ABSTRACT
As in the periphery, the accumulation of circulating immune cells within the cerebrovasculature is facilitated by the upregulation of endothelial cell surface adhesion molecules [1]. In AD brain, upregulation of endothelial vascular cell adhesion molecule-1 (VCAM-1) [19] and intercellular adhesion molecule-1 (ICAM-1) [20-22] has been reported, and this upregulation is localized to areas of the cerebrovasculature that are in close proximity to Aβ deposits. Similar changes in cerebrovascular adhesion molecule expression reported for other central nervous system disorders have been linked to disease progression. Increases in vascular P-selectin, VCAM-1, and ICAM-1 are associated with demyelinating lesions of multiple sclerosis [2, 3]. These adhesion molecules define early stages of lesion formation [1], and the resulting early accumulation of monocytes correlates with subsequent demyelination [2]. Accordingly, the success of corticosteroid therapy in multiple sclerosis has been ascribed, in part, to its ability to regulate endothelial adhesion molecule expression [2]. Elevated expression of vascular adhesion molecules, including P-selectin, E-selectin, VCAM-1, and ICAM-1, observed following ischemic stroke facilitates the recruitment of leukocytes, which are proposed to contribute to post-ischemic injury [1, 4-6]. As such, anti-adhesion therapies reduce infarct volume in animal models [4-6, 23]. ICAM-1 is upregulated within the brain microvasculature of cerebral malaria patients and animal models of the disease [7-9]. It also colocalizes with the sequestration of infected erythrocytes [8, 9], whereas administration of anti-ICAM-1 releases sequestered erythrocytes [9]. In addition, genetic mutations within ICAM-1 correlate with susceptibility to cerebral malaria [9]. Increased levels of expression of VCAM-1 and E-selectin are found in the brains of patients with HIV-associated dementia [10] and facilitate the passage of infected monocytes across the BBB to contribute to brain infection and dementia [10, 11].
