Radiation-induced permeability and leukocyte adhesion in the rat blood-brain barrier: modulation with anti-ICAM-1 antibodies.
We assessed the acute effects of radiation on the rat blood-brain barrier. A cranial window model and intravital microscopy were used to measure changes in permeability and leukocyte adhesion in pial vessels after a localized, single dose of 20 Gy. Permeability was assessed using five sizes of fluorescein isothiocyanate (FITC)-dextran molecules (4.4-, 10-, 38.2-, 70-, and 150-kDa) with measurements performed before and 2, 24, 48, 72 and 96 h after irradiation for the 4.4 and 38.2-kDa molecules and before and 24 h after irradiation for the other three molecules. To demonstrate the nature of blood-brain barrier permeability, we concurrently studied the permeability of microvessels in the cremaster muscle. In both tissues, permeability to FITC-dextran was significantly greater 24 h after irradiation than before (P<0.05). The exception was that radiation did not affect the permeability of pial vessels to the 150-kDa molecule. The particle-size dependence of the permeability changes in the brain were indicative of altered integrity of endothelial tight junctions and occurred concomitantly with an increase in cell adhesion which was determined by fluorescent labeling of leukocytes with rhodamine 6G. An early inflammatory response to irradiation was apparent in the brain 2 h after irradiation. The numbers of rolling and adherent leukocytes increased significantly and peaked at 24 h. Injection with the anti-ICAM-1 mAb significantly reduced leukocyte adhesion and permeability thereby linking the two processes. These findings provide a target to reduce radiation-related permeability and cell adhesion and potentially the side effects of radiation in the CNS.
Yuan
Hong
H
Department of Radiation Oncology, Mail Stop 220, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105-2794, USA.
Gaber
M Waleed
MW
McColgan
Tamara
T
Naimark
Michael D
MD
Kiani
Mohammad F
MF
Merchant
Thomas E
TE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000528:radiation effects*; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000528:radiation effects*; D002199:Capillary Permeability / Q000187:drug effects / Q000528:radiation effects*; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D036904:Leukocyte Rolling / Q000187:drug effects / Q000528:radiation effects; D007962:Leukocytes / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D018799:Intercellular Adhesion Molecule-1; D016650:Fluorescein-5-isothiocyanate