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14-3-3γ and Neuroglobin are New Intrinsic Protective Factors for Cerebral Ischemia

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Abstract

A number of intrinsic factors are present intracellularly and could be turned on to protect cells from stress and injury, including cerebral ischemia. The degree of protection of these factors is dependent on the time of induction, their concentration, as well as the duration and extent of injury. This review summarizes recent studies on some of the protective factors with specific emphasis on two recently discovered intrinsic protective proteins: 14-3-3γ protein and neuroglobin. Both of them were originally discovered in neurons, later identified in astrocytes under ischemic conditions, and demonstrated to have protective effect on nerve cells from apoptosis. Understanding the mode of induction and role of protection of these intrinsic protective proteins would be beneficial for the future development of pharmacotherapy in extending the therapeutic time window, which would lead to better stroke management for patients.

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References

  1. Fisher M, Takano K (1995) The penumbra, therapeutic time window and acute ischaemic stroke. Baillières Clin Neurol 4:279–295

    CAS  PubMed  Google Scholar 

  2. Yao H, Okada Y, Ibayashi S (2002) Therapeutic time window for YAG laser-induced reperfusion of thrombotic stroke in hypertensive rats. NeuroReport 13:1005–1008

    PubMed  Google Scholar 

  3. Kaplan B, Brint S, Tanabe J, Jacewicz M, Wang XJ, Pulsinelli W (1991) Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. Stroke 22:1032–1039

    CAS  PubMed  Google Scholar 

  4. Memezawa H, Smith ML, Siesjo BK (1992) Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke 23:552–559

    CAS  PubMed  Google Scholar 

  5. Baron JC, von Kummer R, del Zoppo GJ (1995) Treatment of acute ischemic stroke. Challenging the concept of a rigid and universal time window. Stroke 26:2219–2221

    CAS  PubMed  Google Scholar 

  6. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    CAS  PubMed  Google Scholar 

  7. Shin JA, Park EM, Choi JS, Seo SM, Kang JL, Lee KE, Cho S (2009) Ischemic preconditioning-induced neuroprotection is associated with differential expression of IL-1beta and IL-1 receptor antagonist in the ischemic cortex. J Neuroimmunol 217:14–19

    CAS  PubMed  Google Scholar 

  8. Kitagawa K, Matsumoto M, Tagaya M, Hata R, Ueda H, Niinobe M, Handa N, Fukunaga R, Kimura K, Mikoshiba K et al (1990) 'Ischemic tolerance' phenomenon found in the brain. Brain Res 528:21–24

    CAS  PubMed  Google Scholar 

  9. Shao G, Gong KR, Li J, Xu XJ, Gao CY, Zeng XZ, Lu GW, Huo X (2009) Antihypoxic effects of neuroglobin in hypoxia-preconditioned mice and SH-SY5Y cells. Neurosignals 17:196–202

    CAS  PubMed  Google Scholar 

  10. Murray CJ, Lopez AD (1997) Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 349:1269–1276

    CAS  PubMed  Google Scholar 

  11. Hankey GJ, Jamrozik K, Broadhurst RJ, Forbes S, Burvill PW, Anderson CS, Stewart-Wynne EG (2000) Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study. Stroke 31:2080–2086

    CAS  PubMed  Google Scholar 

  12. Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ (2007) Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol 6:456–464

    PubMed  Google Scholar 

  13. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH et al (1995) Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 274:1017–1025

    CAS  PubMed  Google Scholar 

  14. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995). N Engl J Med 333:1581–1587

    Google Scholar 

  15. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S (2004) Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 363:768–774

    PubMed  Google Scholar 

  16. CAST (Chinese Acute Stroke Trial) Collaborative Group (1997) CAST: randomised placebo-controlled trial of early aspirin use in 20, 000 patients with acute ischaemic stroke. Lancet 349:1641–1649

    Google Scholar 

  17. International Stroke Trial Collaborative Group (1997) The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet 349:1569–1581

    Google Scholar 

  18. Gilligan AK, Thrift AG, Sturm JW, Dewey HM, Macdonell RA, Donnan GA (2005) Stroke units, tissue plasminogen activator, aspirin and neuroprotection: which stroke intervention could provide the greatest community benefit? Cerebrovasc Dis 20:239–244

