Activation of Nuclear Factor κB in Cerebral Arteriovenous Malformations

BACKGROUND: Cerebral arteriovenous malformations (AVMs) do not seem to be static congenital vascular malformations, but rather are dynamically changing pathologies. It is well-known from clinical situations that these AVMs can enlarge or shrink. Nuclear factor kappa B (NF-kappa B) is a nuclear transcription factor that regulates a number of physiological processes, such as inflammation, apoptosis, and cellular growth. OBJECTIVE: To analyze phosphorylation of NF-kappa B and related molecules in cerebral AVM specimens. METHODS: We examined 19 specimens of cerebral AVMs from 18 patients. Immunohistochemical analysis was performed using an NF-kappa B p65 (C22B4) rabbit monoclonal antibody, the phosphorylated form of NF-kappa B (PNF-kappa B) p65 (Ser276) rabbit antibody, and an I kappa B alpha mouse monoclonal antibody. RESULTS: Expression of NF-kappa B was mainly confined to the endothelial lining and the infiltrating inflammatory cells in the perivascular regions. PNF-kappa B showed the highest level of expression in both endothelial cells and perivascular infiltrating cells. PNF-kappa B was intensely expressed in the endothelium and perivascular infiltrating cells of 15 specimens (78.9%). NF-kappa B and I kappa B were also expressed in endothelial cells and perivascular infiltrating inflammatory cells, but at lower levels than PNF-kappa B. Immunohistochemical studies revealed that PNF-kappa B was mainly concentrated in the nuclei of endothelial and infiltrating inflammatory cells. On the contrary, expression of both NF-kappa B and I kappa B was mainly concentrated in the cytoplasm of endothelial and inflammatory cells. CONCLUSION: We detected activation of NF-kappa B in the endothelium and perivascular infiltrating inflammatory cells within the cerebral AVM nidus, suggesting a role in the pathophysiology of cerebral AVM.