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Acta Neuropathologica

, 112:74 | Cite as

Exercise preconditioning upregulates cerebral integrins and enhances cerebrovascular integrity in ischemic rats

  • Y. H. Ding
  • J. Li
  • W. X. Yao
  • J. A. Rafols
  • J. C. Clark
  • Y. DingEmail author
Original Paper

Abstract

We hypothesized that exercise preconditioning strengthens brain microvascular integrity against ischemia/reperfusion injury through the tumor necrosis factor (TNF)-integrin signaling pathway. Adult male Sprague Dawley rats (n = 24) were studied in: (1) exercise (the animals run on a treadmill 30 min each day) for 3 weeks, (2) non-exercise. Six animals from each group (n = 12) were subjected to stroke, the remaining animals served as controls (n = 6 × 2). Brain infarction and edema were determined by Nissl staining. Cerebral integrin expression was detected by immunochemistry and stereological methods. In addition, we used flow cytometry to address the causal role of TNF-α in inducing the expression of integrins in the human umbilical vein endothelial cells under TNF-α or vascular endothelial growth factor (VEGF) pretreatment. Exercise reduces brain infarction and brain edema in stroke. Expressions of integrin subunit α1, α6, β1, and β4 were increased after exercise. Exercise preconditioning reversed stroke-reduced integrin expression. An in vitro study revealed a causal link between the gradual upregulation of TNF-α (rather than VEGF) and cellular expression of integrins. These results demonstrated an increase in cerebral expression of integrins and a decrease in brain injury from stroke after exercise preconditioning. The study suggests that upregulation of integrins during exercise enhances neurovascular integrity after stroke. The changes in integrins might be altered by TNF-α.

Keywords

Stroke Blood–brain barrier Infarct Brain edema Cell culture Tumor necrosis factor-α Treadmill 

Notes

Acknowledgments

We are grateful to Yandong Zhou, MS and Lisa D. NeSmith, MA for their help in the preparation of this manuscript. This work was supported partially by American Heart Association Midwest Affiliate Grant in aid to Yuchuan Ding.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Y. H. Ding
    • 1
  • J. Li
    • 1
  • W. X. Yao
    • 2
  • J. A. Rafols
    • 3
  • J. C. Clark
    • 1
    • 4
  • Y. Ding
    • 1
    • 5
    Email author
  1. 1.Department of Neurological SurgeryWayne State University School of MedicineDetroitUSA
  2. 2.Department of Health and Kinesiology, College of Education and Human DevelopmentThe University of TexasSan AntonioUSA
  3. 3.Department of Anatomy and Cell BiologyWayne State University School of MedicineDetroitUSA
  4. 4.University of Michigan Medical SchoolAnn ArborUSA
  5. 5.Department of NeurosurgeryThe University of Texas Health Science CenterSan AntonioUSA

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