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Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots.
Mol Cell Neurosci. 2008 Sep; 39(1):105-17.MC

Abstract

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.

Authors+Show Affiliations

Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18585464

Citation

Eggers, Ruben, et al. "Neuroregenerative Effects of Lentiviral Vector-mediated GDNF Expression in Reimplanted Ventral Roots." Molecular and Cellular Neurosciences, vol. 39, no. 1, 2008, pp. 105-17.
Eggers R, Hendriks WT, Tannemaat MR, et al. Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots. Mol Cell Neurosci. 2008;39(1):105-17.
Eggers, R., Hendriks, W. T., Tannemaat, M. R., van Heerikhuize, J. J., Pool, C. W., Carlstedt, T. P., Zaldumbide, A., Hoeben, R. C., Boer, G. J., & Verhaagen, J. (2008). Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots. Molecular and Cellular Neurosciences, 39(1), 105-17. https://doi.org/10.1016/j.mcn.2008.05.018
Eggers R, et al. Neuroregenerative Effects of Lentiviral Vector-mediated GDNF Expression in Reimplanted Ventral Roots. Mol Cell Neurosci. 2008;39(1):105-17. PubMed PMID: 18585464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots. AU - Eggers,Ruben, AU - Hendriks,William T J, AU - Tannemaat,Martijn R, AU - van Heerikhuize,Joop J, AU - Pool,Chris W, AU - Carlstedt,Thomas P, AU - Zaldumbide,Arnaud, AU - Hoeben,Rob C, AU - Boer,Gerard J, AU - Verhaagen,Joost, Y1 - 2008/06/07/ PY - 2008/04/28/received PY - 2008/05/28/revised PY - 2008/05/28/accepted PY - 2008/7/1/pubmed PY - 2008/10/31/medline PY - 2008/7/1/entrez SP - 105 EP - 17 JF - Molecular and cellular neurosciences JO - Mol. Cell. Neurosci. VL - 39 IS - 1 N2 - 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. SN - 1095-9327 UR - https://www.unboundmedicine.com/medline/citation/18585464/Neuroregenerative_effects_of_lentiviral_vector_mediated_GDNF_expression_in_reimplanted_ventral_roots_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-7431(08)00141-3 DB - PRIME DP - Unbound Medicine ER -