title: Minocycline Attenuates Iron-Induced Brain Injury.
abstract: Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Wenqaun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA. yahua@umich.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000418:Albumins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002712:Chlorides / Q000633:toxicity*; D005293:Ferritins / Q000187:drug effects / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D058085:Iron Compounds / Q000633:toxicity*; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000418:Albumins; D000900:Anti-Bacterial Agents; D002712:Chlorides; D058085:Iron Compounds; D005293:Ferritins; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D008911:Minocycline
keywords: Blood-brain barrier; Brain swelling; Intracerebral hemorrhage; Iron; Minocycline