Ayato Hayashi

Juntendo University, Tokyo, Tokyo-to, Japan

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Publications (19)46.48 Total impact

  • Article: Hemihypoglossal nerve transfer for acute facial paralysis.
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    ABSTRACT: Object The authors have developed a technique for the treatment of facial paralysis that utilizes anastomosis of the split hypoglossal and facial nerve. Here, they document improvements in the procedure and experimental evidence supporting the approach. Methods They analyzed outcomes in 36 patients who underwent the procedure, all of whom had suffered from facial paralysis following the removal of large vestibular schwannomas. The average period of paralysis was 6.2 months. The authors used 5 different variations of a procedure for selecting the split nerve, including evaluation of the split nerve using recordings of evoked potentials in the tongue. Results Successful facial reanimation was achieved in 16 of 17 patients using the cephalad side of the split hypoglossal nerve and in 15 of 15 patients using the caudal side. The single unsuccessful case using the cephalad side of the split nerve resulted from severe infection of the cheek. Procedures using the ansa cervicalis branch yielded poor success rates (2 of 4 cases). Some tongue atrophy was observed in all variants of the procedure, with 17 cases of minimal atrophy and 14 cases of moderate atrophy. No procedure led to severe atrophy causing functional deficits of the tongue. Conclusions The split hypoglossal-facial nerve anastomosis procedure consistently leads to good facial reanimation, and the use of either half of the split hypoglossal nerve results in facial reanimation and moderate tongue atrophy.
    Journal of Neurosurgery 10/2012; · 2.96 Impact Factor
  • Article: The medial plantar flap vascularized by the reverse flow lateral plantar artery: a novel variation through the case of aggressive digital papillary adenocarcinoma of the sole.
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    ABSTRACT: Aggressive digital papillary adenocarcinoma (ADPA) is a rare neoplasm of eccrine sweat gland origin that typically presents as a mass on the distal extremities. It is associated with high rates of local recurrence and distal metastasis. Presented here is the case of a 61-year-old male who developed ADPA on his distal sole just above the head of the first metatarsal bone. Wide excision of the tumor involving a 3-cm skin margin from previous surgical scar of biopsy was performed, and sentinel lymph node biopsies were taken from the popliteal fossa and inguinal regions. During this wide excision surgery, the pedicle for the reverse medial plantar flap had to be removed along with the tumor. Reconstructive surgery was performed with a medial plantar flap that was vascularized with a lateral plantar artery in a reverse fashion. This flap successfully covered the defect and the patient can walk without any problems. However, the pedicle crossed the donor site somewhat tightly and the flap became congested for a while. Therefore, it is important to ensure careful handling of the donor site when performing this procedure.
    Journal of Reconstructive Microsurgery 06/2012; 28(6):427-30. · 1.43 Impact Factor
  • Article: "Sea anemone-shaped fixation": a feasible tie-over technique for axillary osmidrosis.
    Journal of Plastic Reconstructive & Aesthetic Surgery 02/2012; 65(7):e202-3. · 1.49 Impact Factor
  • Article: Multiple rheumatoid bursal cysts that were finally effectively treated by combining surgical resection and sclerotherapy.
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    ABSTRACT: A 71-year-old male who had been diagnosed with rheumatoid arthritis 3 years previously developed multiple subcutaneous cysts on his buttock, elbow, knee, hand and back. The diameters of the cysts were 10-15 cm. The characteristic fluid and pathology of the cysts led to the diagnosis of multiple rheumatoid bursal cyst (MRBC). The patient was keen to treat the cyst on his buttock as it hampered his sitting position. However, it resisted several kinds of sclerotherapies, including absolute alcohol, OK-432, minocycline and dexamethasone. When the cyst grew further, it was resected surgically; however, the cyst recurred immediately. It was finally brought under control by injecting it with OK-432. The thick cyst wall, which resisted the various sclerotherapies, was removed surgically, and a new capsule developed inside the cavity; adding a sclerotant to newly made thin capsule made us possible to treat this resistant large bursal cyst.
    Journal of Plastic Reconstructive & Aesthetic Surgery 09/2011; 65(2):e29-32. · 1.49 Impact Factor
  • Article: The supernumerary nostril.
