Neororegeneratieve effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots
Autor: | Thomas Carlstedt, G. J. Boer, Arnaud Zaldumbide, Rob C. Hoeben, Joop J. van Heerikhuize, Chris W. Pool, Martijn R. Tannemaat, William T. Hendriks, Joost Verhaagen, Ruben Eggers |
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Přispěvatelé: | Netherlands Institute for Neuroscience (NIN) |
Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
Nerve root
Genetic Vectors Viral vector Avulsion Cellular and Molecular Neuroscience Atrophy Neurotrophic factors Ganglia Spinal Paralysis medicine Glial cell line-derived neurotrophic factor Animals Humans Glial Cell Line-Derived Neurotrophic Factor Transgenes Rats Wistar Radiculopathy Molecular Biology Cells Cultured Motor Neurons biology Regeneration (biology) Brain-Derived Neurotrophic Factor Lentivirus Cell Biology Genetic Therapy Recovery of Function medicine.disease Nerve Regeneration Rats nervous system Spinal Cord Culture Media Conditioned biology.protein Female Schwann Cells medicine.symptom Spinal Nerve Roots Neuroscience |
Zdroj: | Molecular and Cellular Neuroscience, 39, 105-117. Academic Press |
ISSN: | 1044-7431 |
Popis: | Traumatic avulsion of spinal nerve roots causes complete paralysis of the affected limb. Reimplantation of avulsed roots results in only limited functional recovery in humans, specifically of distal targets. Therefore, root avulsion causes serious and permanent disability. Here, we show in a rat model that lentiviral vector-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) in reimplanted nerve roots completely prevents motoneuron atrophy after ventral root avulsion and stimulates regeneration of axons into reimplanted roots. However, over the course of 16 weeks neuroma-like structures are formed in the reimplanted roots, and regenerating axons are trapped at sites with high levels of GDNF expression. A high local concentration of GDNF therefore impairs long distance regeneration. These observations show the feasibility of combining neurosurgical repair of avulsed roots with gene-therapeutic approaches. Our data also point to the importance of developing viral vectors that allow regulated expression of neurotrophic factors. |
Databáze: | OpenAIRE |
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