Regeneration of Denervated Skeletal Muscles – Brunelli’s CNS-PNS Paradigm • JML Journal of Medicine and Life

2019, Volume 12, Issue 4, pp 342 – 353

Regeneration of Denervated Skeletal Muscles – Brunelli’s CNS-PNS Paradigm

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Special Issues

Authors and Affiliations

von Wild Tobias ^¹

Brunelli Giorgio A. ^{² ³}

von Wild Klaus R.H. ^{⁴ ⁵ *}

Löhnhardt Marlene ^⁶

Catoi Cornel ^⁷

Catoi Adriana Florinela ^⁸

Vester Johannes C. ^⁹

Strilciuc Stefan ^¹⁰

Trillenberg Peter ^¹¹

1. 1.Department of Plastic Reconstructive and Aesthetic Surgery, Hand Surgery, Praxisklinik in der Alster City, Hamburg, Germany

2. 2.School of Specialists in Orthopedics, Traumatology, Hand and Microsurgery, University of Brescia, Brescia, Italy

3. 3.Foundation Giorgio Brunelli for Research on Spinal Cord Lesions ONLUS, E.S.C.R.I., Brescia, Italy

4. 4.Department of Neurosurgery, Medical Faculty Westphalia Wilhelm’s University Münster, Münster, Germany

5. 5.International Neuroscience Institute, Hanover, Germany

6. 6.Department of Plastic and Reconstructive Surgery, Hand Surgery, University Hospital, Hamburg, Germany

7. 7.Department of Pathology, University of Agricultural Science and Veterinary Medicine, Cluj-Napoca, Romania

8. 8.Department of Functional Biosciences, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania

9. 9.Department of Biometry & Clinical Research, idv Data Analysis and Study Planning, Gauting, Germany

10. 10.Department of Neurology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca; Romania

11. 11.Department of Neurology, University Medical Center Schleswig-Holstein, Lübeck, Germany

Corresponding Author: Klaus R.H. von Wild, MD, PhD, Prof. of Neurosurgery, Medical Faculty Westphalia Wilhelm’s University Münster, Frauenburgstr. 32, 48155 Münster, Germany, Prof. of Neurosurgical Neurorehabilitation and Re-Engineering of brain and spinal cord lesions, International Neuroscience Institute, Hanover, Germany; Phone +49-2513977750; cell +491753640400, E-mail: kvw@neurosci.de

Abstract

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians’ understanding of Brunelli’s spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry.

The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation.

A randomized study evaluating 30 rats, approved by the National Animal Ethics Advisory Committee was performed. The medication was administered postoperatively. For 14 days, 12 rats received Cerebrolysin (serum), 11 received NaCl 0.9% (shams), and 7 were controls. For microsurgery, the lateral corticospinal tract T10 was grafted to the denervated internal obliquus abdominal muscle. On day 90, intraoperative proof of reinnervation was observed. On day 100, 15 rats were euthanized for fixation, organ removal, and extensive histology-morphology examination, and the Wei-Lachin statistical procedure was employed.

After an open revision of 16 rats, 8 were CMAP positive. After intravenous Vecuronium application, two (Cerebrolysin, NaCl) out of two rats showed an incomplete compound muscle action potential (CMAP) loss due to glutamatergic and cholinergic co-transmission, while two others showed a complete loss of amplitude.

Cerebrolysin medication initiated larger restored muscle fiber diameters and less scarring. FB+ neurons were not observed in the brain but were observed in the Rexed laminae.

Brunelli’s concept was successfully replicated, demonstrating the first graft induced existence of cholinergic and glutamatergic neurotransmission in denervated grafted muscles. Statistics of the histometric count of muscle fibers revealed larger fiber diameters after Cerebrolysin.

Brunelli’s CNS-PNS experimental concept is suitable to analyze graft-neuroplasticity focused on the voluntary restoration of denervated skeletal muscles in spinal cord injury. Neuroprotection by Cerebrolysin is demonstrated.

Keywords

CNS – PNS graftBrunelli’s paradigmMuscle regenerationCerebrolysin neuromodulationTraumatic paraplegia

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JMedLife-12-342

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About this article

PMC ID: 6993288
PubMed ID: 32025252
DOI: 10.25122/jml-2019-0063

Article Publishing Date (print): Oct-Dec 2019
Available Online:

Journal information

ISSN Printing: 1844-122X
ISSN Online: 1844-3117
Journal Title: Journal of Medicine and Life

Copyright License: Open Access

This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.