Most cited article - PubMed ID 21696588
Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy
BACKGROUND: Vascular 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. RESULTS: Immunohistochemical 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. CONCLUSION: Our 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.
- MeSH
- Dextrans MeSH
- Fluoresceins MeSH
- Genetic Therapy methods MeSH
- Rats MeSH
- Spinal Cord pathology MeSH
- Disease Models, Animal MeSH
- Peripheral Nervous System Diseases pathology therapy MeSH
- Nerve Fibers, Myelinated pathology MeSH
- Musculocutaneous Nerve metabolism pathology physiology MeSH
- Neurologic Examination MeSH
- Neurons metabolism pathology MeSH
- Rats, Wistar MeSH
- Forelimb physiopathology MeSH
- Nerve Regeneration genetics physiology MeSH
- Rhodamines MeSH
- Vascular Endothelial Growth Factor A biosynthesis metabolism therapeutic use MeSH
- Organ Size physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dextrans MeSH
- Fluoresceins MeSH
- fluoro-emerald MeSH Browser
- Fluoro-Ruby MeSH Browser
- Rhodamines MeSH
- Vascular Endothelial Growth Factor A MeSH