title: Tuftsin fragment 1-3 is beneficial when delivered after the induction of intracerebral hemorrhage.
abstract: OBJECTIVE
  Microglial activation may contribute to the pathogenesis of the brain injury in intracerebral hemorrhage (ICH). We have reported that the tripeptide macrophage/microglial inhibitory factor (MIF), Thr-Lys-Pro, inhibits microglial activation and results in functional improvement when given before the onset of hemorrhage. In this study, we investigate the protection and efficacy of treatment when MIF is administered 2 hours after collagenase injection.
  
  
  METHODS
  ICH was induced by injecting bacterial collagenase into the caudate nucleus; 100 microL MIF (500 micromol/L) was delivered via a micro-osmotic pump. Infusion of MIF or saline (control) was initiated 2 hours after collagenase injection and continued for 24 or 72 hours. Microglial activation and macrophage infiltration were assessed by 5-d-4 and F4/80 immunofluorescence, respectively. Production of reactive oxygen species was visualized by in situ detection of ethidium. Degenerating neurons were assessed by Fluoro-Jade B staining. Neurological deficits, brain injury volumes, and brain edema were assessed at 24 and 72 hours after MIF/saline treatment.
  
  
  RESULTS
  MIF can inhibit microglial activation and macrophage infiltration, attenuate the numbers of ethidium-positive cells compared with the saline-treated control mice, reduce the injury volume, edema, and degenerating neurons, and improve the neurological functional outcome.
  
  
  CONCLUSIONS
  Activated microglia/macrophages are important contributors to brain injury after ICH. MIF could be a valuable neuroprotective agent for the treatment of ICH, if treatment is initiated soon after the onset of hemorrhage.
authors.affiliation: Department of Pharmacological Sciences, University Medical Center at Stony Brook, Stony Brook, NY 11794-8651, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000517:prevention & control*; D002421:Caudate Nucleus / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000150:complications; D017364:Collagenases / Q000009:adverse effects; D004487:Edema / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000627:therapeutic use*; D011596:Psychomotor Disorders / Q000209:etiology / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D014405:Tuftsin / Q000627:therapeutic use*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D017364:Collagenases; D014405:Tuftsin