This project is aimed at identifying fundamental features of traumatic cerebral edema and testing therapeutic measures for its control. The experimental model used involves impact to the skull plus change in velocity of the head, the two events that are considered essential mechanisms for cerebral injury in human head trauma. Recent results have suggested that inter-active pathophysiologic events occur in white matter neighboring tissue hemorrhage that include vasogenic edema, severe lactic acidosis and decreases in high energy phosphate concentrations. We hypothesize that the sequence of events leading to severe energy perturbation of the white matter includes decreases in white matter blood flow that are exaggerated with the addition of vasogenic edema. To test this hypothesis, and to further characterize the acute pathophysiology of blunt head injury, we will examine and correlate, in the same head-injured cats: 1) the topography and time course of regional cerebral blood flow, using radioactive microsphere and hydrogen clearance methods; 2) regional cerebral metabolite concentrations, using enzymatic fluorometric techniques; 3) location of accumulation of protein-rich edema fluid, using density measurements. Thereapy studies will also be conducted to evaluate the effects of attenuation of two important pathophysiologic events observed in our model: vasogenic edema and severe lactic acidosis. Mannitol, an agent commonly used to reduce edema in human head injury, and tromethamine, an agent suggested to relieve cerebral lactic acidosis, will be administered separately and measured for effects on: arterial and intracranial pressures; regional white matter metabolite concentrations, blood flow (using the hydrogen clearance technique), magnitude and territory of edema, and blood volume; and, for the tromethamine study, white matter pH. These studies are designed to: 1) add valuable information concerning the acute pathophysiology of blunt craniocerebral trauma; and 2) determine the effects of two clinically-relevant therapeutic agents on physiologic and biochemical variables in the mechanically-injured brain.
| Dimlich, R V; Tornheim, P A; Kindel, R M et al. (1990) Effects of a 21-aminosteroid (U-74006F) on cerebral metabolites and edema after severe experimental head trauma. Adv Neurol 52:365-75 |
| Tornheim, P A; McDermott, F; Shiguma, M (1990) Effect of experimental blunt head injury on acute regional cerebral blood flow and edema. Adv Neurol 52:377-84 |
| Clark Jr, L C; Spokane, R B; Hoffmann, R E et al. (1989) The nature of fluorocarbon enhanced cerebral oxygen transport. Adv Exp Med Biol 248:341-55 |
| Wagner, K R; Tornheim, P A; Eichhold, M K (1985) Acute changes in regional cerebral metabolite values following experimental blunt head trauma. J Neurosurg 63:88-96 |
| Tornheim, P A; Yi, L F; Wagner, K L et al. (1985) Acute responses to experimental blunt head trauma: topography of white matter edema. Brain Res 337:81-90 |
