Estrogen receptors (ERs) play important roles in estrogen-mediated neuroprotection. However, their effects on blood-brain barrier (BBB) disruption with vasogenic edema after ischemic stroke have not been determined. We evaluated a role for ERβ in the brain without effects in the peripheral reproductive organs for the amelioration of vasogenic edema following ischemic stroke. Transient focal ischemic stroke was induced in ovariectomized female C57BL/6 mice (age 10-11. weeks) that were treated with the ERβ-selective agonist diarylpropionitrile (DPN). BBB breakdown as determined by the extravasation of endogenous immunoglobulin G (IgG), vasogenic edema, and the infarct volume was significantly reduced by DPN compared to vehicle. Protein expressions of endothelial tight junction proteins (occludin and claudin-5) and the water channel protein aquaporin 4 in the ischemic cortex were not changed by DPN. However, protein levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α), a transcription factor that increases VEGF expression, were significantly decreased in the ischemic cortex by DPN. These results suggest that ERβ contributes to the reduction of vasogenic edema caused by BBB breakdown via the inhibition of HIF-1α and VEGF following ischemic stroke.
|Number of pages||9|
|State||Published - 3 Apr 2013|
Bibliographical noteFunding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government ( KRF-2008-331-E00055 ) and by Mid-career Researcher program through the National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science and Technology (MEST) ( 2011-0015923 and 2012-0009854 ).
- Blood-brain barrier disruption
- Estrogen receptor β
- Hypoxia-inducible factor 1α
- Ischemic stroke
- Vascular endothelial growth factor
- Vasogenic edema