[Time course of the cerebroprotective effect of dexamethasone in experimental head injury]

Despite the widespread use of glucocorticoids in patients with severe head injury, the usefulness is still controversial. In the past, the effect was investigated only in terms of dose-response relationship. We have, however, studied the time factor for the administration of dexamethasone to obtain maximal beneficial effect together with investigating the influence of actinomycin-D, an inhibitor of messenger RNA synthesis, before dexamethasone treatment. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 g dropped from a height of 17.8 cm above the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in about 70% and death in about 30% of animals. The severity of consciousness disturbance was evaluated by a pair of indices in time interval: time required for the recovery of righting reflex (RR) and for the recovery of spontaneous movement (SM). 4 mg/kg of dexamethasone phosphate was given intraperitoneally 0.5, 4, 6, 12, 18 or 24 hours before injury. Actinomycin-D of 0.5 mg/kg was injected intravenously 1 h before each dexamethasone treatment in separate animals. In the other group of animals, dose was changed with varying time course of dexamethasone pretreatment, e.g., 2, 4, 6 or 8 mg/kg given 0.5, 2 or 4 h before injury. It was found that dexamethasone of 4 mg/kg pretreatment 4-12 hours significantly improved the recovery from consciousness disturbance and death rate. Actinomycin-D given before dexamethasone treatment completely abolished the protective effect of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)