PMID- 30254669 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1687-5443 (Electronic) IS - 2090-5904 (Print) IS - 1687-5443 (Linking) VI - 2018 DP - 2018 TI - Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats. PG - 7975013 LID - 10.1155/2018/7975013 [doi] LID - 7975013 AB - Botulinum neurotoxin A (BoNT) and brain-derived neurotrophic factor (BDNF) are known for their ability to influence synaptic inputs to neurons. Here, we tested if these drugs can modulate the deafferentation of motoneurons following nerve section/suture and, as a consequence, modify the outcome of peripheral nerve regeneration. We applied drug solutions to the proximal stump of the freshly cut femoral nerve of adult rats to achieve drug uptake and transport to the neuronal perikarya. The most marked effect of this application was a significant reduction of the axotomy-induced loss of perisomatic cholinergic terminals by BoNT at one week and two months post injury. The attenuation of the synaptic deficit was associated with enhanced motor recovery of the rats 2-20 weeks after injury. Although BDNF also reduced cholinergic terminal loss at 1 week, it had no effect on this parameter at two months and no effect on functional recovery. These findings strengthen the idea that persistent partial deafferentation of axotomized motoneurons may have a significant negative impact on functional outcome after nerve injury. Intraneural application of drugs may be a promising way to modify deafferentation and, thus, elucidate relationships between synaptic plasticity and restoration of function. FAU - Irintchev, Marcel AU - Irintchev M AD - Department of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. FAU - Guntinas-Lichius, Orlando AU - Guntinas-Lichius O AUID- ORCID: 0000-0001-9671-0784 AD - Department of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. FAU - Irintchev, Andrey AU - Irintchev A AUID- ORCID: 0000-0002-4637-1259 AD - Department of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. LA - eng PT - Journal Article DEP - 20180905 PL - United States TA - Neural Plast JT - Neural plasticity JID - 100883417 RN - EC 3.4.24.69 (Botulinum Toxins, Type A) SB - IM MH - Animals MH - Axons/drug effects MH - Axotomy MH - Botulinum Toxins, Type A/*administration & dosage MH - Female MH - Femoral Nerve/*drug effects/injuries MH - Motor Neurons/drug effects MH - Nerve Regeneration/*drug effects MH - Rats MH - Rats, Wistar MH - Recovery of Function/*drug effects MH - Synapses/drug effects PMC - PMC6145158 EDAT- 2018/09/27 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/09/05 CRDT- 2018/09/27 06:00 PHST- 2018/03/06 00:00 [received] PHST- 2018/07/15 00:00 [revised] PHST- 2018/08/05 00:00 [accepted] PHST- 2018/09/27 06:00 [entrez] PHST- 2018/09/27 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/09/05 00:00 [pmc-release] AID - 10.1155/2018/7975013 [doi] PST - epublish SO - Neural Plast. 2018 Sep 5;2018:7975013. doi: 10.1155/2018/7975013. eCollection 2018.