The effect of steroids on gentamicin delivery to brain after blood-brain barrier disruption

Neuwelt, Edward A.; Horaczek, Alfred; Pagel, Michael A.

doi:10.3171/jns.1990.72.1.0123

Cited by 8 publications

(1 citation statement)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain scans in human glioma patients have demonstrated that dexamethasone decreases contrast enhancement and uptake of radioisotopes into brain tumors (Hatam et al, 1983;Jarden et al, 1989;Yeung et al, 1993). In non-tumor-bearing rats, reductions in the concentration of markers have also been noted in several different brain regions (Neuwelt et al, 1990;Ziylan et al, 1988). Moreover, several studies using rodent models of glioma have shown that dexamethasone signi cantly decreases uptake of radiolabeled markers (Matsukado et al, 1997;Neuwelt et al, 1982;Shapiro et al, 1990) and the extravasation of proteins and dyes into tumors (Guerin et al, 1992;Neuwelt et al, 1993;Reichman et al, 1986).…”

mentioning

confidence: 99%

Cereport® (RMP-7) increases carboplatin levels in brain tumors after pretreatment with dexamethasone

et al. 1999

View full text Add to dashboard Cite

Accumulating evidence suggests that dexamethasone might decrease permeability of the blood-brain tumor barrier, further limiting the delivery of agents into brain tumors. The bradykinin B2 receptor agonist, Cereport (RMP-7), selectively increases permeability of the vasculature supplying brain tumors in both animal models and humans. The present study was conducted to characterize the effects of dexamethasone on the blood-brain tumor barrier and its potential interaction with Cereport's ability to enhance penetration of radiolabeled carboplatin. Dexamethasone (1.5 mg/kg/day, twice a day) was given to RG2 glioma-bearing rats via oral gavage for 3 consecutive days. After treatment, animals received a 15-min intracarotid infusion of Cereport (4.5 micrograms/kg) and a bolus of [14C]carboplatin. The levels of [14C]carboplatin (nCi/g) in the tumor and nontumor regions were determined at 1, 14, or 24 h after the last dose of dexamethasone. Dexamethasone, alone, significantly decreased the levels of radiolabeled carboplatin permeating the tumor (19%), although there were no significant differences between any of the time points examined. Cereport administration significantly increased levels of carboplatin in the tumor, independent of whether or not dexamethasone was given (46% with and 49% without). Although the relative effects of Cereport on tumor carboplatin levels were not affected by dexamethasone, the absolute levels achieved with Cereport were modestly reduced (44 nCi/g versus 55.5 nCi/g of [14C]carboplatin, with and without dexamethasone, respectively). Thus, while the data support the use of Cereport as adjunctive therapy in the treatment of glioma patients, they also warn that the use of dexamethasone may reduce delivery of chemotherapeutic agents to brain tumors, even when special pharmacologic measures are employed to enhance delivery.

show abstract