Strain Differences in Autotomy in Rats Undergoing Sciatic Nerve Transection or Repair

Mm, Carr; Best, Timothy J.; Mackinnon, Susan E.; Evans, Peter

doi:10.1097/00000637-199206000-00008

Cited by 31 publications

(45 citation statements)

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“…Since only few alternative methods exist to noninvasively monitor sensory recovery in rodent models (Navarro, ), this should be kept in mind during assessment of mechanical pain threshold in Lewis rats. In our opinion, however, Lewis rats are still the best choice to study sciatic nerve regeneration in the context of an injury and repair animal model since this is the only rat strain known to show no automutilation so far (Carr et al, ; Shir et al, ). In accordance with the ethical concept of the 3Rs (Replacement, Reduction, Refinement; Tannenbaum and Bennett, ), a lower number of animals can be subjected to an experimental setup (Reduction) as the risk that animals have to be excluded due an increased impairment by automutilation is minimized (Refinement).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, 56 adult female Lewis rats with an average weight of 189.6 ± 1.1 g were housed in groups of four under standardized housing conditions (room temperature 22.2°C; humidity 55.5%; light/dark cycle of 14 h/10 h) with food and water provided ad libitum . Although automutilation is a phenomenon rarely seen in Lewis rats (Carr et al, ; Shir et al, ), amytriptiline hydrochloride (13.5 mg/kg/day, Amitriptylin‐neuraxpharm ® , Neuraxpharm Arzneimittel GmbH, Germany) was precautionally added to the drinking water as suggested by experts (Navarro et al, ) starting 2 weeks prior to initial surgery until the end of each substudy. Health state of the animals was controlled every 2–3 days.…”

Section: Methodsmentioning

confidence: 99%

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Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle‐in‐Vein Grafts

Stößel

Wildhagen

Helmecke³

et al. 2018

The Anatomical Record

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Reconstruction of joint-crossing digital nerves requires the application of nerve guides with a much higher flexibility than used for peripheral nerve repair along larger bones. Nevertheless, collapse-resistance should be preserved to avoid secondary damage to the regrowing nerve tissue. In recent years, we presented chitosan nerve guides (CNGs) to be highly supportive for the regeneration of critical gap length peripheral nerve defects in the rat. Now, we evidently increased the bendability of regular CNGs (regCNGs) by developing a wavy wall structure, that is, corrugated CNGs (corrCNGs). In a comprehensive in vivo study, we compared both types of CNGs with clinical gold standard autologous nerve grafts (ANGs) and muscle-in-vein grafts (MVGs) that have recently been highlighted in the literature as a suitable alternative to ANGs. We reconstructed rat sciatic nerves over a critical gap length of 15 mm either immediately upon transection or after a delay period of 45 days. Electrodiagnostic measurements were applied to monitor functional motor recovery at 60, 90, 120, and 150 (only delayed repair) days postreconstruction. Upon explanation, tube properties were analyzed. Furthermore, distal nerve ends were evaluated using histomorphometry, while connective tissue specimens were subjected to immunohistological stainings. After 120 days (acute repair) or 150 days (delayed repair), respectively, compression-stability of regCNGs was slightly increased while it remained stable in corrCNGs. In both substudies, regCNGs and corrCNGs supported functional recovery of distal plantar muscles in a similar way and to a greater extent when compared with MVGs, while ANGs demonstrated the best support of regeneration. Anat Rec, 301:1697-1713, 2018. © 2018 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle‐in‐Vein Grafts

Stößel

Wildhagen

Helmecke³

et al. 2018

The Anatomical Record

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“…In a pilot study, the effect of single and combined median and ulnar nerve lesions on reaching and grasping, grip strength, and footprint analysis was investigated. In this pilot study, female Lewis (LEW) rats (Charles River Laboratories) weighing 200 g at the start of the experiment were used because of reports that this strain is less vulnerable to autotomy ( Carr et al, 1992; Shir et al, 2001 ) . In the course of this pilot study, it became apparent that autotomy was not a problem in this forelimb model and LEW rats had poor performance in the staircase.…”

Section: Methodsmentioning

confidence: 99%

Characterization of tests of functional recovery after median and ulnar nerve injury and repair in the rat forelimb

