PMID- 29516218
OWN - NLM
STAT- MEDLINE
DCOM- 20190401
LR  - 20190401
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Print)
IS  - 0302-766X (Linking)
VI  - 372
IP  - 3
DP  - 2018 Jun
TI  - Neural crest stem cells protect spinal cord neurons from excitotoxic damage and 
      inhibit glial activation by secretion of brain-derived neurotrophic factor.
PG  - 493-505
LID - 10.1007/s00441-018-2808-z [doi]
AB  - The acute phase of spinal cord injury is characterized by excitotoxic and 
      inflammatory events that mediate extensive neuronal loss in the gray matter. 
      Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory 
      effects that may be mediated by soluble factors. We therefore hypothesize that 
      transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) 
      can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs 
      previously subjected to N-methyl-D-aspartate (NMDA)-induced injury. 
      Immunohistochemistry and TUNEL staining were used to quantitatively study cell 
      populations and apoptosis. Concentrations of neurotrophic factors were measured 
      by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or 
      hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of 
      NeuN-positive neurons that was otherwise observed after NMDA-induced 
      excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced 
      activation of both microglial cells and astrocytes. The concentration of 
      brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs 
      cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects 
      of NCSC application on SCSCs. NCSCs migrated superficially across the surface of 
      SCSCs and showed no signs of neuronal or glial differentiation but preserved 
      their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, 
      anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord 
      tissue, some of these effects mediated by secretion of BDNF. However, the 
      investigated NCSCs seem not to undergo neuronal or glial differentiation in the 
      short term since markers indicative of an undifferentiated state were expressed 
      during the entire observation period.
FAU - Schizas, Nikos
AU  - Schizas N
AD  - The OrthoLab, Department of Surgical Sciences, Section of Orthopaedics, Uppsala 
      University, SE-751 85, Uppsala, Sweden. nikos.schizas@surgsci.uu.se.
FAU - Konig, N
AU  - Konig N
AD  - Department of Neuroscience, Biomedicine Centre (BMC) Uppsala, BOX 593, SE-751 24, 
      Uppsala, Sweden.
FAU - Andersson, B
AU  - Andersson B
AD  - The OrthoLab, Department of Surgical Sciences, Section of Orthopaedics, Uppsala 
      University, SE-751 85, Uppsala, Sweden.
FAU - Vasylovska, S
AU  - Vasylovska S
AD  - Department of Neuroscience, Biomedicine Centre (BMC) Uppsala, BOX 593, SE-751 24, 
      Uppsala, Sweden.
FAU - Hoeber, J
AU  - Hoeber J
AD  - Department of Neuroscience, Biomedicine Centre (BMC) Uppsala, BOX 593, SE-751 24, 
      Uppsala, Sweden.
FAU - Kozlova, E N
AU  - Kozlova EN
AD  - Department of Neuroscience, Biomedicine Centre (BMC) Uppsala, BOX 593, SE-751 24, 
      Uppsala, Sweden.
FAU - Hailer, N P
AU  - Hailer NP
AD  - The OrthoLab, Department of Surgical Sciences, Section of Orthopaedics, Uppsala 
      University, SE-751 85, Uppsala, Sweden.
LA  - eng
GR  - 20716 to E.K/Vetenskapsradet/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180307
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media)
RN  - 0 (Neurotoxins)
RN  - 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Astrocytes/pathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Cell Movement/drug effects
MH  - Culture Media
MH  - Hydrogel, Polyethylene Glycol Dimethacrylate
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neural Crest/*cytology
MH  - Neural Stem Cells/*cytology/drug effects/metabolism
MH  - Neuroglia/metabolism/*pathology
MH  - Neurons/drug effects/*pathology
MH  - *Neuroprotection/drug effects
MH  - Neurotoxins/*toxicity
MH  - Spheroids, Cellular/pathology
MH  - Spinal Cord/*pathology
MH  - Spinal Cord Ventral Horn/pathology
MH  - Stem Cell Transplantation
MH  - White Matter/pathology
PMC - PMC5949140
OTO - NOTNLM
OT  - Apoptosis
OT  - Excitotoxicity
OT  - Neuroprotection
OT  - Secretion of soluble factors
OT  - Suppressed glial activation
EDAT- 2018/03/09 06:00
MHDA- 2019/04/02 06:00
PMCR- 2018/03/07
CRDT- 2018/03/09 06:00
PHST- 2017/05/31 00:00 [received]
PHST- 2018/01/24 00:00 [accepted]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2019/04/02 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
PHST- 2018/03/07 00:00 [pmc-release]
AID - 10.1007/s00441-018-2808-z [pii]
AID - 2808 [pii]
AID - 10.1007/s00441-018-2808-z [doi]
PST - ppublish
SO  - Cell Tissue Res. 2018 Jun;372(3):493-505. doi: 10.1007/s00441-018-2808-z. Epub 
      2018 Mar 7.