    Takashi Matsumura, Ayato Hayashi, Yuzo Komuro
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    ABSTRACT: The supernumerary nostril is a very rare congenital nasal abnormality, and several cases have been reported in the literature since 1906 when the first case was reported by Lindsay. In the other previously reported cases, the supernumerary nostril typically could present unilaterally or bilaterally, and it was therefore called a double nose, with most reported cases being unilateral. At our institution, we encountered a patient with a supernumerary nostril that was located above the left nostril. We thus performed an operation on this supernumerary nostril and obtained good results and a successful postoperative course. We herein present our findings while also discussing the pertinent literature.
    The Journal of craniofacial surgery 05/2010; 21(3):808-10. · 0.81 Impact Factor
  • Article: The differential effects of pathway- versus target-derived glial cell line-derived neurotrophic factor on peripheral nerve regeneration.
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    ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) has potent survival effects on central and peripheral nerve populations. The authors examined the differential effects of GDNF following either a sciatic nerve crush injury in mice that overexpressed GDNF in the central or peripheral nervous systems (glial fibrillary acidic protein [GFAP]-GDNF) or in the muscle target (Myo-GDNF). Adult mice (GFAP-GDNF, Myo-GDNF, or wild-type [WT] animals) underwent sciatic nerve crush and were evaluated using histomorphometry and muscle force and power testing. Uninjured WT animals served as controls. In the sciatic nerve crush, the Myo-GDNF mice demonstrated a higher number of nerve fibers, fiber density, and nerve percentage (p < 0.05) at 2 weeks. The early regenerative response did not result in superlative functional recovery. At 3 weeks, GFAP-GDNF animals exhibit fewer nerve fibers, decreased fiber width, and decreased nerve percentage compared with WT and Myo-GDNF mice (p < 0.05). By 6 weeks, there were no significant differences between groups. Peripheral delivery of GDNF resulted in earlier regeneration following sciatic nerve crush injuries than that with central GDNF delivery. Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury.
    Journal of Neurosurgery 11/2009; 113(1):102-9. · 2.96 Impact Factor
  • Article: Axotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy.
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    ABSTRACT: End-to-side (ETS) nerve repair remains an area of intense scrutiny for peripheral nerve surgeon-scientists. In this technique, the transected end of an injured nerve, representing the "recipient" is sutured to the side of an uninjured "donor" nerve. Some works suggest that the recipient limb is repopulated with regenerating collateral axonal sprouts from the donor nerve that go on to form functional synapses. Significant, unresolved questions include whether the donor nerve needs to be injured to facilitate regeneration, and whether a single donor neuron is capable of projecting additional axons capable of differentially innervating disparate targets. We serially imaged living transgenic mice (n=66) expressing spectral variants of GFP in various neuronal subsets after undergoing previously described atraumatic, compressive, or epineurotomy forms of ETS repair (n=22 per group). To evaluate the source, and target innervation of these regenerating axons, nerve morphometry and retrograde labeling were further supplemented by confocal microscopy as well as Western blot analysis. Either compression or epineurotomy with inevitable axotomy were required to facilitate axonal regeneration into the recipient limb. Progressively more injurious models were associated with improved recipient nerve reinnervation (epineurotomy: 184+/-57.6 myelinated axons; compression: 78.9+/-13.8; atraumatic: 0), increased Schwann cell proliferation (epineurotomy: 72.2% increase; compression: 39% increase) and cAMP response-element binding protein expression at the expense of a net deficit in donor axon counts distal to the repair. These differences were manifest by 150 days, at which point quantitative evidence for pruning was obtained. We conclude that ETS repair relies upon injury to the donor nerve.
    Experimental Neurology 07/2008; 211(2):539-50. · 4.70 Impact Factor
  • Article: The impact of motor and sensory nerve architecture on nerve regeneration.
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    ABSTRACT: Sensory nerve autografting is the standard of care for injuries resulting in a nerve gap. Recent work demonstrates superior regeneration with motor nerve grafts. Improved regeneration with motor grafting may be a result of the nerve's Schwann cell basal lamina tube size. Motor nerves have larger SC basal lamina tubes, which may allow more nerve fibers to cross a nerve graft repair. Architecture may partially explain the suboptimal clinical results seen with sensory nerve grafting techniques. To define the role of nerve architecture, we evaluated regeneration through acellular motor and sensory nerve grafts. Thirty-six Lewis rats underwent tibial nerve repairs with 5 mm double-cable motor or triple-cable sensory nerve isografts. Grafts were harvested and acellularized in University of Wisconsin solution. Control animals received fresh motor or sensory cable isografts. Nerves were harvested after 4 weeks and histomorphometry was performed. In 6 animals per group from the fresh motor and sensory cable graft groups, weekly walking tracks and wet muscle mass ratios were performed at 7 weeks. Histomorphometry revealed more robust nerve regeneration in both acellular and cellular motor grafts. Sensory groups showed poor regeneration with significantly decreased percent nerve, fiber count, and density (p<0.05). Walking tracks revealed a trend toward improved functional recovery in the motor group. Gastrocnemius wet muscle mass ratios show a significantly greater muscle mass recovery in the motor group (p<0.05). Nerve architecture (size of SC basal lamina tubes) plays an important role in nerve regeneration in a mixed nerve gap model.
