Expression of endothelial phosphorylated caveolin‐1 is increased in brain injury
pmid: 19508446
Expression of endothelial phosphorylated caveolin‐1 is increased in brain injury
Aims: Increased endothelial caveolae leading to transcytosis of plasma proteins is associated with blood–brain barrier (BBB) breakdown and cerebral oedema in brain injury. Increased expression of caveolin‐1α (Cav‐1), an integral caveolar membrane protein, was reported in endothelium of arterioles and veins with BBB breakdown to fibronectin post injury. In this study the phosphorylation state of Cav‐1 and its association with BBB breakdown was determined in the rat cortical cold injury model over a period of days 0.5–6 post lesion. Methods: Expression of phosphorylated Cav‐1 was determined by immunoblotting and dual labelling immunofluorescence for phosphorylated caveolin‐1 and fibronectin, a marker of BBB breakdown. A phospho‐specific monoclonal antibody that selectively recognizes only tyrosine 14‐phosphorylated Cav‐1 (PY14Cav‐1) was used. Results: Immunoblots showed constitutive expression of PY14Cav‐1 in cortex of control rats and a significant increase in PY14Cav‐1 expression at the lesion site up to day 4 post lesion. PY14Cav‐1 immunostaining was observed in the endothelium of lesion vessels at days 0.5–4 post lesion, in neutrophils at days 0.5 and 2 and in macrophages at day 6 post lesion. Dual labelling showed that 100% of vessels with BBB breakdown to fibronectin showed endothelial PY14Cav‐1 on day 0.5, the percentage decreasing to 62% on day 4. On day 6, none of the vessels showed endothelial phosphorylated Cav‐1. Conclusions: The presence of phosphorylated Cav‐1 in endothelium of vessels showing BBB breakdown suggests that phosphorylated Cav‐1 signalling may be one of the factors associated with early BBB breakdown and brain oedema in brain injury.
- University of Ottawa Canada
- University of Toronto Canada
Cerebral Cortex, Male, Microscopy, Confocal, Time Factors, Neutrophils, Macrophages, Blotting, Western, Caveolin 1, Fluorescent Antibody Technique, Fibronectins, Rats, Blood-Brain Barrier, Brain Injuries, Animals, Endothelium, Vascular, Phosphorylation, Rats, Wistar
Cerebral Cortex, Male, Microscopy, Confocal, Time Factors, Neutrophils, Macrophages, Blotting, Western, Caveolin 1, Fluorescent Antibody Technique, Fibronectins, Rats, Blood-Brain Barrier, Brain Injuries, Animals, Endothelium, Vascular, Phosphorylation, Rats, Wistar
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