Canonical NF-B signaling pathway and GRO-/CXCR2 axis are activated in unruptured intracranial aneurysm patients

Activation of the nuclear factor kappa-B (NF-kappa B) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-kappa B p65 subunit and the GRO-alpha chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-kappa B p65 concentrations were significantly lower, while median CSF GRO-alpha and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-kappa B p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-alpha concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-alpha concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-kappa B p65 and significantly increased CSF GRO-alpha and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-kappa B signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-kappa B pathway with the participation of the NF-kappa B p65 subunit and the GRO-alpha/CXCR2 axis in the formation of IA, further in vivo model studies are needed.