    CAS  PubMed  Google Scholar 

  19. Wahlgren N, Ahmed N, Davalos A, Hacke W, Millan M, Muir K, Roine RO, Toni D, Lees KR (2008) Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 372:1303–1309

    CAS  PubMed  Google Scholar 

  20. Lyden P (2008) Thrombolytic therapy for acute stroke—not a moment to lose. N Engl J Med 359:1393–1395

    CAS  PubMed  Google Scholar 

  21. Janoff A (1964) Alterations in lysosomes (intracellular enzymes) during shock; effects of preconditioning (tolerance) and protective drugs. Int Anesthesiol Clin 2:251–269

    CAS  PubMed  Google Scholar 

  22. Bazan NG, Palacios-Pelaez R, Lukiw WJ (2002) Hypoxia signaling to genes: significance in Alzheimer's disease. Mol Neurobiol 26:283–298

    CAS  PubMed  Google Scholar 

  23. Brown CM, Suzuki S, Jelks KA, Wise PM (2009) Estradiol is a potent protective, restorative, and trophic factor after brain injury. Semin Reprod Med 27:240–249

    CAS  PubMed  Google Scholar 

  24. Chen XQ, Chen JG, Zhang Y, Hsiao WW, Yu AC (2003) 14-3-3gamma is upregulated by in vitro ischemia and binds to protein kinase Raf in primary cultures of astrocytes. Glia 42:315–324

    CAS  PubMed  Google Scholar 

  25. Steiger HJ, Hanggi D (2007) Ischaemic preconditioning of the brain, mechanisms and applications. Acta Neurochir (Wien) 149:1–10

    Google Scholar 

  26. Kiessling M, Gass P (1993) Immediate early gene expression in experimental epilepsy. Brain Pathol 3:381–393

    CAS  PubMed  Google Scholar 

  27. Nitta-Komatsubara Y, Abe K, Aoki M, Isoyama S (2000) Altered ischemic induction of immediate early gene and heat shock protein 70 mRNAs after preconditioning in rat hearts. Life Sci 66:1261–1270

    CAS  PubMed  Google Scholar 

  28. Kawahara N, Wang Y, Mukasa A, Furuya K, Shimizu T, Hamakubo T, Aburatani H, Kodama T, Kirino T (2004) Genome-wide gene expression analysis for induced ischemic tolerance and delayed neuronal death following transient global ischemia in rats. J Cereb Blood Flow Metab 24:212–223

    CAS  PubMed  Google Scholar 

  29. Tang Y, Pacary E, Freret T, Divoux D, Petit E, Schumann-Bard P, Bernaudin M (2006) Effect of hypoxic preconditioning on brain genomic response before and following ischemia in the adult mouse: identification of potential neuroprotective candidates for stroke. Neurobiol Dis 21:18–28

    CAS  PubMed  Google Scholar 

  30. Liu HM, Li JX, Chen LB (2007) Ischemic preconditioning relieves ischemia/reperfusion injury of hippocampus neurons in rat by inhibiting p53 and bax expressions. Chin Med Sci J 22:123–127

    CAS  PubMed  Google Scholar 

  31. Liu J, Narasimhan P, Yu F, Chan PH (2005) Neuroprotection by hypoxic preconditioning involves oxidative stress-mediated expression of hypoxia-inducible factor and erythropoietin. Stroke 36:1264–1269

    CAS  PubMed  Google Scholar 

  32. Albers GW, Caplan LR, Easton JD, Fayad PB, Mohr JP, Saver JL, Sherman DG (2002) Transient ischemic attack—proposal for a new definition. N Engl J Med 347:1713–1716

    PubMed  Google Scholar 

  33. Zsuga J, Gesztelyi R, Juhasz B, Kemeny-Beke A, Fekete I, Csiba L, Bereczki D (2008) Prior transient ischemic attack is independently associated with lesser in-hospital case fatality in acute stroke. Psychiatry Clin Neurosci 62:705–712

    PubMed  Google Scholar 

  34. Schaller B (2005) Ischemic preconditioning as induction of ischemic tolerance after transient ischemic attacks in human brain: its clinical relevance. Neurosci Lett 377:206–211

    CAS  PubMed  Google Scholar 

  35. Wegener S, Gottschalk B, Jovanovic V, Knab R, Fiebach JB, Schellinger PD, Kucinski T, Jungehulsing GJ, Brunecker P, Muller B, Banasik A, Amberger N, Wernecke KD, Siebler M, Rother J, Villringer A, Weih M (2004) Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke 35:616–621

