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Vascular endothelial growth factor (VEGF) represents one of the main factors involved not only in angiogenesis and vasculogenesis but also in neuritogenesis. VEGF plays its function acting via different receptors: VEGF receptor1 (VEGFR-1), VEGF receptor2 (VEGFR-2), VEGF receptor3 (VEGFR-3), and co-receptors Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). This study reports on the first in vivo analysis of the expression of VEGF and VEGF family molecules in peripheral nerve degeneration and regeneration: for this purpose, different models of nerve lesion in rat were adopted, the median nerve crush injury and the median nerve transaction followed or not by end-to end microsurgical repair. Results obtained by real time polymerase chain reaction showed that VEGF and VEGF family molecules are differentially expressed under regenerating and degenerating condition, furthermore, in order to study the modulation and involvement of these factors in two different regenerative models, crush injury and end-to-end repair, protein expression analysis was evaluated. In addition, immunohistochemical analysis allowed to state a glial localization of VEGF and VEGFR-2 after peripheral nerve crush injury. Finally in vitro assay on primary Schwann cells culture show that VEGF165 stimulation increases Schwann cells migration, a major process in the promotion of neurite outgrowth. Anat Rec, 301:1646-1656, 2018. © 2018 Wiley Periodicals, Inc.

The therapeutic effect of three polyvinyl alcohol (PVA) membranes loaded with electrically conductive materials - carbon nanotubes (PVA-CNTs) and polypyrrole (PVA-PPy) - were tested in vivo for neuro-muscular regeneration after an axonotmesis injury in the rat sciatic nerve. The membranes electrical conductivity measured was 1.5 ± 0.5 × 10

The last 15 years have seen a growing interest regarding a technique for nerve repair named end-to-side coaptation. Since 2000, we have carried out experimental studies on end-to-side nerve repair as well as employed this technique to a series of selected clinical cases. Here we report on the results of this experience.For experimental studies, we have used the model represented by median nerve repair by end-to-side coaptation either on the ulnar (agonistic) or the radial (antagonistic) nerve. For time course assessment of median nerve functional recovery we used the grasping test, a test which permits to assess voluntary control of muscle function. Repaired nerves were processed for resin embedding to allow nerve fibre stereology and electron microscopy. Results showed that, in either experimental group, end-to-side-repaired median nerves were repopulated by axons regenerating from ulnar and radial donor nerves, respectively. Moreover, contrary to previously published data, our results showed that voluntary motor control of the muscles innervated by the median nerve was progressively recovered also when the antagonistic radial nerve was the donor nerve.As regards our clinical experience, results were not so positive. We have treated by end-to-side coaptation patients with both sensory (n = 7, collateral digital nerves) and mixed (n = 8, plexus level) nerve lesions. Results were good, as in other series, in sensory nerves whilst they were very difficult to investigate in mixed nerves at the plexus level.Take together, these results suggest that clinical employment of end-to-side coaptation should still be considered at the moment as the ultima ratio in cases in which no other repair technique can be attempted. Yet, it is clear that more basic research is needed to explain the reasons for the different results between laboratory animal and humans and, especially, to find out how to ameliorate the outcome of end-to-side nerve repair by adequate treatment and rehabilitation.

Peripheral nerve researchers frequently use the rat sciatic nerve crush model in order to test different therapeutic approaches. The purpose of this study was to determine the sequence of changes after an axonotmetic injury by means of a biomechanical model of the foot and ankle, and compare them with walking track analysis, over a fixed period of time. A kinematic analysis program was used to acquire ankle motion data for further analysis. Although repeated measures analysis of variance showed significant cumulative changes induced by the crush lesion for both ankle kinematic parameters and sciatic functional index, post-hoc multiple comparisons by the Student-Neuman-Keuls test revealed significant differences between week 0 and week 8 only for ankle kinematics. These results are of importance in showing the superiority of ankle kinematics in detecting small biomechanical deficits related to hyperexcitability of the plantarflexor muscles, in contrast with walking track analysis, which showed full motor functional recovery 8 weeks after the crush lesion.

Peripheral nerves are subject to many different types of injuries frequently and these injuries may result in partial or total loss of motor and sensory functions. In contrast to the central nervous system, peripheral nervous system are able to undergo spontaneous regeneration. But clinical and experimental studies show that this regeneration is mostly not satisfactory. One of the most important neuropathological indicators of nerve regeneration is quantitative estimation of myelinated axons. Quantitative estimation of the total number of myelinated fibers can be obtained both by light microscopy (LM) and electron microscopy (EM) and depends on using appropriate sampling strategy. In this study, we made a direct comparison between LM and EM estimation of myelinated nerve fibers. Ten female Wistar albino rats were divided into two experimental groups; control group (n=5) and gap group (n=5). In the gap group, 5 mm right sciatic nerve segment of rats were resected to form a gap. Proximal and distal nerve stumps were surrounded by collagen membrane following resection. In the control group, rats received neither any operation nor any treatment. Rats were sacrificed at 12 week after surgery. Nerve samples were embedded in resin. Semi and ultra thin sections (of 1 μm and 100 nm thickness, respectively) were cut and stained with 1% toluidine blue (for LM) and uranyl acetate-lead citrate (for EM). Histological assessment of myelinated fibers was performed with both LM and EM using unbiased stereological counting techniques. There was a significant difference in the total number of myelinated nerve fibers between LM and EM examinations in terms of the both pure and regenerating axons. This difference is probably related to different magnification capacities in LM and EM. LM causes to underestimates as a result of possessing very small myelinated fibers, which are only detectable with EM. According to our results it may be concluded that the combination of both light and electron microscopical results is essential especially in revealing regenerating nerve fibers since very small myelinated fibers can not be distinguishable with LM.

Hypertrophy of the smooth muscle wall of the rat small intestine occurs in the loops upstream from a partial surgical stenosis. This phenomenon is due both to cell hypertrophy and cell proliferation (hyperplasia). The thickness of the muscular layers reached its maximum after ten days from the intervention and then was maintained over the following days. Hyperplasia of the smooth muscle tissue has been demonstrated by means of autoradiography after administration of tritiated-thymidine. This investigation revealed the presence of 37%-44.5% of heavily labeled smooth muscle nuclei, index of active DNA neo-synthesis. On the contrary, no labeled nuclei were observed in the downstream tract as well as in the small intestine of the controls. These results, together with those obtained by other researchers, confirms that the smooth muscle tissue can undergo cell proliferation under particular conditions and that this phenomenon is often associated with the hypertrophic process.