Discipline of Molecular and Cell Biology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):220-8. doi: 10.1016/j.ijrobp.2009.08.017.
To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR).
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.
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.
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.
确定细胞间黏附分子-1（ICAM-1）在照射后脑损伤发病机制中的作用。
我们评估了小鼠颅脑照射后大脑中 ICAM-1 的表达，并确定了 ICAM-1 基因野生型（+/+）或敲除（-/-）小鼠照射后的组织病理学和行为变化。
照射后 ICAM-1mRNA 和蛋白表达呈早期剂量依赖性增加。照射后 8 个月，ICAM-1+/+小鼠的内皮细胞和神经胶质细胞中观察到 ICAM-1 免疫反应性增加。ICAM-1-/-小鼠无表达。10-17Gy 照射后 2 个月，ICAM-1+/+和 ICAM-1-/-小鼠均出现类似的血管异常，10Gy 照射后 8 个月出现脱髓鞘和海马神经发生抑制。10Gy 后，与年龄匹配的基因型对照相比，照射后的 ICAM-1+/+和 ICAM-1-/-小鼠在 2-6 个月的旷场、明暗箱和 T 迷宫中表现出相似的行为变化。
照射后小鼠脑血管和神经胶质细胞中 ICAM-1 早期和晚期上调。然而，ICAM-1 在颅脑单次中等剂量照射后的组织病理学损伤和行为功能障碍中没有因果作用。
