PMID- 30099786 OWN - NLM STAT- MEDLINE DCOM- 20191212 LR - 20191217 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 48 IP - 5 DP - 2018 Sep TI - Granulocyte-macrophage colony-stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush. PG - 2152-2164 LID - 10.1111/ejn.14106 [doi] AB - Peripheral nerve injuries severely impair patients' quality of life as full recovery is seldom achieved. Upon axonal disruption, the distal nerve stump undergoes fragmentation, and myelin breaks down; the subsequent regeneration progression is dependent on cell debris removal. In addition to tissue clearance, macrophages release angiogenic and neurotrophic factors that contribute to axon growth. Based on the importance of macrophages for nerve regeneration, especially during the initial response to injury, we treated mice with granulocyte-macrophage colony-stimulating factor (GM-CSF) at various intervals after sciatic nerve crushing. Sciatic nerves were histologically analyzed at different time intervals after injury for the presence of macrophages and indicators of regeneration. Functional recovery was followed by an automated walking track test. We found that GM-CSF potentiated early axon growth, as indicated by the enhanced expression of growth-associated protein at 7 days postinjury. Inducible nitric oxide synthase expression increased at the beginning and at the end of the regenerative process, suggesting that nitric oxide is involved in axon growth and pruning. As expected, GM-CSF treatment stimulated macrophage infiltration, which increased at 7 and 14 days; however, it did not improve myelin clearance. Instead, GM-CSF stimulated early brain-derived neurotrophic factor (BDNF) production, which peaked at 7 days. Locomotor recovery pattern was not improved by GM-CSF treatment. The present results suggest that GM-CSF may have beneficial effects on early axonal regeneration. CI - (c) 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Bombeiro, Andre Luis AU - Bombeiro AL AD - Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, Brazil. FAU - Pereira, Bruna Toledo Nunes AU - Pereira BTN AD - Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, Brazil. FAU - de Oliveira, Alexandre Leite Rodrigues AU - de Oliveira ALR AUID- ORCID: 0000-0003-4224-4575 AD - Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180829 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Axons/drug effects/metabolism MH - Disease Models, Animal MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/*pharmacology MH - Locomotion/drug effects MH - Macrophages/*drug effects/metabolism MH - Male MH - Mice, Inbred C57BL MH - Myelin Sheath/metabolism MH - Nerve Regeneration/*drug effects MH - Peripheral Nerve Injuries/drug therapy/metabolism MH - Recovery of Function/drug effects MH - Sciatic Nerve/*drug effects/injuries MH - Wallerian Degeneration/drug therapy/metabolism OTO - NOTNLM OT - GM-CSF OT - Wallerian degeneration OT - macrophage OT - peripheral nervous system EDAT- 2018/08/14 06:00 MHDA- 2019/12/18 06:00 CRDT- 2018/08/13 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/07/15 00:00 [revised] PHST- 2018/08/01 00:00 [accepted] PHST- 2018/08/14 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2018/08/13 06:00 [entrez] AID - 10.1111/ejn.14106 [doi] PST - ppublish SO - Eur J Neurosci. 2018 Sep;48(5):2152-2164. doi: 10.1111/ejn.14106. Epub 2018 Aug 29.