TY - JOUR
T1 - A device to study the initiation and propagation of calcium transients in cultured neurons after mechanical stretch
AU - Lusardi, Theresa A.
AU - Rangan, Jeff
AU - Sun, David
AU - Smith, Douglas H.
AU - Meaney, David F.
N1 - Funding Information:
The work presented here was funded by NIH NICHD 41699, NINDS RO1 35712, and NIH NINDS P01 NS08803.
PY - 2004/11
Y1 - 2004/11
N2 - The brain is generally considered protected from mechanical forces. However, during traumatic events, cells in brain tissue are exposed to complex mechanical events including transient acceleration, pressure, and direct stretch, This paper presents a model to expose cultured cells of the central nervous system (CNS) to a defined stretch insult. The system is designed to apply a single transient uniaxial stretch to cultured cells; control of both the magnitude and rate of stretch allows study of a broad range of conditions, from physiologic to traumatic. Distinct from previous cell-stretching systems, we control the fraction of cells deformed and examine the response of stretched cells or the surrounding population of unstretched cells, the "mechanical penumbra," of the same culture. Finally, we use this new model with cultured neurons, measuring the acute calcium response in traumatically stretched cells and the propagation of this calcium influx in neighboring, but unstretched cells. Stretched neurons exhibit a strain rate and magnitude-dependent response, unstretched exhibit an "all-or-none" response. This model will further our understanding of the complex interaction between mechanical stimuli, resulting biochemical cascades, and interaction between mechanical and other challenges, thereby furthering our understanding of the initiation and evolution of cellular damage following traumatic CNS injury.
AB - The brain is generally considered protected from mechanical forces. However, during traumatic events, cells in brain tissue are exposed to complex mechanical events including transient acceleration, pressure, and direct stretch, This paper presents a model to expose cultured cells of the central nervous system (CNS) to a defined stretch insult. The system is designed to apply a single transient uniaxial stretch to cultured cells; control of both the magnitude and rate of stretch allows study of a broad range of conditions, from physiologic to traumatic. Distinct from previous cell-stretching systems, we control the fraction of cells deformed and examine the response of stretched cells or the surrounding population of unstretched cells, the "mechanical penumbra," of the same culture. Finally, we use this new model with cultured neurons, measuring the acute calcium response in traumatically stretched cells and the propagation of this calcium influx in neighboring, but unstretched cells. Stretched neurons exhibit a strain rate and magnitude-dependent response, unstretched exhibit an "all-or-none" response. This model will further our understanding of the complex interaction between mechanical stimuli, resulting biochemical cascades, and interaction between mechanical and other challenges, thereby furthering our understanding of the initiation and evolution of cellular damage following traumatic CNS injury.
KW - CNS trauma
KW - Fura-2
KW - In vitro model
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U2 - 10.1114/B:ABME.0000049038.75368.75
DO - 10.1114/B:ABME.0000049038.75368.75
M3 - Article
C2 - 15636114
AN - SCOPUS:11044239390
SN - 0090-6964
VL - 32
SP - 1546
EP - 1559
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
IS - 11
ER -