EXTRINSIC ENDONEURIAL CUES FOR SORTING OF REGENERATED SENSORY AND MOTOR AXONS IN THE PERIPHERAL NERVOUS SYSTEM

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Authors

DUBOVÝ Petr

Year of publication 2005
Type Article in Proceedings
Conference Czech Society of Histochemistry and Cytochemistry
MU Faculty or unit

Faculty of Medicine

Citation
Field Neurology, neurosurgery, neurosciences
Keywords nerve regeneration; extracellular matrix; neurotrophins
Description Correct navigation of regenerating axons into appropriate endoneurial tubes is crucial for final results of functional reinnervation after nerve repair in clinical practice. The mechanisms by which regenerating axons are guided back to their target structures are still obscure. Besides differences of intrinsic capacities of the motor and primary sensory neurons for axon regeneration, we hypothesize different cellular and extracellular conditions for regeneration of the motor and afferent axons. We used optimized indirect immunofluorescence (IF) method to investigate a composition of the endoneurial extracellular matrix (ECM) and expression of neurotrophins in the rat intact and severed dorsal (Dr) and ventral (Vr) spinal roots as well as cutaneous (Cb) and muscular (Mb) branches of femoral nerves. Intensity of IF staining (brightness) was compared using the computer-assisted image analysis. Our results of IF measurement revealed a higher amount of ECM molecules in the intact peripheral nerve branches than spinal roots. Therefore, increased amounts of the molecules distal to the root injury were more distinct than in the distal nerve stumps. The results of IF analysis also indicated different amounts of the ECM molecules between nerve compartments with dominant endoneurial tubes of motor or afferent axons. Experiments with acellular nerve segment suggested that presence of endoneurial ECM molecules depends on occurrence of living Schwann cells. In addition, results of a cross-manipulation of cellular and acellular nerve segments prepared from Cb and Mb demonstrated more beneficial extracellular conditions for regeneration and maturation of motor axons in Mb than Cb of the femoral nerve. In contrast to endoneurial ECM molecules, brightness for neurotrophins (BDNF, NGF, NT-3) was very similar in the Schwann cells of intact both spinal roots as well as Cb and Mb of the femoral nerve. All reactive Schwann cells distal to transection exhibited significantly higher IF intensity for the neurotrophins compared with the intact roots and nerves. However, spatial and temporal quantities of individual neurotrophins were variable. In conclusion, results of IF analysis suggest a quantitative difference in the extracellular and cellular molecular contents of intact and injured Dr and Vr as well as Cb and Mb of the femoral nerves, which may be involved in mechanisms for preference reinnervation of axons to the skin and muscles. The quantitative molecular differences probably promote selective reinnervation of nerve branches by native above foreign axons. Supported by the grants 309/00/0407, MSMT141100001 and MSM0021622404.
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