PMID- 18618668
OWN - NLM
STAT- MEDLINE
DCOM- 20090316
LR  - 20240415
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 56
IP  - 16
DP  - 2008 Dec
TI  - Down-regulation of neurocan expression in reactive astrocytes promotes axonal 
      regeneration and facilitates the neurorestorative effects of bone marrow stromal 
      cells in the ischemic rat brain.
PG  - 1747-54
LID - 10.1002/glia.20722 [doi]
AB  - The glial scar, a primarily astrocytic structure bordering the infarct tissue 
      inhibits axonal regeneration after stroke. Neurocan, an axonal extension 
      inhibitory molecule, is up-regulated in the scar region after stroke. Bone marrow 
      stromal cells (BMSCs) reduce the thickness of glial scar wall and facilitate 
      axonal remodeling in the ischemic boundary zone. To further clarify the role of 
      BMSCs in axonal regeneration and its underlying mechanism, the current study 
      focused on the effect of BMSCs on neurocan expression in the ischemic brain. 
      Thirty-one adult male Wistar rats were subjected to 2 h of middle cerebral artery 
      occlusion followed by an injection of 3 x 10(6) rat BMSCs (n = 16) or 
      phosphate-buffered saline (n = 15) into the tail vein 24 h later. Animals were 
      sacrificed at 8 days after stroke. Immunostaining analysis showed that reactive 
      astrocytes were the primary source of neurocan, and BMSC-treated animals had 
      significantly lower neurocan and higher growth associated protein 43 expression 
      in the penumbral region compared with control rats, which was confirmed by 
      Western blot analysis of the brain tissue. To further investigate the effects of 
      BMSCs on astrocyte neurocan expression, single reactive astrocytes were collected 
      from the ischemic boundary zone using laser capture microdissection. Neurocan 
      gene expression was significantly down-regulated in rats receiving BMSC 
      transplantation (n = 4/group). Primary cultured astrocytes showed similar 
      alterations; BMSC coculture during reoxygenation abolished the up-regulation of 
      neurocan gene in astrocytes undergoing oxygen-glucose deprivation (n = 3/group). 
      Our data suggest that BMSCs promote axonal regeneration by reducing neurocan 
      expression in peri-infarct astrocytes.
CI  - Copyright 2008 Wiley-Liss, Inc.
FAU - Shen, Li Hong
AU  - Shen LH
AD  - Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
FAU - Li, Yi
AU  - Li Y
FAU - Gao, Qi
AU  - Gao Q
FAU - Savant-Bhonsale, Smita
AU  - Savant-Bhonsale S
FAU - Chopp, Michael
AU  - Chopp M
LA  - eng
GR  - P01 NS042345-05/NS/NINDS NIH HHS/United States
GR  - P01 NS42345/NS/NINDS NIH HHS/United States
GR  - R01 NS45041/NS/NINDS NIH HHS/United States
GR  - R01 NS045041/NS/NINDS NIH HHS/United States
GR  - R01 NS045041-04/NS/NINDS NIH HHS/United States
GR  - P01 NS042345/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Chondroitin Sulfate Proteoglycans)
RN  - 0 (GAP-43 Protein)
RN  - 0 (Ncan protein, mouse)
RN  - 0 (Ncan protein, rat)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurocan)
RN  - 0 (Proteoglycans)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Bone Marrow Transplantation/*methods
MH  - Brain Infarction/metabolism/physiopathology/therapy
MH  - Cells, Cultured
MH  - Chondroitin Sulfate Proteoglycans/*metabolism
MH  - Down-Regulation/physiology
MH  - GAP-43 Protein/metabolism
MH  - Gliosis/metabolism/physiopathology
MH  - Growth Cones/metabolism/ultrastructure
MH  - Hypoxia-Ischemia, Brain/*metabolism/physiopathology/*therapy
MH  - Infarction, Middle Cerebral Artery/metabolism/physiopathology/therapy
MH  - Male
MH  - Nerve Regeneration/*physiology
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurocan
MH  - Proteoglycans/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Recovery of Function/physiology
MH  - Stromal Cells/physiology/*transplantation
PMC - PMC2575136
MID - NIHMS65211
EDAT- 2008/07/12 09:00
MHDA- 2009/03/17 09:00
PMCR- 2009/12/01
CRDT- 2008/07/12 09:00
PHST- 2008/07/12 09:00 [pubmed]
PHST- 2009/03/17 09:00 [medline]
PHST- 2008/07/12 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - 10.1002/glia.20722 [doi]
PST - ppublish
SO  - Glia. 2008 Dec;56(16):1747-54. doi: 10.1002/glia.20722.