Regeneration of Denervated Skeletal Muscles – Brunelli’s CNS-PNS Paradigm
Authors: von Wild Tobias ,   Department of Plastic Reconstructive and Aesthetic Surgery, Hand Surgery, Praxisklinik in der Alster City, Hamburg, Germany, Brunelli Giorgio A. ,   School of Specialists in Orthopedics, Traumatology, Hand and Microsurgery, University of Brescia, Brescia, Italy,   Foundation Giorgio Brunelli for Research on Spinal Cord Lesions ONLUS, E.S.C.R.I., Brescia, Italy, von Wild Klaus R.H. ,   Department of Neurosurgery, Medical Faculty Westphalia Wilhelm’s University Münster, Münster, Germany,   International Neuroscience Institute, Hanover, Germany,   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, Löhnhardt Marlene ,   Department of Plastic and Reconstructive Surgery, Hand Surgery, University Hospital, Hamburg, Germany, Catoi Cornel ,   Department of Pathology, University of Agricultural Science and Veterinary Medicine, Cluj-Napoca, Romania, Florinela Catoi Adriana ,   Department of Functional Biosciences, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania, Vester Johannes C. ,   Department of Biometry & Clinical Research, idv Data Analysis and Study Planning, Gauting, Germany, Strilciuc Stefan ,   Department of Neurology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca; Romania, Trillenberg Peter ,   Department of Neurology, University Medical Center Schleswig-Holstein, Lübeck, Germany
Published: November 2022

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.