کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4352468 1298116 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Proteasomal inhibition in intracerebral hemorrhage: Neuroprotective and anti-inflammatory effects of bortezomib
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Proteasomal inhibition in intracerebral hemorrhage: Neuroprotective and anti-inflammatory effects of bortezomib
چکیده انگلیسی

Inflammation is an important pathophysiologic mechanism of injury induced by intracerebral hemorrhage (ICH). The ubiquitin-proteasome system (UPS) regulates the inflammatory responses via the up-regulation of several pro-inflammatory molecules. In this study, we determined that a potent proteasome inhibitor, bortezomib, exerted therapeutic effects in experimental model of ICH. Either bortezomib (0.05, 0.2, 0.5, 1 mg/kg) or vehicle was intravenously administered 2 h after ICH induction. The high doses of bortezomib caused high mortality rates. Bortezomib at 0.2 mg/kg reduced the early hematoma growth and alleviated hematoma volume and brain edema at 3 days after ICH, compared with the ICH-vehicle group. The numbers of myeloperoxidase+ neutrophils, Ox42+ microglia, and TUNEL+ cells in the perihematomal regions were decreased by bortezomib. Bortezomib induced significant decrements of mRNA expression of TNF-α and IL-6. The production of iNOS and COX2 was also reduced significantly by bortezomib. We concluded that the early treatment with bortezomib induced a reduction in the early hematoma growth and mitigated the development of brain edema, coupled with a marked inhibitory effect on inflammation in ICH.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Research - Volume 58, Issue 1, May 2007, Pages 12–18
نویسندگان
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