An In Vitro Impact Model for the Study of Central Nervous System Cell Mechanobiology

作者：Heller Zachery; Wyatt Joseph; Arnaud Anna; Wolchok Jeffrey C^*

来源：Cellular and Molecular Bioengineering, 2014, 7(4): 521-531.

DOI：10.1007/s12195-014-0347-6

• Traumatic brain injury
• In vitro model
• Astrocytes
• Central nervous system

Concussive injuries are a subset of traumatic brain injuries (TBIs) during which impact of the head against another object leads to rapid deceleration and deformation of brain tissue. Mechanically triggered changes in central nervous system (CNS) cell behavior following this type of injury are believed to play a role in the pathological response to TBI observed clinically. To study the mechanobiology of CNS cells under controlled conditions an in vitro impact tester was developed to mimic the impact deceleration and strain parameters associated with concussive injuries. Similar in concept to a automotive crash test, the bench top system was capable of delivering decelerations from 0 to 300g and biaxial strains from 0 to 25% over durations from 1 to 20 ms to pure populations of cells grown in both 2d and 3d culture. The small footprint (1' x 1') and inexpensive design, utilizing many off the shelf components, makes it a useful lab based system. Utilizing the system, neuronally differentiated PC12 cells and cortical astrocytes were treated with both low (50 g + 10% stain) and high (100 g + 20%) single impact conditioning. Following both low and high impact testing, significant PC12 cell detachment was measured, suggesting as others have shown, a susceptibility of neurons to impact conditioning. Alternatively, astrocyte cultures showed no evidence of cellular detachment in response to either low or high impact conditioning, but significant reductions to the production of TGF beta 1 and MCP-1 were measured following high impact conditioning. The relationship between impact and the production of key wound healing cytokines by astrocytes not only supports astrocyte mechano-sensitivity, but also suggests their involvement in the wound healing response following TBI. We believe this device provides a unique toolset that will aid in the exploration of cellular impact mechanobiology and that ultimately an improved understanding of cell mechanobiology will help guide the development of diagnostic techniques and therapeutic interventions targeting cells with known roles in the response to TBI.

• 出版日期2014-12