S-Space College of Medicine/School of Medicine (의과대학/대학원) Neuroscience (뇌신경과학전공) Journal Papers (저널논문_뇌신경과학전공)
Proteasomal inhibition in intracerebral hemorrhage: neuroprotective and anti-inflammatory effects of bortezomib
- Sinn, D. I.; Lee, S. T.; Chu, K.; Jung, K. H.; Kim, E. H.; Kim, J. M.; Park, D. K.; Song, E. C.; Kim, B. S.; Yoon, S. S.; Kim, M.; Roh, J. K.
- Issue Date
- Neurosci Res. 2007 May;58(1):12-8. Epub 2007 Jan 19.
- Animals; Anti-Inflammatory Agents/pharmacology; Biological Markers/analysis/metabolism; Boronic Acids/*pharmacology; Brain Edema/drug therapy/etiology/physiopathology; Cerebral Cortex/blood supply/*drug effects/physiopathology; Cerebral Hemorrhage/complications/*drug therapy/physiopathology; Cytokines/antagonists & inhibitors/genetics; Disease Models, Animal; Dose-Response Relationship, Drug; Encephalitis/*drug therapy/etiology/physiopathology; Gliosis/drug therapy/etiology/physiopathology; Inflammation Mediators/antagonists & inhibitors/metabolism; Male; Microglia/drug effects/immunology/metabolism; Neuroprotective Agents/pharmacology; Neutrophils/drug effects/immunology/metabolism; Protease Inhibitors/*pharmacology; Proteasome Endopeptidase Complex/*drug effects/metabolism; Pyrazines/*pharmacology; RNA, Messenger/drug effects/metabolism; Rats; Rats, Sprague-Dawley; Treatment Outcome
- 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, 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.
- 0168-0102 (Print)
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