    Experimental Neurology 04/2008; 212(2):370-6. · 4.70 Impact Factor
  • Article: Induction of regional collateral sprouting following muscle denervation.
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    ABSTRACT: Anecdotal clinical findings suggest that denervated muscle may regain modest functional recovery via spontaneous collateral sprouts from intact adjacent nerve fibers. The current study evaluates the conditions needed for the denervated masseter muscle to induce axonal sprouting from the facial nerve. We hypothesize that epineurial injury is required to induce collateral sprouting toward a neighboring denervated muscle. Twelve thy1-yellow fluorescent protein-16 (thy1-YFP-16) transgenic mice whose axons express yellow fluorescent protein were allocated into six groups, with four degrees of facial nerve injury (intact, crush, transection, removed segment) with or without masseter denervation. Animals underwent serial in vivo imaging analyses under the fluorescent microscope weekly for 5 or 7 weeks and were subsequently perfused for analysis. Masseter muscle acetylcholine receptors (AChRs) were stained with Alexa Fluor 594 conjugated alpha-bungarotoxin, and whole mounts were imaged with confocal microscopy. In groups with intact or crushed facial nerves, no evidence of collateral sprouting was demonstrated. Mice with transected facial nerve branches or removed segments demonstrated sprouting from the proximal stump into the denervated masseter. Staining of the AChRs confirmed that new neuromuscular junctions were established between the facial nerve and the denervated masseter. This study suggests that epineurial injury is required to stimulate axonal sprouting into adjacent denervated muscle. Nerves with compromised epineurium may be useful in promoting neo-neurotization after muscle denervation.
    The Laryngoscope 11/2007; 117(10):1735-40. · 1.75 Impact Factor
  • Article: Retrograde labeling in peripheral nerve research: it is not all black and white.
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    ABSTRACT: Retrograde labeling has become an important method of evaluation for peripheral nerve regeneration after injury. We review the features of the commonly used retrograde tracers Fast Blue, Fluoro-Gold, and Fluoro Ruby in addition to the various application methods (conduit reservoir, intramuscular injection, and crystal powder application) and the techniques used to count stained neurons. Upon application of the staining techniques and dyes in a rat and mouse nerve injury model, Fluoro-Gold was found to stain the greatest number of neurons with all application methods. However, due to variability of staining intensity, neuron size, and background staining, it is difficult to count the stained neurons accurately. Fast Blue stains consistently using intramuscular injection in the mouse but fails to provide adequate staining using the muscle injection method in the rat model and shows high failure rates using the conduit reservoir technique. However, crystal dye application with Fast Blue to the cut nerve end provides excellent results. We believe that it is imperative to use the various tracers and application methods prior to their experimental use to develop a consistent standardized approach to retrograde labeling.
    Journal of Reconstructive Microsurgery 11/2007; 23(7):381-9. · 1.43 Impact Factor
  • Article: A double-transgenic mouse used to track migrating Schwann cells and regenerating axons following engraftment of injured nerves.
