NEW IN-VITRO MODEL OF TRAUMATIC NEURONAL INJURY EVALUATION OF SECONDARY INJURY AND GLUTAMATE RECEPTOR-MEDIATED NEUROTOXICITY

The multiplicity and complexity of secondary injury processes followin g brain trauma in vivo make it difficult to elucidate the roles of spe cific injury mechanisms, As with other areas of CNS injury, such as is chemia, this has led to the development of in vitro models, Here we de scribe a new trauma model, in which standardized trauma is delivered t o neuronal/glial cultures using a special mechanical device that produ ces concentric circular cuts in the cell layer. Changes in the number of circles (from 1 to 6) allows variation of injury severity, Comparis on studies of cell death induced by such trauma in glial and neuronal/ glial cultures demonstrated that glial cells are relatively resistant to this injury, and that the cell death after trauma to neuronal/glial cultures reflects primarily neuronal death, Consistent with other in vivo and in vitro studies, glutamate receptor antagonists MK 801 and M CPG were neuroprotective, Thus, this model appears useful for studying glutamatergic mechanisms involved in secondary injury, and may prove useful for evaluating certain pharmacological strategies for CNS traum a.