Methotrexate was administered by intraperitoneal injection (100 mg/kg) to unirradiated mice, and to mice receiving varying doses of cranial irradiation.
The animals were sacrificed 24 hours after injection, and methotrexate assays were performed on brain tissue. No methotrexate was detected in the brains of the unirradiated animals. Detectable levels of methotrexate were present after 2000 rad cranial irradiation, but not after 500 rad, 1000 rad, or 1500 rad. The implications of these findings are discussed.
Cawtr 40 : 1 109-1 1 1 1, 197 7.
HE MAMMALIAN "BLOOD-BRAIN BARRIER" IS
T relatively impermeable to methotrexate, and it prevents the drug from freely passing between blood, cerebrospinal fluid, and the parenchymal tissues of the brain. '*11~12 Recently, there have been several reports in the literature documenting unexpected neurotoxicity in patients receiving systemic methotrexate and cranial irradiation, suggesting the possibility of a change in barrier function as an etiologic factor.5*6***BThe purpose of this investigation was to determine if the permeability of the blood-brain barrier to methotrexate can be altered by cranial irradiation.
Methods
Six-to-10-week-old female BALB/c mice were selected for these experiments. Irradiation was accomplished under sodium pentobarbital anesthesia (60 rcg/g) through a single posterior field encompassing the entire head and upper cervical spine. A G.E. Maxitron 250 X-ray ma-