Traumatic brain injury (TBI) is an important but poorly understood cause of lifelong disability in the United States. Progress has been made in animate models of TBI, showing a clear relationship between the type and magnitude of injury and the histologic and behavioral outcomes, it is still not clear whether TBI-related pathologies are independent of similar stroke-related pathologies. The brain is generally considered protected from mechanical forces. However, during traumatic events, cells in the brain tissue are exposed to a complex set of mechanical forces that include transient acceleration, pressure, and direct stretch. This dissertation presents a model to expose cultured cells of the central nervous system (CNS) to a defined stretch insult and to monitor both the acute and delayed response of neurons to the stretch. The system is designed to apply a controlled, transient mechanical stretch to cultured cells, ranging from physiologic to traumatic. A fraction of the culture was deformed, allowing examination of the response of either stretched or unstretched cells in the same culture. Together, this system allows us to monitor the biochemical progression of the mechanically-induced changes in the cultured CNS cells.

Acute changes in [Ca²⁺]_i caused by a rapid stretch of cultured hippocampal neurons showed increases in [Ca²⁺]_i correlated with the level of mechanical insult, and that the magnitude of the peak calcium influx exceeded levels initiated by NMDA or glutamate exposure. Despite this acute increase in [Ca²⁺]_i, cell viability 24 hours following stretchinjury was unaffected for all but the most severely stretch-injured cultures. Likewise, in adjacent unstretched neurons, increases in intracellular calcium were also found in the acute period after stretch, but no viability change was observed in these neurons 24 hours after stretch. Consistent with previous studies, inhibition of the cytosolic calcium transient in neurons by calcium free media or MK-801 resulted in protection from NMDA neurotoxicity. In contrast, these treatments did not improve viability following mechanical stretch-injury. These data suggest that an acute increase in [Ca²⁺]_i may not be a primary modulator of neuron death following mechanical deformation of neurons.