Cell adhesion molecules in traumatic brain injury: Orchestrating leukocyte infiltration, BBB disruption, and neuroinflammation.

Cell adhesion molecules (CAMs) are essential regulators of tissue architecture, inflammation, and cellular signaling, mediating interactions between cells and their microenvironment. Major CAM families include intercellular adhesion molecules (ICAMs), vascular cell adhesion molecules (VCAMs), platelet endothelial cell adhesion molecules (PECAMs), and selectins. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are expressed on activated endothelial cells and promote firm leukocyte adhesion through interactions with integrins such as lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) and macrophage-1 antigen (CD11b/CD18). Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) facilitates leukocyte transmigration across endothelial junctions. P-selectin (platelet selectin) and E-selectin (endothelial selectin) mediate the initial rolling of leukocytes via binding to P-selectin glycoprotein ligand-1 (PSGL-1). In traumatic brain injury (TBI), endothelial activation and blood-brain barrier (BBB) disruption upregulates these adhesion molecules, promoting leukocyte recruitment and infiltration into the injured brain. This process amplifies neuroinflammation through the release of cytokines, chemokines, and reactive oxygen species, contributing to oxidative stress, mitochondrial dysfunction, and neurodegeneration. In this review, we highlight the roles of ICAM-1, VCAM-1, PECAM-1, and selectins in TBI pathogenesis, with particular emphasis on ICAM-1-mediated leukocyte transmigration.