title: Therapeutic benefits of delayed lithium administration in the neonatal rat after cerebral hypoxia-ischemia.
abstract: OBJECTIVE
  We have previously shown that lithium treatment immediately after hypoxia-ischemia (HI) in neonatal rats affords both short- and long-term neuroprotection. The aim of this study was to evaluate possible therapeutic benefits when lithium treatment was delayed 5 days, a time point when most cell death is over.
  
  
  METHODS
  Eight-day-old male rats were subjected to unilateral HI and 2 mmol/kg lithium chloride was injected intraperitoneally 5 days after the insult. Additional lithium injections of 1 mmol/kg were administered at 24 h intervals for the next 14 days. Brain injury was evaluated 12 weeks after HI. Serum cytokine measurements and behavioral analysis were performed before sacrificing the animals.
  
  
  RESULTS
  Brain injury, as indicated by tissue loss, was reduced by 38.7%, from 276.5±27.4 mm3 in the vehicle-treated group to 169.3±25.9 mm3 in the lithium-treated group 12 weeks after HI (p<0.01). Motor hyperactivity and anxiety-like behavior after HI were normalized by lithium treatment. Lithium treatment increased neurogenesis in the dentate gyrus as indicated by doublecortin labeling. Serum cytokine levels, including IL-1α, IL-1β, and IL-6, were still elevated as late as 5 weeks after HI, but lithium treatment normalized these cytokine levels.
  
  
  CONCLUSIONS
  Delayed lithium treatment conferred long-term neuroprotection in neonatal rats after HI, and this opens a new avenue for future development of treatment strategies for neonatal brain injury that can be administered after the acute injury phase.
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden; Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Xie
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden; Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Perinatal Center, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden; Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden; Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden; Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden; Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D000089662:Doublecortin Protein; D020925:Hypoxia-Ischemia, Brain / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats
chemical_list: D016207:Cytokines; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D018021:Lithium Chloride