1. ^*Department of Trauma Surgery, The Alfred Hospital & Monash University, Melbourne, Australia
2. ^†Institute of Pharmaceutical Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland
3. ^‡Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, Switzerland
4. ^§Novartis Institutes for BioMedical Research (NIBR), Neuroscience Research, Novartis Pharma AG, Basel, Switzerland

Correspondence: Mario Rancan, Department of Trauma Surgery, The Alfred Hospital & Monash University, Commercial Road, Melbourne, VIC 3004, Australia; e-mail: RancanMario@hotmail.com

Received 18 January 2004; Revised 25 March 2004; Accepted 19 April 2004.

Abstract

The potential role of the chemokine Fractalkine (CX₃CL1) in the pathophysiology of traumatic brain injury (TBI) was investigated in patients with head trauma and in mice after experimental cortical contusion. In control individuals, soluble (s)Fractalkine was present at low concentrations in cerebrospinal fluid (CSF) (12.6 to 57.3 pg/mL) but at much higher levels in serum (21,288 to 74,548 pg/mL). Elevation of sFractalkine in CSF of TBI patients was observed during the whole study period (means: 29.92 to 535.33 pg/mL), whereas serum levels remained within normal ranges (means: 3,100 to 59,159 pg/mL). Based on these differences, a possible passage of sFractalkine from blood to CSF was supported by the strong correlation between blood–brain barrier dysfunction (according to the CSF-/serum-albumin quotient) and sFractalkine concentrations in CSF (R = 0.706; P < 0.01). In the brain of mice subjected to closed head injury, neither Fractalkine protein nor mRNA were found to be augmented; however, Fractalkine receptor (CX₃CR1) mRNA steadily increased peaking at 1 week postinjury (P < 0.05, one-way analysis of variance). This possibly implies the receptor to be the key factor determining the action of constitutively expressed Fractalkine. Altogether, these data suggest that the Fractalkine-CX₃CR1 protein system may be involved in the inflammatory response to TBI, particularly for the accumulation of leukocytes in the injured parenchyma.