PMID- 12198419 OWN - NLM STAT- MEDLINE DCOM- 20020917 LR - 20150624 IS - 0032-1052 (Print) IS - 0032-1052 (Linking) VI - 110 IP - 4 DP - 2002 Sep 15 TI - Simultaneous GDNF and BDNF application leads to increased motoneuron survival and improved functional outcome in an experimental model for obstetric brachial plexus lesions. PG - 1066-72 AB - Motoneurons of the neonate rat respond to proximal axonal injury with morphologic and functional changes and ultimately with neuronal death. Recent studies showed that both glial cell-line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) reduce induced degeneration of motoneurons after axotomy and avulsion. Whether rescued motoneurons are functionally intact has been argued. In the present investigation, the authors have used a proximal crush lesion of the brachial plexus in neonatal rats as the experimental model of neuronal injury. This allowed the authors to study the effects of trophic factor administration on injured motoneurons and the relationship between motoneuron survival and extremity function. Trophic factors were locally released by small polymer implants in a low-dose slow-release mode. Six groups of 10 animals were prepared: BDNF, GDNF, GDNF/BDNF, control, sham, and normals. The number of surviving motoneurons was determined by retrograde tracer techniques using Fluorogold and Fastblue. Extremity function was quantitatively evaluated with functional muscle testing at day 56. The results of this study demonstrate that trophic factors applied separately had no effect, whereas combined trophic factor application (GDNF/BDNF group) had a dramatic rescue effect on motoneuron survival as compared with the control groups, which also effected significantly greater strength. The authors conclude that a combination of trophic factors leads to enhanced motoneuron survival, with improved voluntary function as the animal enters adulthood so that exogenous trophic support of motoneurons might have a role in the treatment of all types of severe neonatal plexopathies, maintaining the viability of motoneurons until reconstructive surgery provides them with a pathway for regeneration and endogenous trophic support. FAU - Aszmann, Oskar C AU - Aszmann OC AD - Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical School, University of Vienna, Vienna, Austria. oskar.aszmann@univie.ac.at FAU - Korak, Klaus J AU - Korak KJ FAU - Kropf, Nina AU - Kropf N FAU - Fine, Eric AU - Fine E FAU - Aebischer, Patrick AU - Aebischer P FAU - Frey, Manfred AU - Frey M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Plast Reconstr Surg JT - Plastic and reconstructive surgery JID - 1306050 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Animals MH - Animals, Newborn MH - Brachial Plexus Neuropathies/*drug therapy/physiopathology MH - Brain-Derived Neurotrophic Factor/administration & dosage/pharmacology/*therapeutic use MH - Disease Models, Animal MH - Female MH - Glial Cell Line-Derived Neurotrophic Factor MH - Motor Neurons/*drug effects MH - Nerve Growth Factors/administration & dosage/pharmacology/*therapeutic use MH - Nerve Tissue Proteins/administration & dosage/pharmacology/*therapeutic use MH - Paralysis, Obstetric MH - Rats MH - Rats, Sprague-Dawley EDAT- 2002/08/29 10:00 MHDA- 2002/09/18 10:01 CRDT- 2002/08/29 10:00 PHST- 2002/08/29 10:00 [pubmed] PHST- 2002/09/18 10:01 [medline] PHST- 2002/08/29 10:00 [entrez] AID - 10.1097/01.PRS.0000020990.82332.43 [doi] PST - ppublish SO - Plast Reconstr Surg. 2002 Sep 15;110(4):1066-72. doi: 10.1097/01.PRS.0000020990.82332.43.