Temporal effects of dexamethasone on blood-to-brain and blood-to-tumor transport of 14C-alpha-aminoisobutyric acid in rat C6 glioma

We used quantitative autoradiography (QAR) to evaluate the effect of systemically administered dexamethasone on capillary permeability in brain tumors and surrounding brain. Rats bearing unilateral right hemispheric C6 gliomas were studied at one and twelve hours after 10 mg/kg of intraperitoneal dexamethasone. Capillary permeability was determined by measuring unidirectional blood-to-brain and blood-to-tumor transport of 14C-alpha aminoisobutyric acid (14C-AIB) over fifteen minutes. 14C-AIB entry into tumor, brain adjacent-to-tumor (BAT), and ipsilateral and contralateral cortices was determined and expressed as a unidirectional transfer constant, K. Nontreated tumor K was more than two-fold greater than K for BAT and ten-fold greater than ipsilateral cortical K, confirming substantial barrier disruption in tumor. In addition, the K for BAT was also significantly greater than K for cortex, indicating that the barrier in the peritumoral region was also disrupted. One hour after dexamethasone treatment, tumor K fell to 63% of its pretreatment value (p < 0.025). By twelve hours post-treatment, tumor K fell to 25% of the untreated value (p < 0.001) and to 47% of the one-hour value (p < 0.005). BAT K fell to 29% of its untreated value (p < 0.02) and to 46% of its one-hour value (p < 0.02). By 12 hours, ipsilateral cortical K fell to 67% of the untreated cortical value (p < 0.05). Compared to untreated values, there was no significant difference between contralateral cortical K at either one or twelve hours. Capillary permeability of both C6 brain tumor and normal brain vessels around tumor are increased as measured by blood-to-tissue transport of 14C-AIB. A single dose of dexamethasone reduces capillary permeability as early as one hour after administration in the tumor, then continuously over a twelve-hour time course in both tumor and BAT.