    PubMed  Google Scholar 

  36. Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT (2006) Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375:727–734

    Google Scholar 

  37. Does remote ischaemic preconditioning reduce heart and cerebral damage following carotid endarterectomy? A randomised controlled trial. [cited 2009 Feb 13]; Available from: http://www.controlled-trials.com/ISRCTN98544942

  38. Treating patients with aneurysmal subarachnoid hemorrhage (SAH) with epoetin alfa (EPO). [cited 2009 Feb 13]; Available from: http://clinicaltrials.gov/ct2/show/NCT00626574

  39. Birkle DL, Bazan NG (1987) Effect of bicuculline-induced status epilepticus on prostaglandins and hydroxyeicosatetraenoic acids in rat brain subcellular fractions. J Neurochem 48:1768–1778

    CAS  PubMed  Google Scholar 

  40. Zhong B, Wang DH (2008) N-oleoyldopamine, a novel endogenous capsaicin-like lipid, protects the heart against ischemia-reperfusion injury via activation of TRPV1. Am J Physiol Heart Circ Physiol 295:H728–735

    CAS  PubMed  Google Scholar 

  41. Rehni AK, Singh N, Jaggi AS (2007) Possible involvement of insulin, endogenous opioids and calcitonin gene-related peptide in remote ischaemic preconditioning of the brain. Yakugaku Zasshi 127:1013–1020

    PubMed  Google Scholar 

  42. Traub ML, De Butte-Smith M, Suzanne Zukin R, Etgen AM (2009) Oestradiol and IGF1 reduce cell loss after global ischemia in middle-aged female rats. J Neuroendocrinol 21:1038–1044

    Google Scholar 

  43. Tixier E, Leconte C, Touzani O, Roussel S, Petit E, Bernaudin M (2008) Adrenomedullin protects neurons against oxygen glucose deprivation stress in an autocrine and paracrine manner. J Neurochem 106:1388–1403

    CAS  PubMed  Google Scholar 

  44. Sayeed I, Stein DG (2009) Progesterone as a neuroprotective factor in traumatic and ischemic brain injury. Prog Brain Res 175:219–237

    CAS  PubMed  Google Scholar 

  45. Matejovska I, Bernaskova K, Krysl D, Mares J (2008) Influence of melatonin pretreatment and preconditioning by hypobaric hypoxia on the development of cortical photothrombotic ischemic lesion. Physiol Res 57:283–288

    CAS  PubMed  Google Scholar 

  46. Doyle KP, Suchland KL, Ciesielski TM, Lessov NS, Grandy DK, Scanlan TS, Stenzel-Poore MP (2007) Novel thyroxine derivatives, thyronamine and 3-iodothyronamine, induce transient hypothermia and marked neuroprotection against stroke injury. Stroke 38:2569–2576

    CAS  PubMed  Google Scholar 

  47. Rami A, Bechmann I, Stehle JH (2008) Exploiting endogenous anti-apoptotic proteins for novel therapeutic strategies in cerebral ischemia. Prog Neurobiol 85:273–296

    CAS  PubMed  Google Scholar 

  48. Bazan NG (2005) Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol 15:159–166

    CAS  PubMed  Google Scholar 

  49. Bazan NG (2007) Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care 10:136–141

    CAS  PubMed  Google Scholar 

  50. Liu M, Eguchi N, Yamasaki Y, Urade Y, Hattori N, Urabe T (2009) Protective role of hematopoietic prostaglandin D synthase in transient focal cerebral ischemia in mice. Neuroscience 163:296–307

    CAS  PubMed  Google Scholar 

  51. Liu Y, Chen L, Xu X, Vicaut E, Sercombe R (2009) Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2. BMC Physiol 9:17

    PubMed  Google Scholar 

  52. Guo WP, Wang J, Li RX, Peng YW (2006) Neuroprotective effects of neuregulin-1 in rat models of focal cerebral ischemia. Brain Res 1087:180–185

    CAS  PubMed  Google Scholar 

  53. Li X, Stark GR (2002) NFkappaB-dependent signaling pathways. Exp Hematol 30:285–296

    CAS  PubMed  Google Scholar 

  54. Duckworth EA, Butler T, Collier L, Collier S, Pennypacker KR (2006) NF-kappaB protects neurons from ischemic injury after middle cerebral artery occlusion in mice. Brain Res 1088:167–175

