PubMed1990
The treatment of brain edema after severe head injury remains controversial. We investigated the uptake kinetics and pharmacokinetics of glucocorticoids in rat brain after cold lesion, employing tritium-labeled dexamethasone or tritium-labeled triamcinolone acetonide (TA). The normal brain, as demonstrated on isolated cells, revealed a saturable, time-dependent uptake of dexamethasone (rate of uptake, 5 nm/mg protein/min at 37 degrees C). This clearly defined uptake is replaced by a simple diffusion like uptake after the trauma. The pharmacokinetical studies demonstrated a rapid decline of the TA concentration after a bolus injection in the brain tissue after the trauma. Within 30 min only 11% of the initial concentration could be discovered in the traumatized brain tissue. However, after a discontinuous administration of TA, a steady state was reached in the normal brain after 24 hr (0.26 micrograms TA/g). In the traumatized brain the concentration increased steadily amounting to 0.34 micrograms TA after 24 hr. The continuous infusion of TA resulted in an equal high concentration in normal brain than after the discontinuous administration. The continuous infusion of TA, however, produced the highest concentration of TA in the traumatized brain after 24 hr (0.79 micrograms TA/g) (p less than 0.05 as compared with the discontinuous injection). Our results demonstrate that the widely used discontinuous administration of steroids result in low tissue concentration, which might account partly for the low efficiency of steroids in traumatic brain edema. The continuous administration of the steroid TA increases the concentration in the traumatized tissue and might therefore be beneficial in the treatment of brain edema after severe head injury.