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