Distribution of ICAM-1 immunoreactivity during aging in the human orbitofrontal cortex

Abstract

Neurological and psychiatric alterations during aging are associated with increased cerebrovascular disturbances and inflammatory markers such as Intercellular Adhesion Molecule-1 (ICAM-1). We investigated whether the distribution of ICAM-1 immunoreactivity (ICAM-1-I) in histological sections from the left orbitofrontal cortex (ORB) was altered during normal aging. Postmortem tissue from the ORB of nine younger (27–54 years old) and 10 older (60–86) human subjects was collected. Cryostat sections were immunostained only with antibodies to ICAM-1 or together with an antibody to glial fibrillary acidic protein (GFAP). The total area fraction of ICAM-1-I, and the fraction of vascular and extravascular ICAM-1-I were quantified in the gray matter. Furthermore, we examined the association of extravascular ICAM-1-I to GFAP immunoreactive (GFAP-IR) astrocytes. In all subjects, brain blood vessels were similarly ICAM-1 immunoreactive, and in some subjects there was a variable number of extravascular patches of ICAM-1-I. The area fraction of ICAM-1-I was 120% higher ( p < .0001) in the old subjects than in the young subjects. This increase localized mostly to the extravascular ICAM-1-I in register with GFAP-IR astrocytes. A much smaller, also age-dependent increase occurred in vascular ICAM-1-I. Our results indicate a dramatic increase in extravascular ICAM-1-I associated to GFAP-IR astrocytes in the ORB in normal aging. This increase may contribute to an enhanced risk for brain inflammatory processes during aging, although a role of extravascular ICAM-1 as a barrier to further inflammation cannot be ruled out.