Galtrey

Fawcett

2007

J Peripheral Nervous Sys

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The majority of human peripheral nerve injuries occur in the upper limb but the majority of studies in the rat are performed in the hindlimb. The upper and lower limbs differ in dexterity and control by supraspinal systems, so an upper limb model is a better representation of the common form of human injury. The purpose of this study was to further develop a rat model involving lesions of the median and ulnar nerves. To produce different degrees of misdirection of axons following nerve repair, we studied nerve crush, cut and repair of the two nerves, and cut and repair with crossover. Assessment of functional recovery was performed using a battery of motor and sensory tests: the staircase test, which assesses skilled forepaw reaching; grip strength meter, which assesses grip strength; pawprint analysis, which assesses toe spread and print length; horizontal ladder, which assesses forepaw placement during skilled locomotion; modified Randall-Selitto device and electronic von Frey probes, which assess fine touch; and cold probes, which assess temperature sensation. All tests revealed deficits in forepaw function after nerve injury except the print length and modified Randall-Selitto device. The time course of functional recovery was observed over 15 weeks. The final degree of functional recovery achieved was related to the misdirection of axon regeneration. The tests that most clearly revealed the effects of axon misdirection on function were the skilled paw reaching and grip strength tests. The lesion model and functional tests that we have developed will be useful in testing therapeutic strategies for treating the consequences of inaccurate axon regeneration following peripheral nerve injury in humans.

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“…Because gait is a highly dynamic and volitional behavior, it is often difficult to coax rats to walk in a straight and consistent manner, making calculation of the SFI fairly difficult. Furthermore, foot contracture and autotomy (eating the foot) can occur in up to half of all animals following sciatic denervation, precluding foot print measurement . The numerous parameters and adjustments of functional tests that have emerged to assess lower extremity rodent function over the past few years speak to the lack of a single modality that provides consistent and reliable results .…”

Section: Discussionmentioning

confidence: 99%

“…However, the study of nerve regeneration and graft reinnervation in the setting of VCA, in particular upper extremity transplantation, is currently limited by the lack of an animal model that allows for reliable assessment of behavioral functional recovery . To overcome this limitation, our group has developed a novel rat forelimb transplant model in which functional recovery is tested by measuring progressive return of grip strength and by evaluating the component upper extremity motions of the transplanted forelimb during food consumption.…”

Section: Introductionmentioning

confidence: 99%

A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration

Kern

Budihardjo

Mermulla

et al. 2017

American Journal of Transplantation

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Improved nerve regeneration and functional outcomes would greatly enhance the utility of vascularized composite allotransplantation (VCA) such as hand and upper extremity transplantation. However, research aimed at achieving this goal has been limited by the lack of a functional VCA animal model. We have developed a novel rat midhumeral forelimb transplant model that allows for the characterization of upper extremity functional recovery following transplantation. At the final end point of 12 weeks, we found that animals with forelimb transplantation including median, ulnar and radial nerve coaptation demonstrated significantly improved grip strength and forelimb function as compared to forelimb transplantation without nerve approximation (grip strength: 1.71N ± 0.57 vs. no appreciable recovery; IBB scale: 2.6 ± 0.7? vs. 0.8 ± 0.40; p = 0.0005), and similar recovery to nerve transection-and-repair only (grip strength: 1.71N ± 0.57 vs. 2.03 ± 0.42.6; IBB scale: 2.6 ± 0.7 vs. 2.8 ± 0.8; p = ns). Moreover, all forelimb transplant animals with nerve coaptation displayed robust axonal regeneration with myelination and reduced flexor muscle atrophy when compared to forelimb transplant animals without nerve coaptation. In conclusion, this is the first VCA small-animal model that allows for reliable and reproducible measurement of behavioral functional recovery in addition to histologic evaluation of nerve regeneration and graft reinnervation.

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Strain Differences in Autotomy in Rats Undergoing Sciatic Nerve Transection or Repair

Cited by 31 publications

References 0 publications

Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle‐in‐Vein Grafts

Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle‐in‐Vein Grafts

Characterization of tests of functional recovery after median and ulnar nerve injury and repair in the rat forelimb

A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration

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