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    ABSTRACT: We propose that double-transgenic thy1-CFP(23)/S100-GFP mice whose Schwann cells constitutively express green fluorescent protein (GFP) and axons express cyan fluorescent protein (CFP) can be used to serially evaluate the temporal relationship between nerve regeneration and Schwann cell migration through acellular nerve grafts. Thy1-CFP(23)/S100-GFP and S100-GFP mice received non-fluorescing cold preserved nerve allografts from immunologically disparate donors. In vivo fluorescent imaging of these grafts was then performed at multiple points. The transected sciatic nerve was reconstructed with a 1-cm nerve allograft harvested from a Balb-C mouse and acellularized via 7 weeks of cold preservation prior to transplantation. The presence of regenerated axons and migrating Schwann cells was confirmed with confocal and electron microscopy on fixed tissue. Schwann cells migrated into the acellular graft (163+/-15 intensity units) from both proximal and distal stumps, and bridged the whole graft within 10 days (388+/-107 intensity units in the central 4-6 mm segment). Nerve regeneration lagged behind Schwann cell migration with 5 or 6 axons imaged traversing the proximal 4 mm of the graft under confocal microcopy within 10 days, and up to 21 labeled axons crossing the distal coaptation site by 15 days. Corroborative electron and light microscopy 5 mm into the graft demonstrated relatively narrow diameter myelinated (431+/-31) and unmyelinated (64+/-9) axons by 28 but not 10 days. Live imaging of the double-transgenic thy1-CFP(23)/S100-GFP murine line enabled serial assessment of Schwann cell-axonal relationships in traumatic nerve injuries reconstructed with acellular nerve allografts.
    Experimental Neurology 10/2007; 207(1):128-38. · 4.70 Impact Factor
  • Article: Reinnervation of the tibialis anterior following sciatic nerve crush injury: a confocal microscopic study in transgenic mice.
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    ABSTRACT: Transgenic mice whose axons and Schwann cells express fluorescent chromophores enable new imaging techniques and augment concepts in developmental neurobiology. The utility of these tools in the study of traumatic nerve injury depends on employing nerve models that are amenable to microsurgical manipulation and gauging functional recovery. Motor recovery from sciatic nerve crush injury is studied here by evaluating motor endplates of the tibialis anterior muscle, which is innervated by the deep peroneal branch of the sciatic nerve. Following sciatic nerve crush, the deep surface of the tibialis anterior muscle is examined using whole mount confocal microscopy, and reinnervation is characterized by imaging fluorescent axons or Schwann cells (SCs). One week following sciatic crush injury, 100% of motor endplates are denervated with partial reinnervation at 2 weeks, hyperinnervation at 3 and 4 weeks, and restoration of a 1:1 axon to motor endplate relationship 6 weeks after injury. Walking track analysis reveals progressive recovery of sciatic nerve function by 6 weeks. SCs reveal reduced S100 expression within 2 weeks of denervation, correlating with regression to a more immature phenotype. Reinnervation of SCs restores S100 expression and a fully differentiated phenotype. Following denervation, there is altered morphology of circumscribed terminal Schwann cells demonstrating extensive process formation between adjacent motor endplates. The thin, uniformly innervated tibialis anterior muscle is well suited for studying motor reinnervation following sciatic nerve injury. Confocal microscopy may be performed coincident with other techniques of assessing nerve regeneration and functional recovery.
    Experimental Neurology 10/2007; 207(1):64-74. · 4.70 Impact Factor
  • Article: End-to-side nerve repair: review of the literature.
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    ABSTRACT: End-to-side (ETS) nerve repair, in which the distal stump of a transected nerve is coapted to the side of an uninjured donor nerve, offers a technique for repair of peripheral nerve injuries where the proximal nerve stump is unavailable or a significant nerve gap exists. Details of animal models are explored including motor and sensory regeneration to further clarify the mechanism of collateral sprouting while eliminating false positive results from contaminating axons. Some experimental studies support the conclusion that sensory or motor reinnervation may be derived from collateral sprouting while others suggest that reinnervation requires an injury to the donor nerve. Clinical experience with ETS neurorrhaphy includes management of upper extremity nerve injury, facial reanimation, reconstruction following tumor ablation, and the prevention of neuroma formation. Our interpretation of the ETS literature suggests that sensory axons may sprout without deliberately attempting to injure them, while motor axons regenerate only in response to a deliberate injury. Experimental and clinical experience with ETS neurorrhaphy has rendered mixed results. Our interpretation of the literature suggests that the success of this technique is dependent upon axonal injury of motor and possibly sensory nerves. While continued clinical and laboratory experimentation with ETS nerve repair is warranted, it should not yet replace more established techniques of nerve repair.
    Restorative neurology and neuroscience 02/2007; 25(1):45-63. · 2.51 Impact Factor
  • Article: Hemi-orbicularis oculi switch flap for upper eyelid defects.
