Astrogliosis in a dish

Substrate stiffness induces astrogliosis in primary rat astrocytes

Christina L. Wilson, Stephen L. Hayward, Srivatsan S Kidambi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Astrogliosis due to brain injury or disease can lead to varying molecular and morphological changes in astrocytes. Magnetic resonance elastography and ultrasound have demonstrated that brain stiffness varies with age and disease state. However, there is a lack in understanding the role of varied stiffness on the progression of astrogliosis highlighting a critical need to engineer in vitro models that mimic disease stages. Such models need to incorporate the dynamic changes in the brain microenvironment including the stiffness changes. In this study we developed a polydimethyl siloxane (PDMS) based platform that modeled the physiologically relevant stiffness of brain in both a healthy (200 Pa) and diseased (8000 Pa) state to investigate the effect of stiffness on astrocyte function. We observed that astrocytes grown on soft substrates displayed a consistently more quiescent phenotype while those on stiff substrates displayed an astrogliosis-like morphology. In addition to morphological changes, astrocytes cultured on stiff substrates demonstrated significant increase in other astrogliosis hallmarks-cellular proliferation and glial fibrillary acidic protein (GFAP) protein expression. Furthermore, culturing astrocytes on a stiff surface resulted in increased reactive oxygen species (ROS) production, increased super oxide dismutase activity and decreased glutamate uptake. Our platform lends itself for study of potential therapeutic strategies for brain injury focusing on the intricate brain microenvironment-astrocytes signaling pathways.

Original languageEnglish (US)
Pages (from-to)34447-34457
Number of pages11
JournalRSC Advances
Volume6
Issue number41
DOIs
StatePublished - Jan 1 2016

Fingerprint

Rats
Brain
Stiffness
Substrates
Siloxanes
Proteins
Glial Fibrillary Acidic Protein
Magnetic resonance
Astrocytes
Glutamic Acid
Reactive Oxygen Species
Ultrasonics
Engineers
Oxygen

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Astrogliosis in a dish : Substrate stiffness induces astrogliosis in primary rat astrocytes. / Wilson, Christina L.; Hayward, Stephen L.; Kidambi, Srivatsan S.

In: RSC Advances, Vol. 6, No. 41, 01.01.2016, p. 34447-34457.

Research output: Contribution to journalArticle

Wilson, Christina L. ; Hayward, Stephen L. ; Kidambi, Srivatsan S. / Astrogliosis in a dish : Substrate stiffness induces astrogliosis in primary rat astrocytes. In: RSC Advances. 2016 ; Vol. 6, No. 41. pp. 34447-34457.
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