title: Temporal changes in free iron levels after brain ischemia Relevance to the timing of iron chelation therapy in stroke.
abstract: Whereas iron chelators have been proposed as therapeutic agents in stroke, changes in free iron levels have never been explored after focal brain ischemia. Therefore, free and total iron levels in cortical tissue and free iron levels in plasma were measured before and after (1, 4 and 24h) photothrombotic occlusion of cortical vessels in rats. Brain ferritin expression and localization were also investigated before and after (24, 72 and 192 h) occlusion. The results showed that free iron remained below detectable levels in plasma and that the lesion exhibited high levels of free and total iron. As compared to contralateral values, free iron levels in ischemic core and penumbra increased (+50%) at 1h and returned to control values at 4h post-occlusion. In contrast, the increase in total iron levels (+20-30%) was long-lasting, but confined to the ischemic core. A time-dependent increase in the expression of both chains of ferritin was detected in regions that previously exhibited free iron accumulation. Finally, ischemic damage was reduced by the liposoluble iron chelator 2,2'-dipyridyl (20 mg/kg, i.p.) when injected 15 min or 1 h post-occlusion, yet not later (4 h). In conclusion, our results show that focal brain ischemia results in an early and transient elevation in free iron levels in the ischemic tissue and suggest that free iron excess does not originate in blood. They also highlight the importance of starting iron chelation therapy as soon as possible after stroke.
authors.affiliation: U887 INSERM Motricité-Plasticité, Dijon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Millerot-Serrurot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bertrand
authors.forename: Claude
authors.initials: C
authors.lastname: Mossiat
authors.forename: Philippe
authors.initials: P
authors.lastname: Faure
authors.forename: Anne
authors.initials: A
authors.lastname: Prigent-Tessier
authors.forename: Philippe
authors.initials: P
authors.lastname: Garnier
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bejot
authors.forename: Maurice
authors.initials: M
authors.lastname: Giroud
authors.forename: Alain
authors.initials: A
authors.lastname: Beley
authors.forename: Christine
authors.initials: C
authors.lastname: Marie
mesh_terms: D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D002614:Chelating Agents / Q000494:pharmacology; D015913:Chelation Therapy / Q000592:standards*; D004195:Disease Models, Animal; D005293:Ferritins / Q000378:metabolism; D020767:Intracranial Thrombosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002614:Chelating Agents; D007502:Iron Chelating Agents; D015082:2,2'-Dipyridyl; D005293:Ferritins; D007501:Iron