PMID- 26506253
OWN - NLM
STAT- MEDLINE
DCOM- 20170724
LR  - 20181113
IS  - 1878-1519 (Electronic)
IS  - 1569-9048 (Print)
IS  - 1569-9048 (Linking)
VI  - 226
DP  - 2016 Jun
TI  - Functional recovery after cervical spinal cord injury: Role of neurotrophin and 
      glutamatergic signaling in phrenic motoneurons.
PG  - 128-36
LID - S1569-9048(15)30063-X [pii]
LID - 10.1016/j.resp.2015.10.009 [doi]
AB  - Cervical spinal cord injury (SCI) interrupts descending neural drive to phrenic 
      motoneurons causing diaphragm muscle (DIAm) paralysis. Recent studies using a 
      well-established model of SCI, unilateral spinal hemisection of the C2 segment of 
      the cervical spinal cord (SH), provide novel information regarding the molecular 
      and cellular mechanisms of functional recovery after SCI. Over time post-SH, 
      gradual recovery of rhythmic ipsilateral DIAm activity occurs. Recovery of 
      ipsilateral DIAm electromyogram (EMG) activity following SH is enhanced by 
      increasing brain-derived neurotrophic factor (BDNF) in the region of the phrenic 
      motoneuron pool. Delivery of exogenous BDNF either via intrathecal infusion or 
      via mesenchymal stem cells engineered to release BDNF similarly enhance recovery. 
      Conversely, recovery after SH is blunted by quenching endogenous BDNF with the 
      fusion-protein TrkB-Fc in the region of the phrenic motoneuron pool or by 
      selective inhibition of TrkB kinase activity using a chemical-genetic approach in 
      TrkB(F616A) mice. Furthermore, the importance of BDNF signaling via TrkB 
      receptors at phrenic motoneurons is highlighted by the blunting of recovery by 
      siRNA-mediated downregulation of TrkB receptor expression in phrenic motoneurons 
      and by the enhancement of recovery evident following virally-induced increases in 
      TrkB expression specifically in phrenic motoneurons. BDNF/TrkB signaling 
      regulates synaptic plasticity in various neuronal systems, including 
      glutamatergic pathways. Glutamatergic neurotransmission constitutes the main 
      inspiratory-related, excitatory drive to motoneurons, and following SH, 
      spontaneous neuroplasticity is associated with increased expression of ionotropic 
      N-methyl-d-aspartate (NMDA) receptors in phrenic motoneurons. Evidence for the 
      role of BDNF/TrkB and glutamatergic signaling in recovery of DIAm activity 
      following cervical SCI is reviewed.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Gill, Luther C
AU  - Gill LC
AD  - Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 
      55906, United States.
FAU - Gransee, Heather M
AU  - Gransee HM
AD  - Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 
      55906, United States.
FAU - Sieck, Gary C
AU  - Sieck GC
AD  - Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 
      55906, United States; Department of Anesthesiology, Mayo Clinic, Rochester, MN 
      55906, United States.
FAU - Mantilla, Carlos B
AU  - Mantilla CB
AD  - Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 
      55906, United States; Department of Anesthesiology, Mayo Clinic, Rochester, MN 
      55906, United States. Electronic address: mantilla.carlos@mayo.edu.
LA  - eng
GR  - R01 HL096750/HL/NHLBI NIH HHS/United States
GR  - T32 HL105355/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20151023
PL  - Netherlands
TA  - Respir Physiol Neurobiol
JT  - Respiratory physiology & neurobiology
JID - 101140022
RN  - 0 (Nerve Growth Factors)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Cervical Cord/*injuries/*metabolism
MH  - Glutamic Acid/metabolism
MH  - Humans
MH  - Motor Neurons/metabolism
MH  - Nerve Growth Factors/metabolism
MH  - Phrenic Nerve/metabolism
MH  - Recovery of Function/*physiology
MH  - *Respiration
MH  - Signal Transduction
MH  - Spinal Cord Injuries/*metabolism
PMC - PMC4842164
MID - NIHMS738011
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Diaphragm muscle
OT  - Phrenic motoneuron
OT  - Respiration
OT  - Trk receptor
EDAT- 2015/10/28 06:00
MHDA- 2017/07/25 06:00
PMCR- 2017/06/01
CRDT- 2015/10/28 06:00
PHST- 2015/08/04 00:00 [received]
PHST- 2015/10/15 00:00 [revised]
PHST- 2015/10/17 00:00 [accepted]
PHST- 2015/10/28 06:00 [entrez]
PHST- 2015/10/28 06:00 [pubmed]
PHST- 2017/07/25 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - S1569-9048(15)30063-X [pii]
AID - 10.1016/j.resp.2015.10.009 [doi]
PST - ppublish
SO  - Respir Physiol Neurobiol. 2016 Jun;226:128-36. doi: 10.1016/j.resp.2015.10.009. 
      Epub 2015 Oct 23.