Immunohistohemical expression of the chemokine fractalkine and its receptor in the human brain cortex after severe traumatic brain injury and brain hemorrhage

J Neurosurg Sci. 2013 Mar;57(1):55-62.

Abstract

Aim: Recent experimental studies have suggested that chemokines, a subclass of chemoattractant cytokines which play an important role in regulating leukocyte migration and intercellular communication, participate in brain responses of traumatic injury. Fractalkine (CX3CL1) is a peculiar chemokine, the only one with a CX3C motif, existing both as a soluble and a membrane-anchored molecule. In the brain, Fractalkine has been suggested to have a role in neuroprotection under experimental conditions of brain injury.

Methods: Eighteen human brain samples were obtained during surgery of decompressive craniotomy for severe traumatic brain injury (TBI) or after spontaneous intracranial haemorrhage (ICH). Five normal brain samples were obtained during surgery for unruptured intracranial aneurysms (standard gyrectomy). Immunohistochemistry of formalin fixed and paraffin embedded tissues was performed in order to verify the expression of fractalkine and its receptor (CX3CR1). The values of chemokine and receptor expression were correlated with the clinical parameters of the patients.

Results: The chemokine fractalkine was significantly upregulated in the neural compartment after brain injury, compared to normal brain samples. Intensity scores were significantly higher when the interval between injury and surgery was >5 h, (P=0.015). In the glial compartment, Fractalkine expression was significantly associated with less severe clinical conditions and lower intracranial pressure at surgery (P=0.014). Expression of the receptor CX3CR1 was detected, at low intensity, on both glial and neurons. Higher expression in neurons was associated with better clinical conditions (Glasgow score) of patients at admission (P=0.037).

Conclusion: The results of this study highlights for the first time that fractalkine and its receptor CX3CR1 are expressed in the human brain after TBI and ICH and may be involved in the limitation of tissue damage.

MeSH terms

  • Adult
  • Aged
  • Brain Injuries / immunology
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • CX3C Chemokine Receptor 1
  • Chemokine CX3CL1 / immunology
  • Chemokine CX3CL1 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Intracranial Hemorrhages / immunology
  • Intracranial Hemorrhages / metabolism*
  • Intracranial Hemorrhages / pathology
  • Male
  • Middle Aged
  • Neuroglia / immunology
  • Neuroglia / metabolism
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / metabolism*
  • Severity of Illness Index*
  • Time Factors
  • Young Adult

Substances

  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Chemokine CX3CL1
  • Receptors, Chemokine