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Neurol Res. 2008 Sep;30(7):740-5. doi: 10.1179/174313208X289615. Epub 2008 Jun 3.

Geldanamycin protects rat brain through overexpression of HSP70 and reducing brain edema after cerebral focal ischemia.

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  • 1Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea.

Abstract

OBJECTIVE:

Geldanamycin (GA), a benzoquinone ansamycin, binds HSP90, releases heat shock factor 1 and induces heat shock proteins (HSPs). HSP70, a major molecular chaperone, protects the brain against ischemic injury through inhibition of apoptotic pathways in vivo and reduced matrix metalloproteinase 9 (MMP-9) after ischemia in vitro. We hypothesized that GA would protect brain from focal ischemia via induction of HSP70 and MMP suppression in vivo.

METHODS:

GA or vehicle was injected into the lateral cerebral ventricles of adult male Sprague-Dawley rats using the stereotatic frame 24 hours before ischemia. Rats were subjected to 2 hour middle cerebral artery occlusions using the suture technique followed by 22 hour reperfusions. One day after ischemia, we evaluated infarction volume, brain swelling, behavioral scores and immunohistochemistry.

RESULTS:

Western blots showed that GA at 2 mug/kg induced HSP70 by 24 hours following administration. GA decreased infarct volumes and brain edema, and improved behavioral outcomes (p<0.05). Immunohistochemistry showed that GA induced HSP70 and decreased MMP-9.

DISCUSSION:

GA protects brain from focal ischemia and reduces edema. This may be due, at least in part, to GA overexpression of HSP70.

PMID:
18534054
[PubMed - indexed for MEDLINE]
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