title: Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats.
abstract: Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1-5 d, 14-20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted.
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Rose
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurosurgery, University of Pittsburgh, PA 15216, USA; Department of Critical Care Medicine, University of Pittsburgh, PA 15216, USA.
authors.forename: Sherman
authors.initials: S
authors.lastname: Culver
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurosurgery, University of Pittsburgh, PA 15216, USA; Department of Critical Care Medicine, University of Pittsburgh, PA 15216, USA.
authors.forename: Xiecheng
authors.initials: X
authors.lastname: Ma
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurosurgery, University of Pittsburgh, PA 15216, USA; Department of Critical Care Medicine, University of Pittsburgh, PA 15216, USA.
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, PA, USA. Electronic address: Steven.Graham@va.gov.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Graham
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone
keywords: Behavioral; Cell survival; Inflammation; PPARγ; Rosiglitazone; Traumatic brain injury