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 less than 0.025). By twelve hours post-treatment, tumor K fell to 25% of the untreated value (p less than 0.001) and to 47% of the one-hour value (p less than 0.005). BAT K fell to 29% of its untreated value (p less than 0.02) and to 46% of its one-hour value (p less than 0.02). By 12 hours, ipsilateral cortical K fell to 67% of the untreated cortical value (p less than 0.05). Compared to untreated values, there was no significant difference between contralateral cortical K at either one or twelve hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Shapiro
W R
WR
George C. Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Hiesiger
E M
EM
Cooney
G A
GA
Basler
G A
GA
Lipschutz
L E
LE
Posner
J B
JB
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000098:blood supply*; D002199:Capillary Permeability / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D005910:Glioma / Q000098:blood supply*; D051381:Rats
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D003907:Dexamethasone