• Dong-In Sinn, Soon-Tae Lee, Kon Chu, Keun-Hwa Jung, Eun-Hee Kim, Jeong-Min Kim, Dong-Kyu Park, Eun-Cheol Song, Byung-Su Kim, Sung-Soo Yoon, Manho Kim, and Jae-Kyu Roh.
• Stroke & Neural Stem Cell Laboratory in Clinical Research Institute, Department of Neurology, Seoul National University Hospital, Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.
• Neurosci. Res. 2007 May 1;58(1):12-8.

AbstractInflammation 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, 1mg/kg) or vehicle was intravenously administered 2h 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-alpha 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.

64 keywords...

hide…