PMID- 24910201 OWN - NLM STAT- MEDLINE DCOM- 20141217 LR - 20211021 IS - 1090-2430 (Electronic) IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 261 DP - 2014 Nov TI - TrkB kinase activity is critical for recovery of respiratory function after cervical spinal cord hemisection. PG - 190-5 LID - S0014-4886(14)00186-1 [pii] LID - 10.1016/j.expneurol.2014.05.027 [doi] AB - Neuroplasticity following spinal cord injury contributes to spontaneous recovery over time. Recent studies highlight the important role of brain-derived neurotrophic factor (BDNF) signaling via the high-affinity tropomyosin-related kinase (Trk) receptor subtype B (TrkB) in recovery of rhythmic diaphragm activity following unilateral spinal hemisection at C2 (C2SH). We hypothesized that TrkB kinase activity is necessary for spontaneous recovery of diaphragm activity post-C2SH. A chemical-genetic approach employing adult male TrkB(F616A) mice (n=49) was used to determine the impact of inhibiting TrkB kinase activity by the phosphoprotein phosphatase 1 inhibitor derivative 1NMPP1 on recovery of ipsilateral hemidiaphragm EMG activity. In mice, C2SH was localized primarily to white matter tracts comprising the lateral funiculus. The extent of damaged spinal cord (~27%) was similar regardless of the presence of functional recovery, consistent with spontaneous recovery reflecting neuroplasticity primarily of contralateral spared descending pathways to the phrenic motor pools. Ipsilateral hemidiaphragm EMG activity was verified as absent in all mice at 3days post-C2SH. By 2weeks after C2SH, ipsilateral hemidiaphragm EMG activity was present in 39% of vehicle-treated mice compared to 7% of 1NMPP1-treated mice (P=0.03). These data support the hypothesis that BDNF/TrkB signaling involving TrkB kinase activity plays a critical role in spontaneous recovery of diaphragm activity following cervical spinal cord injury. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Mantilla, Carlos B AU - Mantilla CB AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: mantilla.carlos@mayo.edu. FAU - Greising, Sarah M AU - Greising SM AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. FAU - Stowe, Jessica M AU - Stowe JM AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. FAU - Zhan, Wen-Zhi AU - Zhan WZ AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. FAU - Sieck, Gary C AU - Sieck GC AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. LA - eng GR - R01 HL096750/HL/NHLBI NIH HHS/United States GR - T32 HL105355/HL/NHLBI NIH HHS/United States GR - HL096750/HL/NHLBI NIH HHS/United States GR - HL105355/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140605 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (1NMPP1 compound) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Analysis of Variance MH - Animals MH - Cervical Cord MH - Diaphragm/physiopathology MH - Disease Models, Animal MH - Electromyography MH - Functional Laterality/*physiology MH - Male MH - Mice MH - Mice, Transgenic MH - Mutation/genetics MH - Protein Kinase Inhibitors/pharmacology MH - Pyrazoles/pharmacology MH - Pyrimidines/pharmacology MH - Receptor, trkB/genetics/*metabolism MH - Recovery of Function/drug effects/*physiology MH - Respiration Disorders/*etiology MH - Spinal Cord Injuries/*complications/pathology MH - Time Factors PMC - PMC4194245 MID - NIHMS619521 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Diaphragm muscle OT - EMG OT - Spinal cord injury EDAT- 2014/06/10 06:00 MHDA- 2014/12/18 06:00 PMCR- 2015/11/01 CRDT- 2014/06/10 06:00 PHST- 2014/01/24 00:00 [received] PHST- 2014/05/27 00:00 [revised] PHST- 2014/05/30 00:00 [accepted] PHST- 2014/06/10 06:00 [entrez] PHST- 2014/06/10 06:00 [pubmed] PHST- 2014/12/18 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - S0014-4886(14)00186-1 [pii] AID - 10.1016/j.expneurol.2014.05.027 [doi] PST - ppublish SO - Exp Neurol. 2014 Nov;261:190-5. doi: 10.1016/j.expneurol.2014.05.027. Epub 2014 Jun 5.