Role of intercellular adhesion molecule-1 in radiation-induced brain injury.
OBJECTIVE
To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR).


METHODS
We assessed the expression of ICAM-1 in mouse brain after cranial IR and determined the histopathologic and behavioral changes in mice that were either wildtype (+/+) or knockout (-/-) of the ICAM-1 gene after IR.


RESULTS
There was an early dose-dependent increase in ICAM-1 mRNA and protein expression after IR. Increased ICAM-1 immunoreactivity was observed in endothelia and glia of ICAM-1+/+ mice up to 8 months after IR. ICAM-1-/- mice showed no expression. ICAM-1+/+ and ICAM-1-/- mice showed similar vascular abnormalities at 2 months after 10-17 Gy, and there was evidence for demyelination and inhibition of hippocampal neurogenesis at 8 months after 10 Gy. After 10 Gy, irradiated ICAM-1+/+ and ICAM-1-/- mice showed similar behavioral changes at 2-6 months in open field, light-dark chamber, and T-maze compared with age-matched genotype controls.


CONCLUSIONS
There is early and late upregulation of ICAM-1 in the vasculature and glia of mouse brain after IR. ICAM-1, however, does not have a causative role in the histopathologic injury and behavioral dysfunction after moderate single doses of cranial IR.
Wu
Kai-Liang
KL
Discipline of Molecular and Cell Biology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Tu
Ba
B
Li
Yu-Qing
YQ
Wong
C Shun
CS
D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D016371:Cranial Irradiation; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000378:metabolism / Q000528:radiation effects; D006624:Hippocampus / Q000473:pathology / Q000528:radiation effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D018782:Maze Learning / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000528:radiation effects; D055495:Neurogenesis / Q000502:physiology / Q000528:radiation effects; D009457:Neuroglia / Q000378:metabolism / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism*
D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1