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Release of the neuronal glycoprotein ICAM‐5 in serum after hypoxic‐ischemic injury
Author(s) -
Guo Huang,
Tong Ning,
Turner Terence,
Epstein Leon G.,
McDermott Michael P.,
Kilgan Patrick
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200010)48:4<590::aid-ana5>3.0.co;2-7
Subject(s) - icam 1 , microglia , lipopolysaccharide , intercellular adhesion molecule 1 , hippocampal formation , endocrinology , medicine , biology , cell adhesion molecule , immunology , inflammation
Intercellular adhesion molecule (ICAM)‐5 (telencephalin) is unique among the ICAMs, because it is only expressed in somatodendritic membranes of telencephalic neurons. To investigate the fate of ICAM‐5 during focal brain injury, we induced hypoxia‐ischemia (HI) damage in adult mice by right common carotid artery ligation followed by hypoxia. ICAM‐5 was detectable in serum within a 48‐hour window after HI injury. In HI brain, dendritic ICAM‐5 immunoreactivity was abolished, but it was present in the neuropil and soma of hippocampal pyramidal, dentate granule, and some cortical and striatal neurons. After HI injury, levels of ICAM‐5 protein and messenger RNA initially increased, and ICAM‐5 messenger RNA expression then decreased, although protein levels continued to increase. Because HI injury induces microglial activation with increases in CD11a/CD18 (lymphocyte function antigen [LFA]‐1) counterreceptors to ICAM‐5, we investigated whether modulation of interactions between LFA‐1 receptors and brain ICAM‐5 during HI injury are associated with changes in levels of serum ICAM‐5. Intracerebroventricular administration of lipopolysaccharide to activate microglia before HI injury resulted in elevated serum ICAM‐5 levels compared with those in mice with only HI injury. Pretreatment with anti‐LFA‐1 antibodies before HI injury or LFA‐1 receptor knockout mice with HI injury had markedly reduced levels of serum ICAM‐5. Lipopolysaccharide levels increased, whereas LFA‐1 receptor blockade or LFA‐1 knockout decreased HI injury in the first 12 hours. These data suggest that during the necrotic phase of HI injury, serum ICAM‐5 may be a potential marker for somatodendritic neuronal damage. Ann Neurol 2000;48:590–602