کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5630535 1580613 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia
چکیده انگلیسی


- A2b receptor expression increases more than other adenosine receptors after transient focal cerebral ischemia.
- tPA administration inhibits A2b receptor expression in microvessels of the ischemic brain.
- A2b receptor agonist attenuates tPA-induced blood-brain barrier disruption and hemorrhagic transformation.
- A2b receptor agonist elevates TIMP-1 expression and inhibits tPA-enhanced matrix MMP-9 activity.
- A2b receptor agonist protects tight junctions and the blood-brain barrier.

Tissue plasminogen activator (tPA) is administered after ischemic stroke to dissolve intravascular clots, but its use can lead to hemorrhagic transformation (HT). Therapeutic strategies to reduce hemorrhagic complications of tPA might be of benefit for stroke patients. Adenosine A2b receptor (A2bR) plays pivotal roles in regulating vascular protection in peripheral organs. This study explored whether A2bR agonist BAY 60-6583 reduces hemorrhage risk after tPA usage. Using a rat transient middle cerebral artery occlusion model, we showed that mRNA and protein expression of A2bR increased to a greater extent after ischemia-reperfusion than did expression of the other three adenosine receptors (A1, A2a, and A3). tPA administration reduced A2bR expression in ischemic brain microvessels. Post-treatment with BAY 60-6583 (1 mg/kg) at the start of reperfusion reduced lesion volume in the absence or presence of tPA (10 mg/kg) and attenuated brain swelling, blood-brain barrier disruption, and tPA-exacerbated HT at 24 h. Additionally, BAY 60-6583 mitigated sensorimotor deficits in the presence of tPA. BAY 60-6583 inhibited tPA-enhanced matrix metalloprotease-9 activation, probably through elevation of tissue inhibitor of matrix metalloproteinases-1 expression, and thereby reduced degradation of tight junction proteins. These effects would likely protect cerebrovascular integrity. A2bR agonists as an adjuvant to tPA could be a promising strategy for decreasing the risk of HT during treatment for ischemic stroke.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 108, December 2017, Pages 173-182
نویسندگان
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