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  • Title: Tissue plasminogen activator prevents restoration of tight junction proteins through upregulation of angiopoietin-2.
    Author: Mishiro K, Ishiguro M, Suzuki Y, Tsuruma K, Shimazawa M, Hara H.
    Journal: Curr Neurovasc Res; 2013 Feb; 10(1):39-48. PubMed ID: 23151074.
    Abstract:
    We examined the temporal profiles of changes in the expressions of tight junction proteins (TJPs; namely, claudin-5, occludin, and ZO-1) after focal cerebral ischemia/reperfusion in mice. We also examined the effects of delayed treatment with tissue plasminogen activator (tPA) on the expressions of TJPs and angiopoietin (Ang) -1/2/Tie2. Mice subjected to a 6-h filamental middle cerebral artery (MCA) occlusion were treated with tPA (10 mg/kg, intravenously, just after the start of reperfusion) or vehicle. The expressions of TJPs were significantly decreased in the early phase of ischemia/reperfusion, and then gradually recovered. A delayed treatment with tPA decreased the expressions of TJPs when examined at 42 h after reperfusion. In contrast, delayed tPA treatment markedly increased Ang-2, but not Ang-1 expression, when examined at 30 h after reperfusion. Treatment with tPA at 300 μg/ml also significantly decreased Ang- 2, but not Tie2 expression, in an in vitro monolayer model generated using human brain microvascular endothelial cells subjected to serum-deprivation. These findings suggest that delayed tPA treatment prevents recovery of TJPs following focal cerebral ischemia/reperfusion, partially via upregulation of Ang-2.
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