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Ren C, Li N, Wang B, et al. Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia. Aging Dis. 2015;6(6):406-17doi: 10.14336/AD.2015.0812.
Ren, C., Li, N., Wang, B., Yang, Y., Gao, J., Li, S., Ding, Y., Jin, K., & Ji, X. (2015). Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia. Aging and disease, 6(6), 406-17. https://doi.org/10.14336/AD.2015.0812
Ren, Changhong, et al. "Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia." Aging and disease vol. 6,6 (2015): 406-17. doi: https://doi.org/10.14336/AD.2015.0812
Ren C, Li N, Wang B, Yang Y, Gao J, Li S, Ding Y, Jin K, Ji X. Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia. Aging Dis. 2015 Nov 17;6(6):406-17. doi: 10.14336/AD.2015.0812. eCollection 2015 Nov. PMID: 26618042; PMCID: PMC4657812.
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Aging Dis. 2015 Nov 17;6(6):406-17. doi: 10.14336/AD.2015.0812. eCollection 2015 Nov.

Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia.

Aging and disease

Changhong Ren, Ning Li, Brian Wang, Yong Yang, Jinhuan Gao, Sijie Li, Yuchuan Ding, Kunlin Jin, Xunming Ji

Affiliations

  1. 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA ; 6 Center of Stroke, Beijing Institute for Brain Disorder, Beijing, China ; 7 Beijing Key Laboratory of Hypoxia Translational Medicine. Beijing, China.
  2. 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 6 Center of Stroke, Beijing Institute for Brain Disorder, Beijing, China.
  3. 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
  4. 3 Department of Herbal Medicine, School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, China.
  5. 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
  6. 4 Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
  7. 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
  8. 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 5 Cerebrovascular Diseases Research Institute, Xuanwu Hospital, Capital Medical University, Beijing, China.

PMID: 26618042 PMCID: PMC4657812 DOI: 10.14336/AD.2015.0812

Abstract

Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke.

Keywords: blood-brain barrier; ischemic stroke; matrix metalloproteinases; remote ischemic perconditioning; tight junction

References

  1. PLoS One. 2012;7(2):e30892 - PubMed
  2. J Surg Res. 2012 Dec;178(2):797-806 - PubMed
  3. Stroke. 2001 Dec 1;32(12):2762-7 - PubMed
  4. Stroke. 1996 Sep;27(9):1616-22; discussion 1623 - PubMed
  5. Vis Neurosci. 2014 May;31(3):245-52 - PubMed
  6. CNS Neurosci Ther. 2012 Oct;18(10 ):855-63 - PubMed
  7. Mol Neurobiol. 2014 Feb;49(1):563-73 - PubMed
  8. Neurol Res. 2011 Jun;33(5):514-9 - PubMed
  9. Nat Cell Biol. 2008 Aug;10(8):883-5 - PubMed
  10. Neurosurgery. 2014 Nov;75(5):590-8; discussion 598 - PubMed
  11. Mol Pharmacol. 2003 Dec;64(6):1530-40 - PubMed
  12. Stroke. 2004 Apr;35(4):998-1004 - PubMed
  13. Neurol Res. 2012 Mar;34(2):143-8 - PubMed
  14. J Neurosci. 2001 Oct 1;21(19):7724-32 - PubMed
  15. Stroke. 2007 Sep;38(9):2563-8 - PubMed
  16. BMC Neurosci. 2009 Jun 04;10:56 - PubMed
  17. Restor Neurol Neurosci. 2012;30(6):491-5 - PubMed
  18. Stroke. 2011 Nov;42(11):3323-8 - PubMed
  19. Stroke. 2014 Jan;45(1):159-67 - PubMed
  20. Pharmacol Rev. 2005 Jun;57(2):173-85 - PubMed
  21. Brain Struct Funct. 2015 Jan;220(1):13-26 - PubMed
  22. J Neurochem. 2009 Feb;108(3):811-20 - PubMed
  23. Stroke. 2012 Oct;43(10):2794-9 - PubMed
  24. Acta Neuropathol. 2009 Aug;118(2):197-217 - PubMed
  25. Cell Mol Neurobiol. 2006 Mar;26(2):109-18 - PubMed
  26. J Cell Biol. 1996 Aug;134(4):1031-49 - PubMed
  27. Stroke. 2011 Feb;42(2):439-44 - PubMed
  28. Aging Dis. 2015 Aug 01;6(4):245-53 - PubMed
  29. Transl Stroke Res. 2014 Aug;5(4):484-90 - PubMed
  30. Neuroreport. 2001 Sep 17;12(13):3003-7 - PubMed
  31. J Neurosci. 2012 Feb 29;32(9):3044-57 - PubMed
  32. Neuroscience. 2012 May 3;209:155-60 - PubMed
  33. Biochem Biophys Res Commun. 2006 Jan 27;339(4):1197-203 - PubMed
  34. Aging Dis. 2014 Mar 08;5(6):366-72 - PubMed
  35. Brain Res. 1996 Nov 11;739(1-2):88-96 - PubMed
  36. J Cereb Blood Flow Metab. 2010 Apr;30(4):837-48 - PubMed
  37. Cardiol Res Pract. 2012;2012:620681 - PubMed
  38. Neurobiol Dis. 2008 Nov;32(2):200-19 - PubMed
  39. J Cereb Blood Flow Metab. 2007 Apr;27(4):697-709 - PubMed
  40. Histochem Cell Biol. 2008 Jul;130(1):55-70 - PubMed
  41. Vascul Pharmacol. 2002 Jun;38(6):323-37 - PubMed
  42. Free Radic Biol Med. 2005 Jul 1;39(1):51-70 - PubMed
  43. Brain Res. 2009 Jul 14;1280:158-65 - PubMed

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