Acta Neuropathologica

, Volume 114, Issue 5, pp 459–469 | Cite as

Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood–brain barrier breakdown

  • Sukriti NagEmail author
  • Roopa Venugopalan
  • Duncan J. Stewart
Original Paper


The significance of caveolin-1, a major constituent of caveolae, and the tight junction proteins occludin and claudin-5 in early blood–brain barrier (BBB) breakdown was assessed by sequential demonstration of the expression of these proteins over a period of 12 h to 6 days post-lesion in the rat cortical cold injury model. Pial and intracerebral vessels of control rats showed punctuate endothelial immunoreactivity for caveolin-1 and caveolin-2, while claudin-5 and occludin were localized as longitudinal strands in endothelium. During the early phase of BBB breakdown following injury at 12 h and on day 2, western blot analyses detected a significant increase in caveolin-1 expression at the lesion site while immunohistochemistry showed that the caveolin-1 increase was localized to the endothelium of lesion vessels. Decreased expression of occludin occurred at the lesion site only on days 2 and 4 post-lesion while claudin-5 expression was decreased only on day 2. Dual labeling for fibronectin, a marker of BBB breakdown, and caveolin-1 or the tight junction proteins demonstrated that only lesion vessels with BBB breakdown showed a marked increase of caveolin-1, loss of occludin and reduced localization of claudin-5. The issue whether these alterations precede or follow BBB breakdown is uncertain; however, increased expression of caveolin-1 preceded the decreased expression of occludin and claudin-5. Thus caveolae and caveolin-1 have an important role in early BBB breakdown and could be potential therapeutic targets in the control of early brain edema.


Blood–brain barrier Caveolae Caveolin-1 Claudin-5 Occludin Cold-injury Tight junctions 



The authors thank Dr. James Eubanks for helpful suggestions throughout this work and for reviewing this manuscript. Supported by Heart and Stroke Foundation of Ontario, Grant #5347


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sukriti Nag
    • 1
    • 3
    Email author
  • Roopa Venugopalan
    • 1
  • Duncan J. Stewart
    • 2
  1. 1.Toronto Western Research Institute, University Health NetworkUniversity of TorontoTorontoCanada
  2. 2.Terrance Donnelly Heart Center, St Michael’s HospitalUniversity of TorontoTorontoCanada
  3. 3.Department of Laboratory Medicine and PathobiologyBanting InstituteTorontoCanada

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