期刊论文详细信息
BMC Neuroscience
Neuroglobin-overexpression reduces traumatic brain lesion size in mice
Xiaoying Wang4  Eng H Lo3  Josephine M Lok1  Michael J Whalen1  Kazuhide Hayakawa3  Changhong Xing3  Gang Zhao2  Zhanyang Yu3  Song Zhao3 
[1]Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
[2]Departments of Orthopedic and Neurosurgery, The First Bethune Hospital of Jilin University, Changchun, Jilin, China
[3]Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
[4]Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, 149 13th Street, Room 2401, Charlestown, MA, 02129, USA
关键词: Traumatic brain injury;    Oxidative stress;    Controlled cortical impact;    Neuroprotection;    Neuroglobin;   
Others  :  1170670
DOI  :  10.1186/1471-2202-13-67
 received in 2012-03-21, accepted in 2012-05-24,  发布年份 2012
PDF
【 摘 要 】

Background

Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. In this study we tested the neuroprotective effects of Ngb over-expression against traumatic brain injury (TBI) in mice.

Results

Both Ngb over-expression transgenic (Ngb-Tg) and wild-type (WT) control mice were subjected to TBI induced by a controlled cortical impact (CCI) device. TBI significantly increased Ngb expression in the brains of both WT and Ngb-Tg mice, but Ngb-Tg mice had significantly higher Ngb protein levels at the pre-injury baseline and post-TBI. Production of oxidative tissue damage biomarker 3NT in the brain was significantly reduced in Ngb-Tg mice compared to WT controls at 6 hours after TBI. The traumatic brain lesion volume was significantly reduced in Ngb Tg mice compared to WT mice at 3 weeks after TBI; however, there were no significant differences in the recovery of sensorimotor and spatial memory functional deficits between Ngb-Tg and WT control mice for up to 3 weeks after TBI.

Conclusion

Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress.

【 授权许可】

   
2012 Zhao et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150417023654347.pdf 788KB PDF download
Figure 4 . 51KB Image download
Figure 3 . 9KB Image download
Figure 2 . 19KB Image download
Figure 1 . 96KB Image download
【 图 表 】

Figure 1 .

Figure 2 .

Figure 3 .

Figure 4 .

