An additional and straightforward technique to use on cultures is to mechanically compress the cultures with a weight, akin to the weight drop method developed initially by Allen (1911) to study spinal cord injury in vivo. Indeed, one of the first in vitro models for central nervous system (CNS) injury used this technique of spinal cord cultures (Balentine et al., 1988). The technique is well suited to organotypic cultures that have a defined thickness and more realistic 3D architecture, and can be used to study the effects of both mechanical injury and a superimposed hypoxic injury (Adamchik et al., 2000). The order of the injuries can be changed, so that the mechanical injury can be considered the secondary injury, or vice versa. The technique to compress the tissue construct can also change; a dropped weight can be replaced by a rolling stainless steel bar, or a composite foam indentor over a region of the culture (Adamchik et al., 2000). Recently, this type of model showed the potential spreading depression that can occur from mechanical injury (Church and Andrew, 2005). One primary disadvantage of this technique, though, is drawing the direct in vivo correlate for this method. Crush injuries to the brain parenchyma are rare, and are complicated by overlying skull fracture.
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