Liu Hao, Rose Marie E, Culver Sherman, Ma Xiecheng, Dixon C Edward, Graham Steven H
Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, PA, USA.
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.
Biochem Biophys Res Commun. 2016 Apr 15;472(4):648-55. doi: 10.1016/j.bbrc.2016.03.003. Epub 2016 Mar 3.
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.
罗格列酮是一种强效的过氧化物酶体增殖物激活受体（PPAR）-γ激动剂，已被证明在中风和脊髓损伤中具有神经保护作用，但其在创伤性脑损伤（TBI）中的作用仍存在争议。本研究采用大鼠控制性皮质撞击模型，旨在确定罗格列酮治疗（损伤后5分钟、6小时和24小时给予6mg/kg）对TBI后21天炎症和组织学结果的影响。此外，还在更早的时间点（分别为损伤后24小时、1-5天、14-20天）确定了罗格列酮对炎性细胞因子转录、前庭运动行为和空间记忆功能的影响。与 Vehicle 治疗组相比，罗格列酮治疗可抑制TBI后24小时TNFα的产生，减轻小胶质细胞/巨噬细胞的激活，并增加CA3神经元的存活，但对TBI后21天的损伤体积没有影响。罗格列酮治疗的动物在平衡木测试中的表现有所改善，但在Morris水迷宫测定的空间记忆功能方面没有差异。总之，本研究表明，TBI后24小时内给予罗格列酮治疗对大鼠创伤性损伤具有有限的抗炎和神经保护作用。可能需要使用替代剂量模式和更敏感的行为测试进行进一步研究。
