Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy

BMC Neuroscience

Research Article

Petr Dubový¹  Pavel Haninec²  Radek Kaiser²  Vladimír Bobek³ 

[1] Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, and Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, CZ-625 00, Brno, Czech Republic;Department of Neurosurgery, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic;Department of Tumor Biology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic;

关键词: Vascular Endothelial Growth Factor;    Dorsal Root Ganglion;    Schwann Cell;    Dorsal Root Ganglion Neuron;    Ulnar Nerve;   

DOI  :  10.1186/1471-2202-13-57

 received in 2012-02-22, accepted in 2012-06-06,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundVascular endothelial growth factor (VEGF) is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN) stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE) or end-to-side (ETS) neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles.ResultsImmunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons, behavioral test and the wet weight index of the biceps brachii muscles.ConclusionOur results showed that plasmid phVEGF transfection of MCN stumps could induce an increase in VEGF protein in Schwann cells, which resulted in higher quality axon reinnervation after both ETE and ETS neurorrhaphy. This was also associated with a better wet weight biceps brachii muscle index and functional tests than in control rats.

【 授权许可】

Unknown   
© Haninec et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.