Acceleration of the head produces a deformation of the neural and vascular components of the brain. Previous work indicates that the vasculature responds to dynamic deformation by vasoconstriction. This work and other work showing that there is an increase in intracranial pressure after traumatic head injury suggest that a venous constriction can produce regional cerebral hypoxic ischemia. Dynamic mechanical deformation of isolated neural cells results in increases in intracellular calcium concentration. The magnitude of the transient rise in concentration and therefore the rate of return of the concentration to normal depend on the magnitude and time course of the deformation. In a hypoxic ischemic environment, increases in intracellular calcium concentration that are slightly injurious are hypothesized to become more injurious.
An in vitro model of isolated neural cells is employed to determine the effect of hypoxic ischemia on the recovery of neural cells from mechanical insult. The model is composed of a neuroblastoma x glioma cell hybrid (NG108-15), which is grown in a chamber designed to deliver a known strain and strain rate to the cell while the chemical environment (of the cell) is independently controlled. The actual cell deformation is determined in the form of the average strain in the cell membrane using fluorescent microspheres. To produce hypoxic ischernia, the normal bathing media is replaced with media containing 2-deoxyglucose (25 mM) and salicylate (3 mM). The intracellular concentration of calcium is used as an index of cell injury and is measured fluorimenically in real time using a calcium indicator dye.
The responses of cells to mechanical stimulus with and without hypoxic ischemia are compared. Experiments were performed in which the cells were exposed to mechanical deformation only, hypoxic ischemia only, and the combination. These data will be used to improve injury tolerance criteria by relating the response of single cells to mechanical insults and the effects of systemic responses such as hypoxic ischemia.