Acute changes in blood-CSF barrier permselectivity to serum proteins after intrathecal methotrexate and CNS irradiation.
Ten children affected by acute lymphoblastic leukaemia without CNS involvement were treated with a CNS prophylaxis protocol. Intrathecal methotrexate and CNS irradiation (60Co) administered at different times both induced an increase in blood-CSF barrier permeability to serum proteins (albumin, IgG, alpha 2 macroglobulin). The relationship between permeability coefficients of proteins was analysed by theoretical porous or vesicular blood-CSF barrier models. The analysis indicated that both therapeutic procedures affect endothelial pinocytosis. An increase in radius of pinocytotic vesicles from 400 to 1500 A seemed the most relevant change. The damage of endothelial barrier permselectivity could be involved in acute and late delayed toxic effects of intrathecal methotrexate and of CNS irradiation.
D000208:Acute Disease; D001798:Blood Proteins / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000528:radiation effects; D002490:Central Nervous System / Q000528:radiation effects*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D006801:Humans; D007278:Injections, Spinal; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000532:radiotherapy; D008727:Methotrexate / Q000627:therapeutic use*; D008954:Models, Biological
D001798:Blood Proteins; D008727:Methotrexate