Analysis of the Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Traumatic Brain and Spinal Cord Injury: Insight into Recent Advances in Actions of Neurochemokine Agents

CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its biological properties through interaction with one dedicated CX3CR1 receptor which belongs to a family of G protein-coupled receptors (GPCR). The CX3CL1/CX3CR1 axis acts in many physiological phenomena including those occurring in the central nervous system (CNS), by regulating the interactions between neurons, microglia, and immune cells. Apart from the role under physiological conditions, the CX3CL1/CX3CR1 axis was implied to have a role in different neuropathologies such as traumatic brain injury (TBI) and spinal cord injury (SCI). CNS injuries represent a serious public health problem, despite improvements in therapeutic management. To date, no effective treatment has been determined, so they constitute a leading cause of death and severe disability. The course of TBI and SCI has two consecutive poorly demarcated phases: the initial, primary injury and secondary injury. Recent evidence has implicated the role of the CX3CL1/CX3CR1 axis in neuroinflammatory processes occurring after CNS injuries. The importance of the CX3CL1/CX3CR1 axis in the pathophysiology of TBI and SCI in the context of systemic and direct local immune response is still under investigation. This paper, based on a review of the literature, updates and summarizes the current knowledge about CX3CL1/CX3CR1 axis involvement in TBI and SCI pathogenesis, indicating possible molecular and cellular mechanisms with a potential target for therapeutic intervention.