    CAS  PubMed  Google Scholar 

  55. Nijboer CH, Heijnen CJ, Groenendaal F, May MJ, van Bel F, Kavelaars A (2008) Strong neuroprotection by inhibition of NF-kappaB after neonatal hypoxia-ischemia involves apoptotic mechanisms but is independent of cytokines. Stroke 39:2129–2137

    CAS  PubMed  Google Scholar 

  56. Nijboer CH, Heijnen CJ, Groenendaal F, May MJ, van Bel F, Kavelaars A (2008) A dual role of the NF-kappaB pathway in neonatal hypoxic-ischemic brain damage. Stroke 39:2578–2586

    CAS  PubMed  Google Scholar 

  57. Blondeau N, Widmann C, Lazdunski M, Heurteaux C (2001) Activation of the nuclear factor-kappaB is a key event in brain tolerance. J Neurosci 21:4668–4677

    CAS  PubMed  Google Scholar 

  58. Ran R, Xu H, Lu A, Bernaudin M, Sharp FR (2005) Hypoxia preconditioning in the brain. Dev Neurosci 27:87–92

    CAS  PubMed  Google Scholar 

  59. O'Rourke JF, Dachs GU, Gleadle JM, Maxwell PH, Pugh CW, Stratford IJ, Wood SM, Ratcliffe PJ (1997) Hypoxia response elements. Oncol Res 9:327–332

    PubMed  Google Scholar 

  60. Sharp FR, Ran R, Lu A, Tang Y, Strauss KI, Glass T, Ardizzone T, Bernaudin M (2004) Hypoxic preconditioning protects against ischemic brain injury. NeuroRx 1:26–35

    PubMed  Google Scholar 

  61. Liu R, Suzuki A, Guo Z, Mizuno Y, Urabe T (2006) Intrinsic and extrinsic erythropoietin enhances neuroprotection against ischemia and reperfusion injury in vitro. J Neurochem 96:1101–1110

    CAS  PubMed  Google Scholar 

  62. Grimm C, Wenzel A, Acar N, Keller S, Seeliger M, Gassmann M (2006) Hypoxic preconditioning and erythropoietin protect retinal neurons from degeneration. Adv Exp Med Biol 588:119–131

    PubMed  Google Scholar 

  63. Du Y, Li C, Hu WW, Song YJ, Zhang GY (2009) Neuroprotection of preconditioning against ischemic brain injury in rat hippocampus through inhibition of the assembly of GluR6-PSD95-mixed lineage kinase 3 signaling module via nuclear and non-nuclear pathways. Neuroscience 161:370–380

    CAS  PubMed  Google Scholar 

  64. Chen XQ, Qin LY, Zhang CG, Yang LT, Gao Z, Liu S, Lau LT, Fung YW, Greenberg DA, Yu AC (2005) Presence of neuroglobin in cultured astrocytes. Glia 50:182–186

    PubMed  Google Scholar 

  65. Chen XQ, Yu AC (2002) The association of 14-3-3gamma and actin plays a role in cell division and apoptosis in astrocytes. Biochem Biophys Res Commun 296:657–663

    PubMed  Google Scholar 

  66. Moore BW, Perez VJ (1967) Specific acid proteins in nervous system. In: Carlson FD (ed) Physiological and biochemical aspects of nervous intergration. Prentice-Hall, Englewood Cliffs, pp 343–359

    Google Scholar 

  67. Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647

    CAS  PubMed  Google Scholar 

  68. Masters SC, Fu H (2001) 14-3-3 proteins mediate an essential anti-apoptotic signal. J Biol Chem 276:45193–45200

    CAS  PubMed  Google Scholar 

  69. Pirim I (1998) Ischemic rat brains contain immunoreactivity of 14-3-3 proteins. Int J Neurosci 95:101–106

    CAS  PubMed  Google Scholar 

  70. Jang SW, Liu X, Fu H, Rees H, Yepes M, Levey A, Ye K (2009) Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons. J Biol Chem 284:24512–24525

    CAS  PubMed  Google Scholar 

  71. Chen XQ, Fung YW, Yu AC (2005) Association of 14-3-3gamma and phosphorylated bad attenuates injury in ischemic astrocytes. J Cereb Blood Flow Metab 25:338–347

