Release of the neuronal glycoprotein ICAM-5 in serum after hypoxic-ischemic injury

Intercellular adhesion molecule (ICAM)-5 (telencephalin) is unique among th e ICAMs, because it is only expressed in somatodendritic membranes of telen cephalic neurons. To investigate the fate of ICAM-5 during focal brain inju ry, we induced hypoxia-ischemia (HI) damage in adult mice by right common c arotid 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 immu noreactivity was abolished, but it was present in the neuropil and soma of hippocampal pyramidal, dentate granule, and some cortical and striatal neur ons. After HI injury, levels of ICAM-5 protein and messenger RNA initially increased, and ICAM-5 messenger RNA expression then decreased, although pro tein levels continued to increase. Because HI injury induces microglial act ivation with increases in CD11a/CD18 (lymphocyte function antigen [LFA]-1) counterreceptors to ICAM-5, we investigated whether modulation of interacti ons between LFA-1 receptors and brain ICAM-5 during HI injury are associate d with changes in levels of serum ICAM-5. Intracerebroventricular administr ation of lipopolysaccharide to activate microglia before HI injury resulted in elevated serum ICAM-5 levels compared with those in mice with only HI i njury. Pretreatment with anti-LFA-l antibodies before HI injury or LFA-1 re ceptor knockout mice with HI injury had markedly reduced levels of serum IC AM-5. Lipopolysaccharide levels increased, whereas LFA-1 receptor blockade or LFA-1 knockout decreased HI injury in the first 12 hours. These data sug gest that during the necrotic phase of HI injury, serum ICAM-5 may be a pot ential marker for somatodendritic neuronal damage.