【 参考文献 】
  • [1]Awenius C, Hankeln T, Burmester T: Neuroglobins from the zebrafish Danio rerio and the pufferfish Tetraodon nigroviridis. Biochem Biophys Res Commun 2001, 287(2):418-421.
  • [2]Burmester T, Weich B, Reinhardt S, Hankeln T: A vertebrate globin expressed in the brain. Nature 2000, 407(6803):520-523.
  • [3]Burmester T, Hankeln T: Neuroglobin: a respiratory protein of the nervous system. News Physiol Sci 2004, 19:110-113.
  • [4]Liu J, Yu Z, Guo S, Lee SR, Xing C, Zhang C, Gao Y, Nicholls DG, Lo EH, Wang X: Effects of neuroglobin overexpression on mitochondrial function and oxidative stress following hypoxia/reoxygenation in cultured neurons. J Neurosci Res 2009, 87(1):164-170.
  • [5]Wang X, Liu J, Zhu H, Tejima E, Tsuji K, Murata Y, Atochin DN, Huang PL, Zhang C, Lo EH: Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia. Stroke 2008, 39(6):1869-1874.
  • [6]Khan AA, Wang Y, Sun Y, Mao XO, Xie L, Miles E, Graboski J, Chen S, Ellerby LM, Jin K, et al.: Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia. Proc Natl Acad Sci USA 2006, 103(47):17944-17948.
  • [7]Khan AA, Mao XO, Banwait S, Jin K, Greenberg DA: Neuroglobin attenuates beta-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo. Proc Natl Acad Sci USA 2007, 104(48):19114-19119.
  • [8]Yu Z, Liu J, Guo S, Xing C, Fan X, Ning M, Yuan JC, Lo EH, Wang X: Neuroglobin-overexpression alters hypoxic response gene expression in primary neuron culture following oxygen glucose deprivation. Neuroscience 2009, 162(2):396-403.
  • [9]Jin K, Mao XO, Xie L, Khan AA, Greenberg DA: Neuroglobin protects against nitric oxide toxicity. Neurosci Lett 2008, 430(2):135-137.
  • [10]Khan AA, Mao XO, Banwait S, DerMardirossian CM, Bokoch GM, Jin K, Greenberg DA: Regulation of hypoxic neuronal death signaling by neuroglobin. FASEB J 2008, 22(6):1737-1747.
  • [11]Yu Z, Fan X, Lo EH, Wang X: Neuroprotective roles and mechanisms of neuroglobin. Neurol Res 2009, 31(2):122-127.
  • [12]Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, Dixon CE, Fini ME, Lo EH: Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 2000, 20(18):7037-7042.
  • [13]Lok J, Leung W, Zhao S, Pallast S, van Leyen K, Guo S, Wang X, Yalcin A, Lo EH: gamma-glutamylcysteine ethyl ester protects cerebral endothelial cells during injury and decreases blood-brain barrier permeability after experimental brain trauma. J Neurochem 2011, 118(2):248-255.
  • [14]Sultana R, Butterfield DA: Slot-blot analysis of 3-nitrotyrosine-modified brain proteins. Methods Enzymol 2008, 440:309-316.
  • [15]Deng Y, Thompson BM, Gao X, Hall ED: Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury. Exp Neurol 2007, 205(1):154-165.
  • [16]Tsenter J, Beni-Adani L, Assaf Y, Alexandrovich AG, Trembovler V, Shohami E: Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions. J Neurotrauma 2008, 25(4):324-333.
  • [17]Beni-Adani L, Gozes I, Cohen Y, Assaf Y, Steingart RA, Brenneman DE, Eizenberg O, Trembolver V, Shohami E: A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice. J Pharmacol Exp Ther 2001, 296(1):57-63.
  • [18]Bermpohl D, You Z, Korsmeyer SJ, Moskowitz MA, Whalen MJ: Traumatic brain injury in mice deficient in Bid: effects on histopathology and functional outcome. J Cereb Blood Flow Metab 2006, 26(5):625-633.
  • [19]Liu N, Yu Z, Xiang S, Zhao S, Tjarnlund-Wolf A, Xing C, Zhang J, Wang X: Transcriptional regulation mechanisms of hypoxia-induced neuroglobin gene expression. Biochem J 2012, 443(1):153-164.
  • [20]Sun Y, Jin K, Peel A, Mao XO, Xie L, Greenberg DA: Neuroglobin protects the brain from experimental stroke in vivo. Proc Natl Acad Sci USA 2003, 100(6):3497-3500.
  • [21]Lin X, Li M, Hu YZ, Han ZT, Zhang HH, Shang AJ, Gao DW, Zhou DB: An experimental research of neuroglobin expression changes and neural apoptosis after traumatic brain injury. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2010, 26(1):39-44.
  • [22]Chuang PY, Conley YP, Poloyac SM, Okonkwo DO, Ren D, Sherwood PR, Hravnak M, Alexander SA: Neuroglobin genetic polymorphisms and their relationship to functional outcomes after traumatic brain injury. J Neurotrauma 2010, 27(6):999-1006.
  • [23]Shang A, Liu K, Wang H, Wang J, Hang X, Yang Y, Wang Z, Zhang C, Zhou D: Neuroprotective effects of neuroglobin after mechanical injury. Neurol Sci 2012, 33(3):551-558.
  • [24]Jain KK: Neuroprotection in traumatic brain injury. Drug Discov Today 2008, 13(23–24):1082-1089.
  • [25]Dirnagl U, Simon RP, Hallenbeck JM: Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 2003, 26(5):248-254.
  • [26]Wei X, Yu Z, Cho KS, Chen H, Malik MT, Chen X, Lo EH, Wang X, Chen DF: Neuroglobin is an endogenous neuroprotectant for retinal ganglion cells against glaucomatous damage. Am J Pathol 2011, 179(6):2788-2797.
  • [27]Jin K, Mao XO, Xie L, John V, Greenberg DA: Pharmacological induction of neuroglobin expression. Pharmacology 2011, 87(1–2):81-84.
  • [28]Ansari MA, Roberts KN, Scheff SW: Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radic Biol Med 2008, 45(4):443-452.
  • [29]Hall ED, Detloff MR, Johnson K, Kupina NC: Peroxynitrite-mediated protein nitration and lipid peroxidation in a mouse model of traumatic brain injury. J Neurotrauma 2004, 21(1):9-20.
  • [30]Houdebine LM: The methods to generate transgenic animals and to control transgene expression. J Biotechnol 2002, 98(2–3):145-160.
  • [31]Sijen T, Vijn I, Rebocho A, van Blokland R, Roelofs D, Mol JN, Kooter JM: Transcriptional and posttranscriptional gene silencing are mechanistically related. Curr Biol 2001, 11(6):436-440.
  文献评价指标  
  下载次数:59次 浏览次数:21次