    CAS  PubMed  Google Scholar 

  72. Dong Y, Liu HD, Zhao R, Yang CZ, Chen XQ, Wang XH, Lau LT, Chen J, Yu AC (2009) Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3gamma in astrocyte. J Neurochem 109(Suppl 1):182–188

    CAS  PubMed  Google Scholar 

  73. Yu AC, Wong HK, Yung HW, Lau LT (2001) Ischemia-induced apoptosis in primary cultures of astrocytes. Glia 35:121–130

    CAS  PubMed  Google Scholar 

  74. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ (1996) Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 87:619–628

    CAS  PubMed  Google Scholar 

  75. Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC (1999) Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 284:339–343

    CAS  PubMed  Google Scholar 

  76. Su QJ, Chen XW, Chen ZB, Sun SG (2008) Involvement of ERK1/2 and p38 MAPK in up-regulation of 14-3-3 protein induced by hydrogen peroxide preconditioning in PC12 cells. Neurosci Bull 24:244–250

    CAS  PubMed  Google Scholar 

  77. Kawamoto Y, Akiguchi I, Tomimoto H, Shirakashi Y, Honjo Y, Budka H (2006) Upregulated expression of 14-3-3 proteins in astrocytes from human cerebrovascular ischemic lesions. Stroke 37:830–835

    CAS  PubMed  Google Scholar 

  78. Fujii K, Tanabe Y, Kobayashi K, Uchikawa H, Kohno Y (2005) Detection of 14-3-3 protein in the cerebrospinal fluid in mitochondrial encephalopathy with lactic acidosis and stroke-like episodes. J Neurol Sci 239:115–118

    CAS  PubMed  Google Scholar 

  79. Siman R, McIntosh TK, Soltesz KM, Chen Z, Neumar RW, Roberts VL (2004) Proteins released from degenerating neurons are surrogate markers for acute brain damage. Neurobiol Dis 16:311–320

    CAS  PubMed  Google Scholar 

  80. Umahara T, Uchihara T, Tsuchiya K, Nakamura A, Iwamoto T (2007) Intranuclear localization and isoform-dependent translocation of 14-3-3 proteins in human brain with infarction. J Neurol Sci 260:159–166

    CAS  PubMed  Google Scholar 

  81. Satoh J, Tabunoki H, Nanri Y, Arima K, Yamamura T (2006) Human astrocytes express 14-3-3 sigma in response to oxidative and DNA-damaging stresses. Neurosci Res 56:61–72

    CAS  PubMed  Google Scholar 

  82. Chen XQ, Liu S, Qin LY, Wang CR, Fung YW, Yu AC (2005) Selective regulation of 14-3-3eta in primary culture of cerebral cortical neurons and astrocytes during development. J Neurosci Res 79:114–118

    CAS  PubMed  Google Scholar 

  83. Wu JS, Cheung WM, Tsai YS, Chen YT, Fong WH, Tsai HD, Chen YC, Liou JY, Shyue SK, Chen JJ, Chen YE, Maeda N, Wu KK, Lin TN (2009) Ligand-activated peroxisome proliferator-activated receptor-gamma protects against ischemic cerebral infarction and neuronal apoptosis by 14-3-3 epsilon upregulation. Circulation 119:1124–1134

    CAS  PubMed  Google Scholar 

  84. Yang C, Ren Y, Liu F, Cai W, Zhang N, Nagel DJ, Yin G (2008) Ischemic preconditioning suppresses apoptosis of rabbit spinal neurocytes by inhibiting ASK1-14-3-3 dissociation. Neurosci Lett 441:267–271

    CAS  PubMed  Google Scholar 

  85. Chen HP, He M, Xu YL, Huang QR, Zeng GH, Liu D, Liao ZP (2007) Anoxic preconditioning up-regulates 14-3-3 protein expression in neonatal rat cardiomyocytes through extracellular signal-regulated protein kinase 1/2. Life Sci 81:372–379

    CAS  PubMed  Google Scholar 

  86. Burmester T, Weich B, Reinhardt S, Hankeln T (2000) A vertebrate globin expressed in the brain. Nature 407:520–523

    CAS  PubMed  Google Scholar 

  87. Merx MW, Flogel U, Stumpe T, Godecke A, Decking UK, Schrader J (2001) Myoglobin facilitates oxygen diffusion. FASEB J 15:1077–1079

