title: Holo-transferrin and thrombin can interact to cause brain damage.
abstract: OBJECTIVE
  Previous studies have suggested that delayed release of hemoglobin degradation products, particularly iron, is involved in intracerebral hemorrhage (ICH)-induced brain injury. However, a recent study found evidence of iron-induced brain injury soon after ICH. This study, therefore, examined whether another iron-containing component of blood, holo-transferrin (holo-Tf), might also induce brain injury either alone or in combination with thrombin, another factor involved in early ICH-induced brain injury.
  
  
  METHODS
  Male Sprague-Dawley rats received an intracerebral infusion of holo-Tf, apo (noniron-loaded)-Tf, thrombin, or a combination of Tf with thrombin into the right basal ganglia. The rats were euthanized 24 hours later for measurement of brain edema and assessment of DNA damage (single- and double-strand breaks and 8-hydroxyl-2'-deoxyguanosine immunohistochemistry). Iron distribution was examined histochemically.
  
  
  RESULTS
  Holo-Tf, apo-Tf, and the dose of thrombin used (1 U) all failed to induce brain edema when administered alone. However, the combination of holo-Tf with thrombin (but not apo-Tf with thrombin) caused brain edema, DNA damage, and intracellular iron accumulation in the ipsilateral basal ganglia.
  
  
  CONCLUSIONS
  These results suggest that in addition to hemoglobin-bound iron, Tf-bound iron may contribute to ICH-induced brain injury and that thrombin may contribute to the latter by facilitating cellular iron uptake.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.forename: Jung-Weon
authors.initials: JW
authors.lastname: Park
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.forename: Julian T
authors.initials: JT
authors.lastname: Hoff
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002543:Cerebral Hemorrhage; D004249:DNA Damage; D053938:DNA Fragmentation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007501:Iron / Q000493:pharmacokinetics; D000072200:Ku Autoantigen; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry*; D014867:Water / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D006454:Hemoglobins; D014168:Transferrin; C110714:holotransferrin; D014867:Water; D007501:Iron; D013917:Thrombin; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen