Artificial perineurium to enhance nerve recovery from damage after neurolysis

Okui, Nobuyuki; Yamamoto, Masayuki; Fukuhira, Yukako; Kaneko, Hiroaki; Hirata, Hitoshi

doi:10.1002/mus.21727

Cited by 10 publications

(22 citation statements)

References 18 publications

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“…In addition, the honeycomb film has a smooth surface on the other side that prevents adhesion between the nerve and surrounding tissues 12. Our previous study confirmed that the honeycomb film can provide a perineurial barrier function and thus potentially expand the indications of internal neurolysis, a procedure for which the advantages and disadvantages remain controversial 16…”

Section: Discussionmentioning

confidence: 59%

“…Our previous study demonstrated that the honeycomb film not only prevented adhesion, but also compensated for the loss of perineurial barrier function. This enhanced functional recovery even after extensive internal neurolysis, a procedure that significantly damages the microvascular system within the epineurium 16. We therefore believe that wrapping with a thin, malleable, bioadhesive, biodegradable material like the honeycomb film is better than bridging the transected nerve ends using a thick, hard tubular material.…”

Section: Discussionmentioning

confidence: 98%

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A new nerve coaptation technique using a biodegradable honeycomb‐patterned film

et al. 2012

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We developed a biodegradable poly‐lactide (PLA) film with a honeycomb‐patterned porous structure (honeycomb film). This study investigated the use of this film in neurorrhaphy. Three types of PLA film were tested following bilateral sciatic nerve transection and neurorrhaphy in 35 rats: 7‐ and 10‐μm thick honeycomb films, and cast film with no porous structures. Initially, following two‐stitch neurorrhaphy, 40 limbs (20 rats) underwent wrapping in 7‐ or 10‐μm honeycomb film, cast film, no wrapping, or extra two‐stitch neurorrhaphy (8 limbs each). Breaking strength was tested 2 days postoperatively. Another 30 limbs (15 rats) then underwent wrapping in 7‐ or 10‐μm honeycomb film, cast film, no wrapping, or sham operation (six limbs each). Histological and functional analyses were performed 6 weeks postoperatively. Breaking strength was significantly higher for the 10‐μm honeycomb film than for no wrapping (P = 0.013), although no significant difference was observed between the 7‐μm honeycomb and no wrapping (P = 0.085). Breaking strength for the cast film was almost equal to that for no wrapping (P = 0.994). Extra two‐stitch (four‐stitch) neurorrhaphy was significantly stronger than all groups, except the 10‐μm honeycomb group. No significant difference was observed between the 10‐μm honeycomb and the four‐stitch (P = 0.497). No negative effects on functional recovery were identified. No adhesions or inflammation were observed between the film and surrounding tissues in the honeycomb groups. Honeycomb film may offer a suitable reinforcing material for adhesion‐free neurorrhaphy. © 2012 Wiley Periodicals, Inc. Microsurgery 2012.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 98%

A new nerve coaptation technique using a biodegradable honeycomb‐patterned film

et al. 2012

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“…Electrical pulses (supramaximal; duration, 100 ms; frequency, 1 Hz; square wave) were applied with an isolator (SS-201J; Nihon Kohden) connected to an electronic stimulator. CMAPs were recorded to estimate electrophysiological function and evaluate MCV [47], [48].…”

Section: Methodsmentioning

confidence: 99%

Targeting Anti-Inflammatory Treatment Can Ameliorate Injury-Induced Neuropathic Pain

et al. 2013

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Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. Animals were separated into 3 groups: the first group received only a skin incision; the second group received nerve crush injury and intraperitoneal vehicle injection; and the third group received nerve crush injury and intraperitoneal etanercept (6 mg/kg). Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index. Plantar thermal and von Frey mechanical withdrawal thresholds recovered faster in the etanercept group than in the control group. On day 7 after crush injury, the numbers of ED-1-positive cells in crushed nerves of the control and etanercept groups were increased compared to that in the sham-treated group. After 21 days, ED-1-positive cells had nearly disappeared from the etanercept group. Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.

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“…Scarring and adhesion represent major challenges following injury and surgical procedures of peripheral nerves, often leading to pain and even nerve dysfunction. Currently, the removal of the surrounding scar tissue (external neurolysis) up to the resection of the epifascicular fraction of the epineurium (internal neurolysis) is the most common treatment ( Mazal and Millesi, 2005 ; Okui et al, 2010 ; Frykman et al, 1981 ; Sakurai and Miyasaka, 1986 ; Calfee et al, 2008 ). However, clinical symptoms recur in most patients owing to re-appearing secondary perineural adhesions and neural fibrosis ( Abe et al, 2005 ; Botte et al, 1996 ; Dam-Hieu et al, 2005 ; Frykman et al, 1981 ; Ohsumi et al, 2005 ; Robertson, 1996 ; Rydevik et al, 1976 ), resulting in impaired nerve function ( Lundborg, 2003 ; Ngeow, 2010 ; Ohsumi et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, clinical symptoms recur in most patients owing to re-appearing secondary perineural adhesions and neural fibrosis ( Abe et al, 2005 ; Botte et al, 1996 ; Dam-Hieu et al, 2005 ; Frykman et al, 1981 ; Ohsumi et al, 2005 ; Robertson, 1996 ; Rydevik et al, 1976 ), resulting in impaired nerve function ( Lundborg, 2003 ; Ngeow, 2010 ; Ohsumi et al, 2005 ). Therefore, several different therapeutic approaches have been tested ( Doi et al, 1992 ; Varitimidis et al, 2001 ; Wintsch and Helaly, 1986 ), including implantation of muscle flaps, fat grafts ( De Smet and Vandeputte, 2002 ; Bernsmann et al, 2001 ) or diverse biomaterials ( Dam-Hieu et al, 2005 ; Ikeda et al, 2003 ; Ohsumi et al, 2005 ; Petersen et al, 1996 ; Wang et al, 1998 ), yet most therapies are still experimental and none are routinely used on patients ( Atkins et al, 2006 ; Ngeow, 2010 ; Okui et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

A novel experimental rat model of peripheral nerve scarring: reliably mimicking post-surgical complications and recurring adhesions

Lemke

Penzenstadler

Ferguson

et al. 2017

Disease Models &Amp; Mechanisms

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Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. These features can reoccur following external neurolysis, currently the most common surgical treatment for peripheral nerve scarring, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients. However, a clinically relevant model combining both histological and functional alterations has not been published to date. We therefore developed a reliable rat model that exhibits the essential pathological processes of peripheral nerve scarring. In our study, we present a novel method for the induction of nerve scarring by applying glutaraldehyde-containing glue that is known to cause nerve injury in humans. After a 3-week contact period with the sciatic nerve in female Sprague Dawley rats, we could demonstrate severe intra- and perineural scarring that resulted in grade 3 adhesions and major impairments in the electrophysiological peak amplitude compared with sham control (P=0.0478). Immunohistochemical analysis of the nerve structure revealed vigorous nerve inflammation and recruitment of T cells and macrophages. Also, distinct nerve degeneration was determined by immunostaining. These pathological alterations were further reflected in significant functional deficiencies, as determined by the analysis of relevant gait parameters as well as the quantification of the sciatic functional index starting at week 1 post-operation (P<0.01). Moreover, with this model we could, for the first time, demonstrate not only the primary formation, but also the recurrence, of severe adhesions 1 week after glue removal, imitating a major clinical challenge. As a comparison, we tested a published model for generating perineural fibrotic adhesions, which did not result in significant pathological changes. Taken together, we established an easily reproducible and reliable rat model for peripheral nerve scarring that allows for the effective testing of new therapeutic strategies.

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Artificial perineurium to enhance nerve recovery from damage after neurolysis

Cited by 10 publications

References 18 publications

A new nerve coaptation technique using a biodegradable honeycomb‐patterned film

A new nerve coaptation technique using a biodegradable honeycomb‐patterned film

Targeting Anti-Inflammatory Treatment Can Ameliorate Injury-Induced Neuropathic Pain

A novel experimental rat model of peripheral nerve scarring: reliably mimicking post-surgical complications and recurring adhesions

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