Since peripheral nerves injuries have high worldwide prevalence and incidence, in the last decade the experimental investigation about nerve function recovery is rising. Unlike central nervous tissue, peripheral nerve fibers are able to functionally regenerate due to their permissive environment. The understanding of nerve regeneration mechanisms is interesting to indentify new molecular targets to facilitate and speed up the physiological injury recover and to improve the post-operative outcome. Schwann cells are key elements in this process but the biomolecular signals driving the regeneration have not been completely characterized. Recent data shown that neuregulin-mediated HER family (Human Epidermal growth factor Receptor, transmembrane receptor with tyrosine kinase activity), in particular ErbB2, is involved in the regulation of Schwann cells activity, and hence in the molecular response to peripheral nerve injuries. To study the involvement of ErbB2 in the biological process of spontaneous nerve regeneration, we analyzed the condition after a crush injury in genetically modified mice over-expressing this receptor compared to wild type mice used as controls. Postoperative recovery was regularly evaluated by the grasping test: results indicate that functional recovery of the transgenic mice is significantly higher than the control ones starting from the 1st week. Nerve fibers regeneration was assessed by quantitative stereology of myelinated ones: the transgenic mice show a very evident increase in the total fiber number which is more than sixty percent, and it is significant compared to WT mice (see figure). Preliminary results show that over-expression of ErbB2 induces a faster recovery after crush injury, and morphological analysis demonstrates that this is probably due to an increased number of regenerated axons. This study may provide the biological basis for an innovative clinical strategy for promoting nerve regeneration after lesion through the pharmacological manipulation of Erb system.
Median nerve regeneration is increased in ErbB2 transgenic mice
SALAMONE, PAOLINA;DI SCIPIO, FEDERICA;RONCHI, GIULIA;SPRIO, ANDREA ELIO;TOS, PIERLUIGI;GEUNA, Stefano;BERTA, Giovanni Nicolao
2009-01-01
Abstract
Since peripheral nerves injuries have high worldwide prevalence and incidence, in the last decade the experimental investigation about nerve function recovery is rising. Unlike central nervous tissue, peripheral nerve fibers are able to functionally regenerate due to their permissive environment. The understanding of nerve regeneration mechanisms is interesting to indentify new molecular targets to facilitate and speed up the physiological injury recover and to improve the post-operative outcome. Schwann cells are key elements in this process but the biomolecular signals driving the regeneration have not been completely characterized. Recent data shown that neuregulin-mediated HER family (Human Epidermal growth factor Receptor, transmembrane receptor with tyrosine kinase activity), in particular ErbB2, is involved in the regulation of Schwann cells activity, and hence in the molecular response to peripheral nerve injuries. To study the involvement of ErbB2 in the biological process of spontaneous nerve regeneration, we analyzed the condition after a crush injury in genetically modified mice over-expressing this receptor compared to wild type mice used as controls. Postoperative recovery was regularly evaluated by the grasping test: results indicate that functional recovery of the transgenic mice is significantly higher than the control ones starting from the 1st week. Nerve fibers regeneration was assessed by quantitative stereology of myelinated ones: the transgenic mice show a very evident increase in the total fiber number which is more than sixty percent, and it is significant compared to WT mice (see figure). Preliminary results show that over-expression of ErbB2 induces a faster recovery after crush injury, and morphological analysis demonstrates that this is probably due to an increased number of regenerated axons. This study may provide the biological basis for an innovative clinical strategy for promoting nerve regeneration after lesion through the pharmacological manipulation of Erb system.
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