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A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation.
Exp Neurol. 2010 May; 223(1):207-20.EN

Abstract

Reimplantation of avulsed rat lumbar spinal ventral roots results in poor recovery of function of the denervated hind limb muscles. In contrast, reimplantation of cervical or sacral ventral roots is a successful repair strategy that results in a significant degree of regeneration. A possible explanation for this difference could be that following lumbar root avulsion, axons have to travel longer distances towards their target muscles, resulting in prolonged denervation of the distal nerve and a diminished capacity to support regeneration. Here we present a detailed spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression following unilateral avulsion and implantation of lumbar ventral roots L3, L4, and L5. Reimplantation prolongs the survival of motoneurons up to one month post-lesion. The first regenerating motor axons entered the reimplanted ventral roots during the first week and large numbers of fibers gradually enter the lumbar plexus between 2 and 4 weeks, indicating that axons enter the reimplanted roots and plexus over an extended period of time. However, motor axon counts show that relatively few axons reach the distal sciatic nerve in the 16 week post-lesion period. The observed initial increase and subsequent decline in expression of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor correlate with the apparent spatio-temporal decline in the regenerative capacity of motor axons, indicating that the distal nerve is losing its capacity to support regenerating motor axons following prolonged denervation. These findings have important implications for future strategies to promote long-distance regeneration through distal, chronically denervated peripheral nerves.

Authors+Show Affiliations

Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. r.eggers@nin.knaw.nlNo 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

19646436

Citation

Eggers, R, et al. "A Spatio-temporal Analysis of Motoneuron Survival, Axonal Regeneration and Neurotrophic Factor Expression After Lumbar Ventral Root Avulsion and Implantation." Experimental Neurology, vol. 223, no. 1, 2010, pp. 207-20.
Eggers R, Tannemaat MR, Ehlert EM, et al. A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation. Exp Neurol. 2010;223(1):207-20.
Eggers, R., Tannemaat, M. R., Ehlert, E. M., & Verhaagen, J. (2010). A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation. Experimental Neurology, 223(1), 207-20. https://doi.org/10.1016/j.expneurol.2009.07.021
Eggers R, et al. A Spatio-temporal Analysis of Motoneuron Survival, Axonal Regeneration and Neurotrophic Factor Expression After Lumbar Ventral Root Avulsion and Implantation. Exp Neurol. 2010;223(1):207-20. PubMed PMID: 19646436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation. AU - Eggers,R, AU - Tannemaat,M R, AU - Ehlert,E M, AU - Verhaagen,J, Y1 - 2009/07/28/ PY - 2009/05/29/received PY - 2009/07/08/revised PY - 2009/07/09/accepted PY - 2009/8/4/entrez PY - 2009/8/4/pubmed PY - 2010/4/17/medline SP - 207 EP - 20 JF - Experimental neurology JO - Exp. Neurol. VL - 223 IS - 1 N2 - Reimplantation of avulsed rat lumbar spinal ventral roots results in poor recovery of function of the denervated hind limb muscles. In contrast, reimplantation of cervical or sacral ventral roots is a successful repair strategy that results in a significant degree of regeneration. A possible explanation for this difference could be that following lumbar root avulsion, axons have to travel longer distances towards their target muscles, resulting in prolonged denervation of the distal nerve and a diminished capacity to support regeneration. Here we present a detailed spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression following unilateral avulsion and implantation of lumbar ventral roots L3, L4, and L5. Reimplantation prolongs the survival of motoneurons up to one month post-lesion. The first regenerating motor axons entered the reimplanted ventral roots during the first week and large numbers of fibers gradually enter the lumbar plexus between 2 and 4 weeks, indicating that axons enter the reimplanted roots and plexus over an extended period of time. However, motor axon counts show that relatively few axons reach the distal sciatic nerve in the 16 week post-lesion period. The observed initial increase and subsequent decline in expression of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor correlate with the apparent spatio-temporal decline in the regenerative capacity of motor axons, indicating that the distal nerve is losing its capacity to support regenerating motor axons following prolonged denervation. These findings have important implications for future strategies to promote long-distance regeneration through distal, chronically denervated peripheral nerves. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/19646436/A_spatio_temporal_analysis_of_motoneuron_survival_axonal_regeneration_and_neurotrophic_factor_expression_after_lumbar_ventral_root_avulsion_and_implantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(09)00287-8 DB - PRIME DP - Unbound Medicine ER -