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Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury.
Exp Neurol. 2004 Jun; 187(2):359-66.EN

Abstract

Unilateral avulsion of lumbar ventral roots kills approximately 50% of injured motoneurons within 2 weeks of surgery. Immediate treatment involving surgical reimplantation of the ventral root (VRI) or intrathecal glial cell line-derived neurotrophic factor (GDNF) delivery or intraperitoneal injection of riluzole for 2 weeks ameliorates motoneuron death to 80% of control but combining the different treatment paradigms did not further enhance survival except when GDNF was combined with VRI. At 3 months, all combined treatments provided a neuroprotective effect compared to avulsion only, but the neuroprotective effect of surgical reimplantation alone was not maintained unless combined with riluzole and GDNF treatment. Analysis of regenerating motoneurons using retrograde labelling techniques showed that riluzole, but not GDNF, increased the number of dendrites per labelled motoneuron. However, when functional motor recovery was assessed using the BBB locomotor score and rotarod tests, only VRI animals treated with riluzole and GDNF application showed significantly improved locomotor function in both tests. Our results show that functional recovery appears related to a combination of enhanced dendrite formation, increased motoneuron survival and the neurotrophic actions of GDNF. Thus, combination treatment may offer a new therapeutic strategy for treating patients with avulsion injury.

Authors+Show Affiliations

Department of Anatomy and Developmental Biology, University College London, WC1 6BT London, UK.No 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

15144862

Citation

Bergerot, Astrid, et al. "Co-treatment With Riluzole and GDNF Is Necessary for Functional Recovery After Ventral Root Avulsion Injury." Experimental Neurology, vol. 187, no. 2, 2004, pp. 359-66.
Bergerot A, Shortland PJ, Anand P, et al. Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury. Exp Neurol. 2004;187(2):359-66.
Bergerot, A., Shortland, P. J., Anand, P., Hunt, S. P., & Carlstedt, T. (2004). Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury. Experimental Neurology, 187(2), 359-66.
Bergerot A, et al. Co-treatment With Riluzole and GDNF Is Necessary for Functional Recovery After Ventral Root Avulsion Injury. Exp Neurol. 2004;187(2):359-66. PubMed PMID: 15144862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury. AU - Bergerot,Astrid, AU - Shortland,Peter J, AU - Anand,Praveen, AU - Hunt,Stephen P, AU - Carlstedt,Thomas, PY - 2003/11/04/received PY - 2004/01/22/revised PY - 2004/02/03/accepted PY - 2004/5/18/pubmed PY - 2004/7/1/medline PY - 2004/5/18/entrez SP - 359 EP - 66 JF - Experimental neurology JO - Exp. Neurol. VL - 187 IS - 2 N2 - Unilateral avulsion of lumbar ventral roots kills approximately 50% of injured motoneurons within 2 weeks of surgery. Immediate treatment involving surgical reimplantation of the ventral root (VRI) or intrathecal glial cell line-derived neurotrophic factor (GDNF) delivery or intraperitoneal injection of riluzole for 2 weeks ameliorates motoneuron death to 80% of control but combining the different treatment paradigms did not further enhance survival except when GDNF was combined with VRI. At 3 months, all combined treatments provided a neuroprotective effect compared to avulsion only, but the neuroprotective effect of surgical reimplantation alone was not maintained unless combined with riluzole and GDNF treatment. Analysis of regenerating motoneurons using retrograde labelling techniques showed that riluzole, but not GDNF, increased the number of dendrites per labelled motoneuron. However, when functional motor recovery was assessed using the BBB locomotor score and rotarod tests, only VRI animals treated with riluzole and GDNF application showed significantly improved locomotor function in both tests. Our results show that functional recovery appears related to a combination of enhanced dendrite formation, increased motoneuron survival and the neurotrophic actions of GDNF. Thus, combination treatment may offer a new therapeutic strategy for treating patients with avulsion injury. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15144862/Co_treatment_with_riluzole_and_GDNF_is_necessary_for_functional_recovery_after_ventral_root_avulsion_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014488604000561 DB - PRIME DP - Unbound Medicine ER -