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Updated: May 12, 2026
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
Geldanamycin treatment during cerebral ischemia/reperfusion attenuates p44/42 mitogen-activated protein kinase
Murat Karabiyikoglu1, Ya Hua, Richard F Keep
1Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Background:
Heat-shock protein 90 (Hsp90) inhibitor geldanamycin was found to be neuroprotective in various experimental models of brain disease. The effect was attributed to the induction of heat-shock proteins and/or disruption of cellular signaling.
Methods:
In Sprague-Dawley rats, the middle cerebral artery was occluded for 90 min using the intraluminal suture method. Geldanamycin (300 mg/kg) or vehicle was injected intraperitoneally 15 min before onset of ischemia or reperfusion. Animals were sacrificed at 2, 4 or 24 h after ischemia onset and brain samples were processed for infarct volume measurement, Western blot analysis or immunofluorescent staining of Hsp90, Raf-1, p38, and p44/42 mitogen-activated protein kinases (MAPKs).
Results:
Geldanamycin treatment during ischemia or reperfusion reduced infarct volume by 79 and 61 % respectively. Geldanamycin decreased Raf-1 and activated p44/42 MAPK proteins, but did not alter levels of activated p38 MAPK during early reperfusion. Hsp90 was co-localized with Raf-1 and activated p44/42 MAPK in the cytoplasm of ischemic neurons.
Conclusion:
Geldanamycin-induced protection against transient focal cerebral ischemia may in part be based upon depletion of Raf-1 and blockade of p44/42 MAPK activation.
