How can mechanical forces regulate cell death pathways in the brain?

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We have continued to look at cellular mechanics questions, but now with an important twist. We want to measure the variation of strains experienced by cells of the cortex and hippocampus, since these cells commonly undergo some form of cell death after traumatic injury. Mike DeRidder is measuring how cells in slices of brain tissue move (see figure on right) and displace when the tissue is deformed. We use slices of tissue, rather than whole brain preparations, because this will allow us to track precisely the motion of the cells in near-real time. See video at bottom of page to understand the shape and distribution of cells throughout the brain slice

Mike is interested in understanding how to predict the local strain fields surrounding individual neurons, and how these will correspond to the pattern of cell death that occurs in these slice cultures. In the literature, it is known that two forms of cell death - uncontrolled necrosis and a more controlled apoptotic death - occur in traumatic brain injury. If we find, for example, that apoptotic cell death occurs at lower strains than necrotic death, this will highlight the importance of examining apoptotic cell death pathways in mild brain injuries such as concussion. If, on the other hand, these two forms of cell death occur under the same general mechanical conditions, then a more complex treatment will be necessary. A recent summary of Mike's work can be found by clicking on this link.

To understand how cells in brain tissue are mechanically coupled to each other, we label cells in a slice of brain tissue and image the labelled cells using a confocal microscope. With this microscope, we can scan and image cells at different planes throughout the slice. Watch the QuickTime video as the imaging plane moves vertically through the brain slice. Living cells are loaded with a green flourescent dye, while dead cells are labelled with a red floursecent dye. Watch it play continuously or use the play and pause commands below the image to scan through the images of cells as you scan from the bottom to the top of the slice.
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Mike's project has an interesting dimension. Namely, he would like to see if these cell death processes act in parallel with the formation of new cells within the injured brain. In addition, he is interested if the addition of exogenous growth factors (for example, brain derived neurotrophic factor, nerve growth factor) will affect the formation of new cells in the injured slice culture, perhaps outnumbering the number of dying cells. Some of these growth factors have a preference for directing undifferentiated cells into neurons; this could be a method to understand if such a controlled response could be possible within the injured brain.