Ultrastructural changes, nuclear factor-κB activation, and tumor necrosis factor-α expression in brain after acute normovolemic hemodilution and controlled hypotension in rats

Abstract

Aim: To examine brain damage following different degrees of acute normovolemic hemodilution combined with controlled hypotension (ANH-CH) by neuronal morphological analysis and investigate the expression of nuclear factor-kappa B (NF-κB) activity and tumor necrosis factor-alpha (TNF-α) in the rat. Methods: Forty rats were randomly assigned to receive a sham operation or ANH-CH (with hematocrit 30%, 25%, 20%, and 15%). ANH was performed after baseline physiological parameters had been monitored for 20 minutes. CH was induced 30 minutes later using sodium nitroprusside and mean arterial pressure was maintained at 50-60 mm Hg for 1 hour. Rats were euthanatized 3 and a half hours after operation. TNF-α levels and NF-κB activities in cerebral temporal cortex were measured. Ultrastructural alterations in the CA1 region of the rat hippocampi were observed. Changes in mitochondria were evaluated semiquantitatively. Results: Marked ultrastructural alterations, such as mitochondrial denaturalization and nucleus distortion, were observed in the CA1 region of the hippocampus in the ANH-CH hematocrit 20% group and ANH-CH hematocrit 15% group. TNF-α expression and NF-κB activity in the cerebral temporal cortex significantly increased in all ANH-CH groups and peaked in the ANH-CH hematocrit 25% group. Conclusion: Severe ANH-CH with hematocrit ≤20% may induce cerebral damage and should be avoided. NF-κB activation and TNF-α expression may play a functional role under the ischemic condition. A better understanding of the role of NF-κB and TNF-α in the brain may lead to a novel approach for preventing and treating various neurological disorders.