    CAS  PubMed  Google Scholar 

  88. Kriegl JM, Bhattacharyya AJ, Nienhaus K, Deng P, Minkow O, Nienhaus GU (2002) Ligand binding and protein dynamics in neuroglobin. Proc Natl Acad Sci U S A 99:7992–7997

    CAS  PubMed  Google Scholar 

  89. Sun Y, Jin K, Peel A, Mao XO, Xie L, Greenberg DA (2003) Neuroglobin protects the brain from experimental stroke in vivo. Proc Natl Acad Sci U S A 100:3497–3500

    CAS  PubMed  Google Scholar 

  90. Khan AA, Wang Y, Sun Y, Mao XO, Xie L, Miles E, Graboski J, Chen S, Ellerby LM, Jin K, Greenberg DA (2006) Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia. Proc Natl Acad Sci U S A 103:17944–17948

    CAS  PubMed  Google Scholar 

  91. Jin K, Mao Y, Mao X, Xie L, Greenberg DA (2010) Neuroglobin expression in ischemic stroke. Stroke 41:557–559

    CAS  PubMed  Google Scholar 

  92. Gabriel C, Ali C, Lesne S, Fernandez-Monreal M, Docagne F, Plawinski L, MacKenzie ET, Buisson A, Vivien D (2003) Transforming growth factor alpha-induced expression of type 1 plasminogen activator inhibitor in astrocytes rescues neurons from excitotoxicity. FASEB J 17:277–279

    CAS  PubMed  Google Scholar 

  93. Yang LT, Gao Z, Li HL, Lu J, Yu AC (2007) Neuroglobin but not cytoglobin binds specifically to mitochondria in neural cells. In the 7th Biennial Meeting and the 5th Congress of the Chinese Society for Neuroscience of Conference. Hangzhou, China: Springer Verlag. 23:387–388

  94. Flogel U, Merx MW, Godecke A, Decking UK, Schrader J (2001) Myoglobin: a scavenger of bioactive NO. Proc Natl Acad Sci U S A 98:735–740

    CAS  PubMed  Google Scholar 

  95. Ligon LA, Steward O (2000) Movement of mitochondria in the axons and dendrites of cultured hippocampal neurons. J Comp Neurol 427:340–350

    CAS  PubMed  Google Scholar 

  96. Ye SQ, Zhou XY, Lai XJ, Zheng L, Chen XQ (2009) Silencing neuroglobin enhances neuronal vulnerability to oxidative injury by down-regulating 14-3-3gamma. Acta Pharmacol Sin 30:913–918

    CAS  PubMed  Google Scholar 

  97. Sevimli S, Diederich K, Strecker JK, Schilling M, Klocke R, Nikol S, Kirsch F, Schneider A, Schabitz WR (2009) Endogenous brain protection by granulocyte-colony stimulating factor after ischemic stroke. Exp Neurol 217:328–335

    CAS  PubMed  Google Scholar 

  98. Ma YP, Ma MM, Cheng SM, Ma HH, Yi XM, Xu GL, Liu XF (2008) Intranasal bFGF-induced progenitor cell proliferation and neuroprotection after transient focal cerebral ischemia. Neurosci Lett 437:93–97

    CAS  PubMed  Google Scholar 

  99. Roitbak T, Li L, Cunningham LA (2008) Neural stem/progenitor cells promote endothelial cell morphogenesis and protect endothelial cells against ischemia via HIF-1alpha-regulated VEGF signaling. J Cereb Blood Flow Metab 28:1530–1542

    CAS  PubMed  Google Scholar 

  100. Chang YC, Shyu WC, Lin SZ, Li H (2007) Regenerative therapy for stroke. Cell Transplant 16:171–181

    PubMed  Google Scholar 

  101. Siliprandi R, Canella R, Carmignoto G (1993) Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia. Invest Ophthalmol Vis Sci 34:3232–3245

    CAS  PubMed  Google Scholar 

  102. Yoo JY, Won YJ, Lee JH, Kim JU, Sung IY, Hwang SJ, Kim MJ, Hong HN (2009) Neuroprotective effects of erythropoietin posttreatment against kainate-induced excitotoxicity in mixed spinal cultures. J Neurosci Res 87:150–163

    CAS  PubMed  Google Scholar 

  103. Weber AJ, Harman CD, Viswanathan S (2008) Effects of optic nerve injury, glaucoma, and neuroprotection on the survival, structure, and function of ganglion cells in the mammalian retina. J Physiol 586:4393–4400

