PMID- 25310564
OWN - NLM
STAT- MEDLINE
DCOM- 20150917
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 10
DP  - 2014
TI  - Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, 
      accelerates immune cell clearance and enhances remyelination in vivo in focally 
      demyelinated nerves.
PG  - e110174
LID - 10.1371/journal.pone.0110174 [doi]
LID - e110174
AB  - Rapid and efficient axon remyelination aids in restoring strong electrochemical 
      communication with end organs and in preventing axonal degeneration often 
      observed in demyelinating neuropathies. The signals from axons that can trigger 
      more effective remyelination in vivo are still being elucidated. Here we report 
      the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 
      20 Hz 5 days post-demyelination) on ensuing reparative events in a focally 
      demyelinated adult rat peripheral nerve. ES impacted many parameters underlying 
      successful remyelination. It effected increased neurofilament expression and 
      phosphorylation, both implicated in axon protection. ES increased expression of 
      myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of 
      which coincided with the early reappearance of remyelinated axons, effects not 
      observed at the same time points in non-stimulated demyelinated nerves. The 
      improved ES-associated remyelination was accompanied by enhanced clearance of 
      ED-1 positive macrophages and attenuation of glial fibrillary acidic protein 
      expression in accompanying Schwann cells, suggesting a more rapid clearance of 
      myelin debris and return of Schwann cells to a nonreactive myelinating state. 
      These benefits of ES correlated with increased levels of brain derived 
      neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the 
      initiation of the myelination program. In conclusion, the tremendous impact of 
      delayed brief nerve stimulation on enhancement of the innate capacity of a 
      focally demyelinated nerve to successfully remyelinate identifies manipulation of 
      this axis as a novel therapeutic target for demyelinating pathologies.
FAU - McLean, Nikki A
AU  - McLean NA
AD  - CMSNRC (Cameco MS Neuroscience Research Center) and Department of Anatomy and 
      Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada.
FAU - Popescu, Bogdan F
AU  - Popescu BF
AD  - CMSNRC (Cameco MS Neuroscience Research Center) and Department of Anatomy and 
      Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada.
FAU - Gordon, Tessa
AU  - Gordon T
AD  - Department of Surgery, Division of Plastic Reconstructive Surgery, University of 
      Toronto, Toronto, ON, Canada.
FAU - Zochodne, Douglas W
AU  - Zochodne DW
AD  - Department of Medicine, Division of Neurology, University of Alberta, Edmonton, 
      AB, Canada.
FAU - Verge, Valerie M K
AU  - Verge VM
AD  - CMSNRC (Cameco MS Neuroscience Research Center) and Department of Anatomy and 
      Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada.
LA  - eng
GR  - MOP74747/Canadian Institutes of Health Research/Canada
GR  - RMF82496DZ/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141013
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Stilbamidines)
SB  - IM
MH  - Animals
MH  - Axons/*metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Demyelinating Diseases/*metabolism/*pathology
MH  - Electric Stimulation
MH  - Intermediate Filaments/*metabolism
MH  - Macrophages/*metabolism
MH  - Male
MH  - Myelin Basic Protein/metabolism
MH  - Myelin Sheath/*metabolism
MH  - Nerve Tissue/*metabolism
MH  - Phosphorylation
MH  - Ranvier's Nodes/metabolism
MH  - Rats, Wistar
MH  - Schwann Cells/metabolism
MH  - Staining and Labeling
MH  - Stilbamidines/metabolism
PMC - PMC4195712
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/10/14 06:00
MHDA- 2015/09/18 06:00
PMCR- 2014/10/13
CRDT- 2014/10/14 06:00
PHST- 2014/06/10 00:00 [received]
PHST- 2014/09/17 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2015/09/18 06:00 [medline]
PHST- 2014/10/13 00:00 [pmc-release]
AID - PONE-D-14-25905 [pii]
AID - 10.1371/journal.pone.0110174 [doi]
PST - epublish
SO  - PLoS One. 2014 Oct 13;9(10):e110174. doi: 10.1371/journal.pone.0110174. 
      eCollection 2014.