CORTICOTROPIN-RELEASING FACTOR DECREASES VASOGENIC BRAIN EDEMA

We report the first series of studies comparing the anti-edematous eff ects of human corticotropin-releasing factor (hCRF) and dexamethasone in an experimental model of vasogenic peritumoral brain edema, Both hC RF and dexamethasone effectively decreased blood-brain barrier (BBB) p ermeability of intracerebral RG2 gliomas in rats as observed by contra st-enhanced T-1-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 ED(50) for hCRF was 59 mu g/k g s.c. twice a day, and that for dexamethasone was 0.61 mg/kg i.m. twi ce a day; the hCRF:dexamethasone dose-potency ratio was 120:1 on a mol ar basis. The anti-edematous action of hCRF is not mediated by the rel ease of adrenal corticosteroids. A direct action of hCRF on the tumor microvasculature results in restoration of BBB integrity and up-regula tion of BBB-specific protein expression. The average survival time wit h chronic treatment was prolonged significantly in the hCRF-treated gr oup (35 days) compared with the dexamethosone-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 substan tial benefits with respect to reducing the major side effects encounte red with long-term, high-dose corticosteroid treatment.