    CAS  PubMed  Google Scholar 

  104. Marciniak K, Butwicka A, Nowak JZ (2006) PEDF: an endogenous factor displaying potent neuroprotective, neurotrophic, and antiangiogenic activity. Postepy Hig Med Dosw (Online) 60:387–396

    Google Scholar 

  105. Parrilla-Reverter G, Agudo M, Sobrado-Calvo P, Salinas-Navarro M, Villegas-Perez MP, Vidal-Sanz M (2009) Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: a quantitative in vivo study. Exp Eye Res 89:32–41

    CAS  PubMed  Google Scholar 

  106. Li J, Qu Y, Li X, Li D, Zhao F, Mao M, Ferriero D, Mu D (2010) The role of integrin alpha(v)beta (8) in neonatal hypoxic-ischemic brain injury. Neurotox Res 17:406–417

    Google Scholar 

  107. Lin CH, Cheng FC, Lu YZ, Chu LF, Wang CH, Hsueh CM (2006) Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors. Exp Neurol 201:225–233

    CAS  PubMed  Google Scholar 

  108. Meucci O, Fatatis A, Simen AA, Miller RJ (2000) Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc Natl Acad Sci U S A 97:8075–8080

    CAS  PubMed  Google Scholar 

  109. Whitlock NA, Agarwal N, Ma JX, Crosson CE (2005) Hsp27 upregulation by HIF-1 signaling offers protection against retinal ischemia in rats. Invest Ophthalmol Vis Sci 46:1092–1098

    PubMed  Google Scholar 

  110. Yi JH, Park SW, Kapadia R, Vemuganti R (2007) Role of transcription factors in mediating post-ischemic cerebral inflammation and brain damage. Neurochem Int 50:1014–1027

    CAS  PubMed  Google Scholar 

  111. Rybnikova E, Glushchenko T, Tyulkova E, Baranova K, Samoilov M (2009) Mild hypobaric hypoxia preconditioning up-regulates expression of transcription factors c-Fos and NGFI-A in rat neocortex and hippocampus. Neurosci Res 65:360–366

    Google Scholar 

  112. Ouk T, Laprais M, Bastide M, Mostafa K, Gautier S, Bordet R (2009) Withdrawal of fenofibrate treatment partially abrogates preventive neuroprotection in stroke via loss of vascular protection. Vascul Pharmacol 51:323–330

    Google Scholar 

  113. Zhao X, Strong R, Zhang J, Sun G, Tsien JZ, Cui Z, Grotta JC, Aronowski J (2009) Neuronal PPARgamma deficiency increases susceptibility to brain damage after cerebral ischemia. J Neurosci 29:6186–6195

    CAS  PubMed  Google Scholar 

  114. Fan X, Heijnen CJ, van der Kooij MA, Groenendaal F, van Bel F (2009) The role and regulation of hypoxia-inducible factor-1alpha expression in brain development and neonatal hypoxic-ischemic brain injury. Brain Res Rev 62:99–108

    Google Scholar 

  115. Chan PH (1994) Oxygen radicals in focal cerebral ischemia. Brain Pathol 4:59–65

    Article  CAS  PubMed  Google Scholar 

  116. Desagher S, Glowinski J, Premont J (1996) Astrocytes protect neurons from hydrogen peroxide toxicity. J Neurosci 16:2553–2562

    CAS  PubMed  Google Scholar 

  117. Kelley MH, Taguchi N, Ardeshiri A, Kuroiwa M, Hurn PD, Traystman RJ, Herson PS (2008) Ischemic insult to cerebellar Purkinje cells causes diminished GABAA receptor function and allopregnanolone neuroprotection is associated with GABAA receptor stabilization. J Neurochem 107:668–678

    CAS  PubMed  Google Scholar 

  118. Solaroglu I, Jadhav V, Zhang JH (2007) Neuroprotective effect of granulocyte-colony stimulating factor. Front Biosci 12:712–724

    CAS  PubMed  Google Scholar 

  119. Sadasivan S, Maher TJ, Quang LS (2006) Gamma-Hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and 1, 4-butanediol (1, 4-BD) reduce the volume of cerebral infarction in rodent transient middle cerebral artery occlusion. Ann N Y Acad Sci 1074:537–544

