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

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-kappaB) activity and tumor necrosis factor-alpha (TNF-alpha) 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-alpha levels and NF-kappaB 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-alpha expression and NF-kappaB 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 < or =20% may induce cerebral damage and should be avoided. NF-kappaB activation and TNF-alpha expression may play a functional role under the ischemic condition. A better understanding of the role of NF-kappaB and TNF-alpha in the brain may lead to a novel approach for preventing and treating various neurological disorders.