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A novel chronic nerve compression model in the rat.

ABSTRACT: Current animal models of chronic peripheral nerve compression are mainly silicone tube models. However, the cross section of the rat sciatic nerve is not a perfect circle, and there are differences in the diameter of the sciatic nerve due to individual differences. The use of a silicone tube with a uniform internal diameter may not provide a reliable and consistent model. We have established a chronic sciatic nerve compression model that can induce demyelination of the sciatic nerve and lead to atrophy of skeletal muscle. In 3-week-old pups and adult rats, the sciatic nerve of the right hind limb was exposed, and a piece of surgical latex glove was gently placed under the nerve. N-butyl-cyanoacrylate was then placed over the nerve, and after it had set, another piece of glove latex was placed on top of the target area and allowed to adhere to the first piece to form a sandwich-like complex. Thus, a chronic sciatic nerve compression model was produced. Control pups with latex or N-butyl-cyanoacrylate were also prepared. Functional changes to nerves were assessed using the hot plate test and electromyography. Immunofluorescence and electron microscopy analyses of the nerves were performed to quantify the degree of neuropathological change. Masson staining was conducted to assess the degree of fibrosis in the gastrocnemius and intrinsic paw muscles. The pup group rats subjected to nerve compression displayed thermal hypoesthesia and a gradual decrease in nerve conduction velocity at 2 weeks after surgery. Neuropathological studies demonstrated that the model caused nerve demyelination and axonal irregularities and triggered collagen deposition in the epineurium and perineurium of the affected nerve at 8 weeks after surgery. The degree of fibrosis in the gastrocnemius and intrinsic paw muscles was significantly increased at 20 weeks after surgery. In conclusion, our novel model can reproduce the functional and histological changes of chronic nerve compression injury that occurs in humans and it will be a useful new tool for investigating the mechanisms underlying chronic nerve compression.

SUBMITTER: Liu ZY

PROVIDER: S-EPMC6108214 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A novel chronic nerve compression model in the rat.

Liu Zhen-Yu ZY Chen Zhen-Bing ZB Chen Jiang-Hai JH

Neural regeneration research 20180801 8

Current animal models of chronic peripheral nerve compression are mainly silicone tube models. However, the cross section of the rat sciatic nerve is not a perfect circle, and there are differences in the diameter of the sciatic nerve due to individual differences. The use of a silicone tube with a uniform internal diameter may not provide a reliable and consistent model. We have established a chronic sciatic nerve compression model that can induce demyelination of the sciatic nerve and lead to ...[more]

PMID: 30106062

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Project description:Clinically, peripheral nerve reconstructions in neonates are most frequently applied in brachial plexus birth injuries. Most surgical concepts, however, have investigated nerve reconstructions in adult animal models. The immature neuromuscular system reacts differently to the effects of nerve lesion and surgery and is poorly investigated due to the lack of reliable experimental models. Here, we describe an experimental forelimb model in the neonatal rat, to study these effects on both the peripheral and central nervous systems. Within 24 hours after birth, three groups were prepared: In the nerve transfer group, a lesion of the musculocutaneous nerve was reconstructed by selectively transferring the ulnar nerve. In the negative control group, the musculocutaneous nerve was divided and not reconstructed and in the positive control group, a sham surgery was performed. The animal´s ability to adapt to nerve lesions and progressive improvement over time were depict by the Bertelli test, which observes the development of grooming. Twelve weeks postoperatively, animals were fully matured and the nerve transfer successfully reinnervated their target muscles, which was indicated by muscle force, muscle weight, and cross sectional area evaluation. On the contrary, no spontaneous regeneration was found in the negative control group. In the positive control group, reference values were established. Retrograde labeling indicated that the motoneuron pool of the ulnar nerve was reduced following nerve transfer. Due to this post-axotomy motoneuron death, a diminished amount of motoneurons reinnervated the biceps muscle in the nerve transfer group, when compared to the native motoneuron pool of the musculocutaneous nerve. These findings indicate that the immature neuromuscular system behaves profoundly different than similar lesions in adult rats and explains reduced muscle force. Ultimately, pathophysiologic adaptations are inevitable. The maturing neuromuscular system, however, utilizes neonatal capacity of regeneration and seizes a variety of compensation mechanism to restore a functional extremity. The above described neonatal rat model demonstrates a constant anatomy, suitable for nerve transfers and allows all standard neuromuscular analyses. Hence, detailed investigations on the pathophysiological changes and subsequent effects of trauma on the various levels within the neuromuscular system as well as neural reorganization of the neonatal rat may be elucidated. This study was approved by the Ethics Committee of the Medical University of Vienna and the Austrian Ministry for Research and Science (BMWF-66.009/0187-WF/V/3b/2015) on March 20, 2015.

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A novel chronic nerve compression model in the rat.

Publications

A novel chronic nerve compression model in the rat.

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