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

Abstract

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.

Experimental nerve transfer model in the rat forelimb

“…for nerve transfers with synergistic function and axon count ratios are available in this animal model [30, 31]. Furthermore, using the ulnar nerve as donor and the long head of the biceps as recipient led to minimal motor or sensory deficit and thus minimal animal burden.…”

Activation of Schwann cells in vitro by magnetic nanocomposites via applied magnetic field

“…41 In addition, VEGF is an effective protein that is able to promote axonal outgrowth and SC proliferation, and moreover, to stimulate SC infiltration and neovascularization after sciatic nerve transections. 42,43 In the present study, magnetic membranes via MFs were capable of increasing the expression and secretion of BDNF, GDNF, NT-3, and VEGF in SCs, which was further enhanced when SCs were seeded within scaffolds, and moreover, the gene expression and protein secretion of these neurotrophic factors through a time-course assay were reversible, which has shown that high prolonged expression of these factors is not necessarily positive in peripheral nerve repair. 44 All these findings indicated that magnetic nanocomposites via MFs are capable of regulating the expression and secretion of multiple NTs in a synergistic way in SCs.…”

Results of nerve reconstructions in treatment of obstetrical brachial plexus injuries

“…One advantage of ETSN over end-to-end neurotization is that with ETSN there is no need to sacrifice the surrounding nerves. One possible method of achieving better results in the future may be the use of neurotrophic factors to support reinnervation [8,17]. In cases of late obstetrical brachial plexus palsy, nerve surgery will likely be ineffective, and thus secondary surgery is called for to improve the hand, forearm, elbow and shoulder function and to prevent muscle contractures and bone shortening.…”