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    ABSTRACT: The technique chosen to reconstruct anterior lamellar defects of the upper eyelid requires careful consideration. We modified pre-existing techniques used to reconstruct anterior lamellar defects after tumour resection and have called this procedure a hemi-orbicularis oculi switch flap. This musculocutaneous flap is elevated with underlying orbicularis and its base abuts the anterior lamellar defect. The flap, which is half the height of the defect, is elevated and inset to cover the defect. Then, taking into consideration the extensibility of upper eyelid skin, the remainder of the defect and the donor site are closed directly. Five patients with basal cell carcinoma, haemangioma, and xanthoma of the upper eyelid were treated by this method. All flaps survived and complications were minimal. Aesthetically and functionally good results were obtained by this method. We have developed a surgical method for the reconstruction of anterior lamellar defects of the upper eyelid. The proposed method is technically simple and safe and provides consistent results for a potentially wide variety of upper eyelid tumours.
    Journal of Plastic Reconstructive & Aesthetic Surgery 02/2007; 60(6):655-8. · 1.49 Impact Factor
  • Article: Repair of motor nerve gaps with sensory nerve inhibits regeneration in rats.
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    ABSTRACT: Sensory nerve grafts are often used to reconstruct injured motor nerves, but the consequences of such motor/sensory mismatches are not well studied. Sensory nerves have more diverse fiber distributions than motor nerves and may possess phenotypically distinct Schwann cells. Putative differences in Schwann cell characteristics and pathway architecture may negatively affect the regeneration of motor neurons down sensory pathways. We hypothesized that sensory grafts impair motor target reinnervation, thereby contributing to suboptimal outcomes. This study investigated the effect of motor versus sensory grafts on nerve regeneration and functional recovery. The authors conducted a prospective, randomized, controlled animal study. Fifty-six Lewis rats were randomized to seven groups of eight animals each. Five-millimeter tibial nerve defects were reconstructed with motor or sensory nerve grafts comprised of single, double, triple, or quadruple cables. Tibial nerve autografts served as positive controls. Three weeks after reconstruction, nerves were harvested for histologic examination and quantitative histomorphometric analysis. Wet muscle masses provided an index of functional recovery. Nerve regeneration was significantly greater across motor versus sensory nerve grafts independent of graft cross-sectional area or cable number. Motor grafts demonstrated increased nerve density, percent nerve, and total fiber number (P < .05). Normalized wet muscle masses trended toward improved recovery in motor versus sensory groups. Reconstruction of tibial nerve defects with nerve grafts of motor versus sensory origin enhanced nerve regeneration independent of cable number in a rodent model. Preferential nerve regeneration through motor nerve grafts may also promote functional recovery with potential implications for clinical nerve reconstruction.
    The Laryngoscope 10/2006; 116(9):1685-92. · 1.75 Impact Factor
  • Article: A New Surgical Technique for Polysyndactyly of the Toes without Skin Graft.
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    ABSTRACT: Reconstruction for polysyndactyly of the toes aims at cosmetic improvement. A previous method that uses a skin graft has inherent disadvantages of mismatched pigmentation between the graft and the surrounding skin and scar formation at the donor site. The authors' new improved surgical technique for the treatment of polysyndactyly of the toes does not require a skin graft and therefore avoids these problems. The authors designed a subcutaneous flap from the distal portion of a rectangular flap of skin from the dorsal side of the interdigital webbing and moved the former flap to the sidewall of the base of a toe. Both flaps are the same size; therefore, an interdigital space had to be of sufficient size to accommodate both of them. To ensure an adequate blood supply to the flap, careful handling of the subcutaneous flap is essential for success. This procedure can apply to polysyndactyly of the fourth, fifth, and sixth toes when the fourth and fifth toes adhere over the distal side of the distal interphalangeal joint and when the skin on the dorsal side of the fifth toe, regarded as the excessive one, is at lease twice the size of the dorsal rectangular flap. Ten patients with polysyndactyly of the toe were treated with this method. Aesthetically good results were obtained.
    Plastic &amp Reconstructive Surgery 09/2004; 114(2):433-8. · 3.38 Impact Factor
  • Article: Treatment of unilateral lambdoid synostosis with cranial distraction.
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    ABSTRACT: The accurate diagnosis and treatment of posterior plagiocephaly have been a source of controversy. The unilateral lambdoid synostosis that is characterized by flattening of ipsilateral occipital bone is a rare type of craniosynostosis. An 8-month-old infant with unilateral lambdoid synostosis is reported. The patient exhibited right occipital flattening, mastoid bulge, and right frontal bone prominence, with the right auricle displaced anteroinferiorly on gross examination. A Towne projection radiograph of the skull and three-dimensional computed tomography scans revealed that the right lambdoid suture was prematurely fused. Correction of the cranial shape was performed using distraction osteogenesis combined with a barrel stave osteotomy. Significant improvement in the skull was observed 1 year after surgery.
