurotrophic environment for Nerve regeneration for at least 6 months, and sensory Nerve repair helped normalize distal Nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal Stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory Nerve.

  • improved functional recovery of denervated skeletal muscle after temporary sensory Nerve innervation
    Neuroscience, 2001
    Co-Authors: James R. Bain, Karen Veltri, D Chamberlain, Margaret Fahnestock
    Abstract:

    Prolonged muscle denervation results in poor functional recovery after Nerve repair. The possible protective effect of temporary sensory innervation of denervated muscle, prior to motor Nerve repair, has been examined in the rat. Soleus and gastrocnemius muscles were denervated by cutting the tibial Nerve, and the peroneal Nerve was then sutured to the transected distal tibial Nerve Stump either immediately or after two, four or six months. In half of the animals with delayed repair, the saphenous (sensory) Nerve was temporarily attached to the distal Nerve Stump. Muscles were evaluated three months after the peroneal-to-tibial union, and were compared with each other, with unoperated control muscles and with untreated denervated muscles. After four to six months of sensory "protection", gastrocnemius muscles weighed significantly more than unprotected muscles, and both gastrocnemius and soleus muscles exhibited better preservation of their structure, with less fiber atrophy and connective tissue hyperplasia. The maximum compound action potentials were significantly larger in gastrocnemius and soleus muscles following sensory protection, irrespective of the delay in motor Nerve union. Isometric force, although less than in control animals and in those with immediate Nerve repair, remained reasonably constant after sensory protection, while in unprotected muscles there was a progressive and significant decline as the period of denervation lengthened. We interpret these results as showing that, although incapable of forming excitable neuromuscular junctions, sensory Nerves can nevertheless exert powerful trophic effects on denervated muscle fibers. We propose that these findings indicate a useful strategy for improving the outcome of peripheral Nerve surgery.