Ran Lv1, Wei Zhou, Manlin Duan, Yali Ge, Taidi Zhong. 1. 1Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. nuzwlvran@yahoo.com.cn
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-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.
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.
Authors: F C Barone; B Arvin; R F White; A Miller; C L Webb; R N Willette; P G Lysko; G Z Feuerstein Journal: Stroke Date: 1997-06 Impact factor: 7.914