PMID- 30706307
OWN - NLM
STAT- MEDLINE
DCOM- 20190626
LR  - 20211007
IS  - 1573-9686 (Electronic)
IS  - 0090-6964 (Linking)
VI  - 47
IP  - 4
DP  - 2019 Apr
TI  - Repeated In Vitro Impact Conditioning of Astrocytes Decreases the Expression and 
      Accumulation of Extracellular Matrix.
PG  - 967-979
LID - 10.1007/s10439-019-02219-y [doi]
AB  - Pathological changes to the physical and chemical properties of brain 
      extracellular matrix (ECM) occur following injury. It is generally assumed that 
      astrocytes play an important role in these changes. What remain unclear are the 
      triggers that lead to changes in the regulation of ECM by astrocytes following 
      injury. We hypothesize that mechanical stimulation triggers genotypic and 
      phenotypic changes to astrocytes that could ultimately reshape the ECM 
      composition of the central nervous system following injury. To explore astrocyte 
      mechanobiology, an in vitro drop test bioreactor was employed to condition 
      primary rat astrocytes using short duration (10 ms), high deceleration (150G) and 
      strain (20%) impact stimuli. Experiments were designed to explore the effect of 
      single and repeated impact (single vs. double) on mechano-sensitive behavior 
      including cell viability; ECM gene (collagens I and IV, fibronectin, neurocan, 
      versican) and reactivity gene [glial fibrillary acidic protein (GFAP), S100B, 
      vimentin] expression; matrix regulatory cytokine secretion [matrix 
      metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 1 (TIMP1), 
      transforming growth factor beta 1 (TGFbeta1)]; and matrix accumulation [collagen and 
      glycosaminoglycan (GAG)]. Experiments revealed that both ECM and reactive gliosis 
      gene expression was significantly decreased in response to impact conditioning. 
      The decreases for several genes, including collagen, versican, and GFAP were 
      sensitive to impact number, suggesting mechano-sensitivity to repeated impact 
      conditioning. The measured decreases in ECM gene expression were supported by 
      longer-term in vitro experiments that demonstrated significant decreases in 
      chondroitin sulfate proteoglycan (CSPG) and collagen accumulation within impact 
      conditioned 3-D scaffolds accompanied by a 25% decrease in elastic modulus. 
      Overall, the general trend across all samples was towards altered ECM and 
      reactive gliosis gene expression in response to impact. These results suggest 
      that the regulation of ECM production by astrocytes is sensitive to mechanical 
      stimuli, and that repeated impact conditioning may increase this sensitivity.
FAU - Walker, Addison
AU  - Walker A
AD  - Department of Biomedical Engineering, University of Arkansas, 125 Engineering 
      Hall, Fayetteville, AR, 72701, USA.
FAU - Kim, Johntaehwan
AU  - Kim J
AD  - Department of Biomedical Engineering, University of Arkansas, 125 Engineering 
      Hall, Fayetteville, AR, 72701, USA.
FAU - Wyatt, Joseph
AU  - Wyatt J
AD  - Department of Biomedical Engineering, University of Arkansas, 125 Engineering 
      Hall, Fayetteville, AR, 72701, USA.
FAU - Terlouw, Abby
AU  - Terlouw A
AD  - Department of Biomedical Engineering, University of Arkansas, 125 Engineering 
      Hall, Fayetteville, AR, 72701, USA.
FAU - Balachandran, Kartik
AU  - Balachandran K
AD  - Department of Biomedical Engineering, University of Arkansas, 125 Engineering 
      Hall, Fayetteville, AR, 72701, USA.
FAU - Wolchok, Jeffrey
AU  - Wolchok J
AUID- ORCID: 0000-0003-0375-4804
AD  - Department of Biomedical Engineering, University of Arkansas, 125 Engineering 
      Hall, Fayetteville, AR, 72701, USA. jwolchok@uark.edu.
LA  - eng
GR  - CMMI-1404716/National Science Foundation/
PT  - Journal Article
DEP - 20190131
PL  - United States
TA  - Ann Biomed Eng
JT  - Annals of biomedical engineering
JID - 0361512
RN  - 0 (Extracellular Matrix Proteins)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/*metabolism
MH  - *Bioreactors
MH  - *Cell Culture Techniques
MH  - Cells, Cultured
MH  - Extracellular Matrix/*metabolism
MH  - Extracellular Matrix Proteins/*biosynthesis
MH  - *Gene Expression Regulation
MH  - Rats
OTO - NOTNLM
OT  - Central nervous system
OT  - Glial cells
OT  - Mechanobiology
OT  - Nervous system
EDAT- 2019/02/02 06:00
MHDA- 2019/06/27 06:00
CRDT- 2019/02/02 06:00
PHST- 2018/09/12 00:00 [received]
PHST- 2019/01/24 00:00 [accepted]
PHST- 2019/02/02 06:00 [pubmed]
PHST- 2019/06/27 06:00 [medline]
PHST- 2019/02/02 06:00 [entrez]
AID - 10.1007/s10439-019-02219-y [pii]
AID - 10.1007/s10439-019-02219-y [doi]
PST - ppublish
SO  - Ann Biomed Eng. 2019 Apr;47(4):967-979. doi: 10.1007/s10439-019-02219-y. Epub 
      2019 Jan 31.