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.