Long-term assessment of NFκB expression in the brain and neurologic outcome following deep hypothermic circulatory arrest in rats

Objectives: Inflammatory response is discussed as a contributor to neurologic deficits following cardiac surgery using deep hypothermic circulatory arrest (DHCA). Nuclear Factor Kappa B (NFκB) presents a central transcription factor whose expression pattern and subsequent role very much depend on the type and manner of cerebral injury. This study was designed to assess the time course of cerebral NFκB expression in relation to neurologic performance over 28 days following 45min of DHCA in rats. Methods: With Institutional Review Board approval, 30 rats were subjected to cardiopulmonary bypass (CPB) with 45min of DHCA (rectal temperature 15-18°C) and randomly assigned to 1, 3, 7, 14 and 28 days of postoperative survival. Untreated animals served as control (n=6). Cerebral NFκB expression was analyzed immunohistochemically, cyclooxygenase-2 (COX-2) and inhibitor of kappa B-alpha (IκBα) using Western Blot and the number of eosinophilic neurons with hematoxylin and eosin (HE) staining. Neurologic outcome was assessed pre- and postoperatively. Results: Neuronal expression of NFκB in the hippocampus peaked at day one, remaining elevated in the motor cortex until day 28. Rats showed neurologic deficits on postoperative day one. Cerebral COX-2 was increased during the first postoperative week and IκBα peaked on day 14. Histologic damage in the motor cortex and hippocampus persisted until day 28. No systemic inflammation was detectable postoperatively. Conclusions: Postoperative day one presents with the highest NFκB-expression in the ischemia-sensitive hippocampus, accompanied by neurologic dysfunction and histologic damage following 45min of DHCA in rats.