机构：[a]Department of Neurosurgery, The University of Texas Health Science Center at San Antonio, Mail Code 7843, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA[b]Central Laboratories, Xuanwu Hospital, Capital Medical University, 100053 China首都医科大学宣武医院
Exercise reduces ischemia and reperfusion (I/R) injury in the rat stroke model. We investigated whether preischemic exercise ameliorates blood-brain barrier (BBB) dysfunction in stroke by reducing matrix metalloproteinase (MMP)-9 expression and strengthening basal lamina. Adult male Sprague-Dawley rats were subjected to a 30 min exercise program on a treadmill 5 days a week for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament in the exercised and non-exercised groups. Brain infarction was measured and neurological deficits were scored. BBB dysfunction was determined by examining brain edema and Evans Blue extravasation. Expression of collagen IV, the major component of basal lamina essential for maintenance of the endothelial permeability barrier, was quantitatively detected by Western blot and immunocytochemistry. Ex vivo techniques were used to compare collagen IV-labeled vessels in response to ischemic insult. Temporal relationship of expression of MMP-9 and its endogenous inhibitor, the tissue inhibitors of metalloproteinase-1 (TIMP-1), was determined by real-time PCR for mRNA and Western blot for protein during reperfusion. Brain edema and Evans Blue leakage were both significantly (P<0.01) reduced after stroke in the exercised group, in association with reduced brain infarct volume and neurological deficits. Western blot analysis indicated that exercise enhanced collagen IV expression and reduced the collagen loss after stroke. Immunocytochemistry demonstrated that collagen IV-labeled vessels were significantly (P<0.01) increased in exercised rats. In the ex vivo study, after exercised brains were incubated with ischemic brain tissue, a significantly (P<0.01) higher level of collagen IV-labeled vessels was observed as compared with non-exercised brains following the same treatment. The ex vivo study also revealed a key role of MMP-9 in exercise-strengthened collagen IV expression against I/R injury. TIMP-1 protein levels were significantly (P<0.01) increased by exercise. Our results indicate that pre-ischemic exercise reduces brain injury by improving BBB function and enhancing basal lamina integrity in stroke. This study suggests that the neuroprotective effect of physical exercise is associated with an imbalance of MMP-9 and TIMP-1 expression. (C) 2008 Published by Elsevier Ltd on behalf of IBRO.
基金：
American Heart Association Grant in Aid and UTHSCSA Neurosurgery Research Stimulation Fund
第一作者机构：[a]Department of Neurosurgery, The University of Texas Health Science Center at San Antonio, Mail Code 7843, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA[b]Central Laboratories, Xuanwu Hospital, Capital Medical University, 100053 China
通讯作者：
通讯机构：[a]Department of Neurosurgery, The University of Texas Health Science Center at San Antonio, Mail Code 7843, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
推荐引用方式(GB/T 7714)：
M. GUO ,B. COX ,S. MAHALE ,et al.Pre-ischemic exercise reduces matrix metalloproteinase-9 expression and ameliorates blood-brain barrier dysfunction in stroke[J].NEUROSCIENCE.2008,151(2):340-351.doi:10.1016/j.neuroscience.2007.10.006.
APA：
M. GUO,,B. COX,,S. MAHALE,,W. DAVIS,,A. CARRANZA,...&Y. DING.(2008).Pre-ischemic exercise reduces matrix metalloproteinase-9 expression and ameliorates blood-brain barrier dysfunction in stroke.NEUROSCIENCE,151,(2)
MLA：
M. GUO,,et al."Pre-ischemic exercise reduces matrix metalloproteinase-9 expression and ameliorates blood-brain barrier dysfunction in stroke".NEUROSCIENCE 151..2(2008):340-351
医学