SHERP

Pharmacological induction of heat shock protein exerts neuroprotective effects in experimental intracerebral hemorrhage

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Authors
Sinn, Dong-In; Chu, Kon; Lee, Soon-Tae; Song, Eun-Cheol; Jung, Keun-Hwa; Kim, Eun-Hee; Park, Dong-Kyu; Kang, Kyung-Mook; Kim, Manho; Roh, Jae-Kyu
Issue Date
2007
Publisher
Elsevier
Citation
Brain Res. 1135, 167-176
Keywords
Intracerebral hemorrhageGeranylgeranylacetoneHeat shock proteinCell deathInflammationNeuroprotectant
Abstract
Heat shock proteins (HSPs) are reported to reduce inflammation and apoptosis in a variety of brain insults. Geranylgeranylacetone (GGA), developed as an antiulcer in Japan, has been known to induce HSP70 and to exert cytoprotective effects. In this study, we investigated whether GGA, as a specific HSP inducer, exerts therapeutic effects in experimentally induced intracerebral hemorrhage (ICH). ICH was induced with male Sprague-Dawley rats via the collagenase infusion. GGA (800 mg/kg) was administered via oral tube according to various schedules of treatment. The treatment with GGA, beginning before the induction of ICH and continuing until day 3, showed the reduction of brain water content and the increased level of HSP70 protein, as compared to the treatment with vehicle, although GGA started after the induction of ICH or administered as a single dose before ICH failed to up-regulate HSP70 and to reduce brain edema. The rats treated with GGA exhibited better functional recovery than those treated with vehicle. In the pre- and post- treatment group, inflammatory cells and cell death in the perihematomal regions were found to have been decreased. The treatment of GGA inhibited the mRNA expression of MMP-9, uPA, IL-6 and MIP-1, with concomitant increment of eNOS and phosphorylated STAT3 and Akt after ICH. We demonstrated that GGA induced a reduction in the brain edema along with marked inhibitory effects on inflammation and cell death after ICH.
ISSN
0006-8993 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17208204

http://hdl.handle.net/10371/11084
DOI
https://doi.org/10.1016/j.brainres.2006.11.098
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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