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Proteasomal inhibition in intracerebral hemorrhage: neuroprotective and anti-inflammatory effects of bortezomib

Cited 34 time in Web of Science Cited 36 time in Scopus
Authors
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
2007-03-03
Publisher
Elsevier
Citation
Neurosci Res. 2007 May;58(1):12-8. Epub 2007 Jan 19.
Keywords
AnimalsAnti-Inflammatory Agents/pharmacologyBiological Markers/analysis/metabolismBoronic Acids/*pharmacologyBrain Edema/drug therapy/etiology/physiopathologyCerebral Cortex/blood supply/*drug effects/physiopathologyCerebral Hemorrhage/complications/*drug therapy/physiopathologyCytokines/antagonists & inhibitors/geneticsDisease Models, AnimalDose-Response Relationship, DrugEncephalitis/*drug therapy/etiology/physiopathologyGliosis/drug therapy/etiology/physiopathologyInflammation Mediators/antagonists & inhibitors/metabolismMaleMicroglia/drug effects/immunology/metabolismNeuroprotective Agents/pharmacologyNeutrophils/drug effects/immunology/metabolismProtease Inhibitors/*pharmacologyProteasome Endopeptidase Complex/*drug effects/metabolismPyrazines/*pharmacologyRNA, Messenger/drug effects/metabolismRatsRats, Sprague-DawleyTreatment Outcome
Abstract
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.
ISSN
0168-0102 (Print)
Language
English
URI
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0H-4MVN0VG-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d8af336df0b6995eabcb98d1713c882d

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17328981

https://hdl.handle.net/10371/22326
DOI
https://doi.org/10.1016/j.neures.2007.01.006
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College of Medicine/School of Medicine (의과대학/대학원)Neuroscience (뇌신경과학전공)Journal Papers (저널논문_뇌신경과학전공)
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