    Journal of Craniofacial Surgery 08/2004; 15(4):609-13. · 0.82 Impact Factor
  • Article: Collateral sprouting occurs following end-to-side neurorrhaphy.
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    ABSTRACT: Recent evidence supports the use of end-to-side neurorrhaphy for the treatment of certain peripheral nerve disorders. However, the mechanism by which nerves regenerate following this procedure is still unclear. To address this question, the authors designed a new end-to-side coaptation model in rats in which the donor nerves were uninjured. The regenerated axons at the coaptation site were observed directly using fluorescent dye as the neural tracer. The sciatic nerve from adult Wistar rats was transplanted between the left and right median nerves. Fifteen rats were divided into three groups. In group I, the donor (right median) nerve was sutured end to side to the divided grafted nerve using a noninjury technique. In group II, the aponeurosis of the spinal muscles was harvested and the sciatic and right median nerves were coapted end to side noninjuriously by wrapping them in the excised aponeurosis. In group III, a perineurial window was created and a partial neurectomy was carried out at the suture site, after which the sciatic and right median nerves were sutured end to side. Sixty days after the operation, nerve regeneration was evaluated by recording action potentials in the grafted nerve, by performing electromyography in the flexor muscles in the forearm, and by histological examination. The grafted nerves were fixed and sectioned, the number of regenerated nerve fibers was counted, and axonal diameters were measured. Fluorescent dye crystal was used, in conjunction with confocal microscopy, to observe the regenerated axons at the co-aptation site. The results showed that nerve regeneration had occurred in the animals, as determined electrophysiologically and histologically. Both the right and left flexor muscles of the forearm contracted simultaneously as a result of indirect electric stimulation of the grafted nerve, which suggests that the regenerated nerve was physiologically connected with the donor nerve. Nerve fiber counts did not show any differences among groups (p > 0.05), but axonal diameters were significantly greater in group III than in the other two groups. Fluorescent dye staining revealed the presence of regenerated nerve fibers beyond the coaptation site. In group III, the regenerating nerves were observed within the whole section of the coaptation site and collateral sprouting was found to occur even at a site distal to the suture. From these results, the authors conclude that in end-to-side neurorrhaphy, nerve regeneration occurs by collateral sprouting from the donor nerve.
    Plastic &amp Reconstructive Surgery 07/2004; 114(1):129-37. · 3.38 Impact Factor
  • Article: Treatment modality affects allograft-derived Schwann cell phenotype and myelinating capacity
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    ABSTRACT: We used peripheral nerve allografts, already employed clinically to reconstruct devastating peripheral nerve injuries, to study Schwann cell (SC) plasticity in adult mice. By modulating the allograft treatment modality we were able to study migratory, denervated, rejecting, and reinnervated phenotypes in transgenic mice whose SCs expressed GFP under regulatory elements of either the S100b (S100-GFP) or nestin (Nestin-GFP) promoters. Well-differentiated SCs strongly expressed S100-GFP, while Nestin-GFP expression was stimulated by denervation, and in some cases, axons were constitutively labeled with CFP to enable in vivo imaging. Serial imaging of these mice demonstrated that untreated allografts were rejected within 20 days. Cold preserved (CP) allografts required an initial phase of SC migration that preceded axonal regeneration thus delaying myelination and maturation of the SC phenotype. Mice immunosuppressed with FK506 demonstrated mild subacute rejection, but the most robust regeneration of myelinated and unmyelinated axons and motor endplate reinnervation. While characterized by fewer regenerating axons, mice treated with the co-stimulatory blockade (CSB) agents anti-CD40L mAb and CTLAIg-4 demonstrated virtually no graft rejection during the 28 day experiment, and had significant increases in myelination, connexin-32 expression, and Akt phosphorylation compared with any other group. These results indicate that even with SC rejection, nerve regeneration can occur to some degree, particularly with FK506 treatment. However, we found that co-stimulatory blockade facilitate optimal myelin formation and maturation of SCs as indicated by protein expression of myelin basic protein (MBP), connexin-32 and phospho-Akt.
    Experimental Neurology.