Changes of hypoxia-inducible factor-1 signaling and the effect of cilostazol in chronic cerebral ischemia*

I have no idea what this is useful for but I'm quite positive your doctor won't either. So call up your stroke association and ask for a detailed analysis and the translational work they are doing to get it into a stroke protocol. At least that's what a great stroke association would do.
http://www.sjzsyj.org:8080/Jweb_sjzs/CN/article/downloadArticleFile.do?attachType=PDF&id=651
Research Highlights
(1) Hypoxia-inducible factor-1 under hypoxia is a hot topic in the field of neural regeneration re-search. Under hypoxia and ischemia/reperfusion, heme oxygenase-1 is upregulated by hypox-ia-inducible factor-1. The available research mainly focuses on the role of hypoxia-inducible factor-1 and heme oxygenase-1 following acute cerebral ischemia and hypoxia, while very few studies have examined changes in the hypoxia-inducible factor-1/heme oxygenase-1 signaling pathway.
(2) This is the first report showing that the hypoxia-inducible factor-1/heme oxygenase-1 signaling pathway is activated and sustained following chronic cerebral ischemia.
(3) Hypoxia-inducible factor-1 and heme oxygenase-1 expression was downregulated by cilostazol in rats subjected to chronic cerebral ischemia. Our findings are the first to show that cilostazol pro-tects against apoptosis in the fontal cortex of chronic cerebral ischemic rats. Cilostazol can provide protection against vascular cognitive impairment through its anti-apoptotic effect.
Abstract
Hypoxia-inducible factor-1 and its specific target gene heme oxygenase-1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hypox-ia-inducible factor-1/heme oxygenase-1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol (30 mg/kg) for 9 weeks. Morris water maze results showed that cognitive impairment gradually worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative PCR and western blot analysis showed that hypoxia-inducible factor-1α and heme oxygenase-1 expression levels in-creased after chronic cerebral ischemia, with hypoxia-inducible factor-1α expression peaking at 3 weeks and heme oxygenase-1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxia-inducible factor-1α may upregulate heme oxygenase-1 expression fol-lowing chronic cerebral ischemia and that the hypoxia-inducible factor-1/heme oxygenase-1 sig-naling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment alleviated the cognitive impairment in rats with chronic cerebral is-chemia, decreased hypoxia-inducible factor-1α and heme oxygenase-1 expression levels, and re-duced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an anti-apoptotic mecha-nism.