| Abstract: |
We report the first series of studies comparing the anti-edematous effects of human corticotropin-releasing factor (hCRF) and dexamethasone in an experimental model of vasogenic peritumoral brain edema. Both hCRF and dexamethasone effectively decreased blood-brain barrier (BBB) permeability of intracerebral RG2 gliomas in rats as observed by contrast-enhanced T1- weighted magnetic resonance imaging. A decrease in the water content of tumor and peritumoral brain tissue was observed with proton-density magnetic resonance imaging and confirmed by direct wet/dry tissue measurements. The calculated ED50 for hCRF was 59 μg/kg s.c. twice a day, and that for dexamethasone was 0.61 mg/kg i.m. twice a day: the hCRF:dexamethasone dose- potency ratio was 120:1 on a molar basis. The anti-edematous action of hCRF is not mediated by the release of adrenal corticosteroids. A direct action of hCRF on the tumor microvasculature results in restoration of BBB integrity and up-regulation of BBB-specific protein expression. The average survival time with chronic treatment was prolonged significantly in the hCRF-treated group (35 days) compared with the dexamethasone-treated group (28 days; P < 0.05) and the saline-treated control group (22 days; P < 0.0001). hCRF, as an alternative to corticosteroid therapy, may provide substantial benefits with respect to reducing the major side effects encountered with long-term, high- dose corticosteroid treatment. |
