Long-term assessment of NFkappaB expression in the brain and neurologic outcome following deep hypothermic circulatory arrest in rats.
OBJECTIVE
Inflammatory response is discussed as a contributor to neurologic deficits following cardiac surgery using deep hypothermic circulatory arrest (DHCA). Nuclear Factor Kappa B (NFkappaB) 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 NFkappaB 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 degrees Celsius) and randomly assigned to 1, 3, 7, 14 and 28 days of postoperative survival. Untreated animals served as control (n=6). Cerebral NFkappaB expression was analyzed immunohistochemically, cyclooxygenase-2 (COX-2) and inhibitor of kappa B-alpha (IkappaBalpha) 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 NFkappaB 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 IkappaBalpha 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 NFkappaB-expression in the ischemia-sensitive hippocampus, accompanied by neurologic dysfunction and histologic damage following 45min of DHCA in rats.
Kellermann
Kristine
K
Klinik für Anesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaningerstrasse 22, 81675 München, Germany. k.kellermann@lrz.tum.de
Gordan
M Lucia
ML
Nollert
Georg
G
Blobner
Manfred
M
Kochs
Eberhard F
EF
Jungwirth
Bettina
B
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000628:therapy; D002315:Cardiopulmonary Bypass; D050792:Circulatory Arrest, Deep Hypothermia Induced; D005786:Gene Expression Regulation; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome
D016328:NF-kappa B