期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2004
卷号:101
期号:34
页码:12730-12735
DOI:10.1073/pnas.0404880101
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a powerful arteriogenic factor in the hypoperfused rat brain. To test the pathophysiological relevance of this response, the influence of GM-CSF on brain energy state was investigated in a model of hemodynamic stroke. Sprague-Dawley rats were submitted to three-vessel (bilateral vertebral and unilateral common carotid artery) occlusion (3-VO) to induce unilaterally accentuated brain hypoperfusion. One week later, hemodynamic stroke was induced by additional lowering of arterial blood pressure. Experiments were terminated by in situ freezing of the brain. ATP was measured in cryostat sections by using a bioluminescence method. The use of 3-VO, in combination with 15 min of hypotension of 50, 40, or 30 mmHg, did not produce disturbances of energy metabolism, however, focal areas of ATP depletion were unilaterally detected after 3-VO, in combination with 15 min of hypotension of 20 mmHg. Treating such animals with GM-CSF (40 {micro}g{middle dot}kg-1{middle dot}d-1) during the 1-week interval between 3-VO and induced hypotension significantly reduced the hemispheric volume of energy depletion from 48.8 {+/-} 44.2% (untreated group, n = 10) to 15.8 {+/-} 17.4% (treated group, n = 8, P = 0.033). GM-CSF-induced arteriogenesis is another approach to protect the brain against ischemic injury.
关键词:collateral circulation ; cerebrovascular circulation ; prevention of stroke ; brain vessels ; rat