    CAS  PubMed  Google Scholar 

  120. Salazar-Colocho P, Del Rio J, Frechilla D (2008) Neuroprotective effects of serotonin 5-HT 1A receptor activation against ischemic cell damage in gerbil hippocampus: involvement of NMDA receptor NR1 subunit and BDNF. Brain Res 1199:159–166

    CAS  PubMed  Google Scholar 

  121. Molina-Holgado F, Pinteaux E, Moore JD, Molina-Holgado E, Guaza C, Gibson RM, Rothwell NJ (2003) Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 23:6470–6474

    CAS  PubMed  Google Scholar 

  122. Pinteaux E, Rothwell NJ, Boutin H (2006) Neuroprotective actions of endogenous interleukin-1 receptor antagonist (IL-1ra) are mediated by glia. Glia 53:551–556

    PubMed  Google Scholar 

  123. Li RC, Morris MW, Lee SK, Pouranfar F, Wang Y, Gozal D (2008) Neuroglobin protects PC12 cells against oxidative stress. Brain Res 1190:159–166

    CAS  PubMed  Google Scholar 

  124. Sinor AD, Irvin SM, Greenberg DA (2000) Endocannabinoids protect cerebral cortical neurons from in vitro ischemia in rats. Neurosci Lett 278:157–160

    CAS  PubMed  Google Scholar 

  125. Sweeney MI (1997) Neuroprotective effects of adenosine in cerebral ischemia: window of opportunity. Neurosci Biobehav Rev 21:207–217

    CAS  PubMed  Google Scholar 

  126. Ouyang YB, Giffard RG (2004) Cellular neuroprotective mechanisms in cerebral ischemia: Bcl-2 family proteins and protection of mitochondrial function. Cell Calcium 36:303–311

    CAS  PubMed  Google Scholar 

  127. Franklin TB, Krueger-Naug AM, Clarke DB, Arrigo AP, Currie RW (2005) The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system. Int J Hyperthermia 21:379–392

    CAS  PubMed  Google Scholar 

  128. Andine P, Lehmann A, Ellren K, Wennberg E, Kjellmer I, Nielsen T, Hagberg H (1988) The excitatory amino acid antagonist kynurenic acid administered after hypoxic-ischemia in neonatal rats offers neuroprotection. Neurosci Lett 90:208–212

    CAS  PubMed  Google Scholar 

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Acknowledgement

We would like to thank Elaine Young, Nelly Lam, and Kinnie Ho from Hai Kang Life Corporation Limited for their assistance in preparation of this manuscript. This work was supported by the National Natural Science Foundation of China (30270426, 30470543, 30670644, 30870818), the Beijing Natural Science Foundation (7032026, 7051004, 7091004), and the National High Technology Research and Development Program of China (863 Program, 2006AA02Z452).

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Authors and Affiliations

  1. Neuroscience Research Institute, Peking University, 38 Xue Yuan Road, Beijing, 100191, China

    Yan Dong, Rui Zhao & Albert Cheung Hoi Yu

  2. Key Laboratory of Neuroscience, Peking University, Ministry of Education, 38 Xue Yuan Road, Beijing, 100191, China

    Yan Dong, Rui Zhao & Albert Cheung Hoi Yu

  3. Key Laboratory for Neuroscience, Peking University, Ministry of Public Health, 38 Xue Yuan Road, Beijing, 100191, China

    Yan Dong, Rui Zhao & Albert Cheung Hoi Yu

  4. Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, 38 Xue Yuan Road, Beijing, 100191, China

    Yan Dong, Rui Zhao & Albert Cheung Hoi Yu

  5. Key Laboratory of Neurological Diseases, Huazhong University of Science and Technology, Ministry of Education, 13 Hang Kong Road, Wuhan, 400030, China

    Xiao Qian Chen

  6. Infectious Disease Center, Peking University, 38 Xue Yuan Road, Beijing, 100191, China

    Albert Cheung Hoi Yu

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  1. Yan Dong
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  2. Rui Zhao
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Correspondence to Albert Cheung Hoi Yu.

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Dong, Y., Zhao, R., Chen, X.Q. et al. 14-3-3γ and Neuroglobin are New Intrinsic Protective Factors for Cerebral Ischemia. Mol Neurobiol 41, 218–231 (2010). https://doi.org/10.1007/s12035-010-8142-4

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