title: Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage.
abstract: OBJECTIVE
  Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo.
  
  
  METHODS
  This study was divided into 4 parts: (1) rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination; (2) rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured; (3) rats had an intracaudate injection of saline, iron, iron+minocycline, or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements; and (4) rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement.
  
  
  RESULTS
  After ICH, serum total iron and brain nonheme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage, and brain cell death, all of which were significantly reduced by coinjection with minocycline.
  
  
  CONCLUSIONS
  The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for patients with ICH because both iron accumulation and microglia activation contribute to brain damage after ICH.
authors: Department of Neurosurgery, R5018 Biomedical Science, Research Building, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
authors: Fan
authors: F
authors: Zhao
authors: Ya
authors: Y
authors: Hua
authors: Yangdong
authors: Y
authors: He
authors: Richard F
authors: RF
authors: Keep
authors: Guohua
authors: G
authors: Xi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007501:Iron; D008911:Minocycline