Potential dual role of nuclear factor-kappa B in experimental subarachnoid hemorrhage-induced early brain injury in rabbits

Nuclear factor-kappa B (NF-kappa B) has multiple physiological and pathological functions. The role of NF-kappa B can be protective or destructive. We aim to investigate the biphasic activation of NF-kappa B in brain after subarachnoid hemorrhage (SAH). Eighty male New Zealand rabbits are assigned to control, SAH, vehicle, and pyrrolidine dithiocarbamate (PDTC) groups. PDTC (3 mg/kg, dissolved in saline) was injected into cisterna magna. Immunofluorescence and electrophoretic mobility shift assay experiments were performed to assess the activation of NF-kappa B. The levels of inflammatory and apoptosis mediators were detected by ELISA and real-time polymerase chain reaction. Nissl and immunofluorescent stain was performed to evaluate neuron injury. NF-kappa B activity in the brain cortex showed two peaks after SAH. Inflammatory mediators exhibited similar time course. PDTC could significantly inhibit the NF-kappa B activity and inflammatory mediators. Suppressing the early NF-kappa B activity significantly decreased neuron injury, while inhibiting the late one could statistically increase neuron injury. The biphasic NF-kappa B activation in the brain cortex after SAH played a decisive role on neuronal fate through the inflammatory signaling pathway. The early NF-kappa B activity contributed to neuron damage after SAH. Nevertheless, the late activated NF-kappa B may serve as a protector.