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Hypoxic Preconditioning in the CNS

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Innate Tolerance in the CNS

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

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Abstract

It is now well established that preconditioning the CNS with a variety of stressors can provide neuroprotection from stroke, subarachnoid and intracerebral hemorrhage, epilepsy, and trauma. However, it often remains unstated, and underappreciated, that the resultant ischemic tolerance involves more than just “neuroprotection” but likely involves primary and secondary cytoprotective responses on the part of all cells that comprise the neurovascular unit. This chapter reviews the evidence and molecular mechanisms that underlie vascular endothelial and smooth muscle cell responses to preconditioning, reflected by reductions in postischemic vascular inflammation, blood-brain barrier breakdown, and apoptotic death, along with the improvements in ischemic and postischemic blood flow, vascular reactivity, endothelium-dependent dilation, and other postischemic autoregulatory responses, which together promote an ischemia-tolerant cerebrovasculature. Angiogenesis and other longer-term mechanisms of vascular remodeling and recovery are also likely to contribute. In addition, data supporting the involvement of astrocytes, microglia, and oligodendrocytes in the globally cerebroprotective response to preconditioning, while still relatively limited to date, are examined. Overall, emerging findings suggest both autocrine and paracrine adaptive responses to preconditioning among the neurovascular unit and glial lineage cells that collectively contribute to reductions in lesion size and injury severity in several CNS pathologies.

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References

  • Alkan T, Goren B, Vatansever E, Sarandol E (2008) Effects of hypoxic preconditioning in antioxidant enzyme activities in hypoxic-ischemic brain damage in immature rats. Turk Neurosurg 18:165–171

    PubMed  Google Scholar 

  • Ara J, Fekete S, Frank M, Golden JA, Pleasure D, Valencia I (2011) Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain. Neurobiol Dis 43:473–485

    Article  PubMed  CAS  Google Scholar 

  • Aragones J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, Harten SK, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170–180

    Article  PubMed  CAS  Google Scholar 

  • Aragones J, Fraisl P, Baes M, Carmeliet P (2009) Oxygen sensors at the crossroad of metabolism. Cell Metab 9:11–22

    Article  PubMed  CAS  Google Scholar 

  • Arthur PG, Lim SC, Meloni BP, Munns SE, Chan A, Knuckey NW (2004) The protective effect of hypoxic preconditioning on cortical neuronal cultures is associated with increases in the activity of several antioxidant enzymes. Brain Res 1017:146–154

    Article  PubMed  CAS  Google Scholar 

  • Bailey DM, Taudorf S, Berg RMG, Lundby C, Pedersen BK, Rasmussen P, Moller K (2011) Cerebral formation of free radicals during hypoxia does not cause structural damage and is associated with a reduction in mitochondrial PO2; evidence of O2-sensing in humans? J Cereb Blood Flow Metab 31:1020–1026

    Article  PubMed  CAS  Google Scholar 

  • Baranova O, Miranda LF, Pichiule P, Dragatsis I, Johnson RS, Chavez JC (2007) Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci 27:6320–6332

    Article  PubMed  CAS  Google Scholar 

  • Bergeron M, Gidday JM, Yu AY, Semenza GL, Ferriero DM, Sharp FR (2000) Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Ann Neurol 48:285–296

    Article  PubMed  CAS  Google Scholar 

  • Bernaudin M, Bellail A, Marti HH, Yvon A, Vivien D, Duchatelle I, Mackenzie ET, Petit E (2000) Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain. Glia 30:271–278

    Article  PubMed  CAS  Google Scholar 

  • Bernaudin M, Nedelec AS, Divoux D, MacKenzie ET, Petit E, Schumann-Bard P (2002a) Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain. J Cereb Blood Flow Metab 22:393–403

    Article  PubMed  CAS  Google Scholar 

  • Bernaudin M, Tang Y, Reilly M, Petit E, Sharp FR (2002b) Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. J Biol Chem 277:39728–39738

    Article  PubMed  CAS  Google Scholar 

  • Bickler PE, Fahlman CS (2009) Expression of signal transduction genes differs after hypoxic or isoflurane preconditioning of rat hippocampal slice cultures. Anesthesiology 111:258–266

    Article  PubMed  CAS  Google Scholar 

  • Bickler PE, Fahlman CS (2010) Enhanced hypoxic preconditioning by isoflurane: signaling gene expression and requirement of intracellular Ca2+ and inositol triphosphate receptors. Brain Res 1340:86–95

    Article  PubMed  CAS  Google Scholar 

  • Bickler PE, Fahlman CS, Gray J, McKleroy W (2009) Inositol 1,4,5-triphosphate receptors and NAD(P)H mediate Ca2+ signaling required for hypoxic preconditioning of hippocampal neurons. Neuroscience 160:51–60

    Article  PubMed  CAS  Google Scholar 

  • Bickler PE, Fahlman CS, Gray JJ (2010) Hypoxic preconditioning failure in aging hippocampal neurons: impaired gene expression and rescue with intracellular calcium chelation. J Neurosci Res 88:3520–3529

    Article  PubMed  CAS  Google Scholar 

  • Bruer U, Weih MK, Isaev NK, Meisel A, Ruscher K, Bergk A, Trendelenburg G, Wiegand F, Victorov IV, Dirnagl U (1997) Induction of tolerance in rat cortical neurons: hypoxic preconditioning. FEBS Lett 414:117–121

    Article  PubMed  CAS  Google Scholar 

  • Bu X, Huang P, Qi Z, Zhang N, Han S, Fang L, Li J (2007) Cell type-specific activation of p38 MAPK in the brain regions of hypoxic preconditioned mice. Neurochem Int 51:459–466

    Article  PubMed  CAS  Google Scholar 

  • Bu X, Zhang N, Yang X, Liu Y, Du J, Liang J, Xu Q, Li J (2011) Proteomic analysis of cPKCβII-interacting proteins involved in HPC-induced neuroprotection against cerebral ischemia of mice. J Neurochem 117:346–356

    Article  PubMed  CAS  Google Scholar 

  • Buck LT, Pamenter ME (2006) Adaptive responses of vertebrate neurons to anoxia–matching supply to demand. Respir Physiol Neurobiol 154:226–240

    Article  PubMed  CAS  Google Scholar 

  • Busija DW, Gaspar T, Domoki F, Katakam PV, Bari F (2008) Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning. Adv Drug Deliv Rev 60:1471–1477

    Article  PubMed  CAS  Google Scholar 

  • Chang AY, Wang CH, Chiu TH, Chi JW, Chen CF, Ho LT, Lin AMY (2005) Hypoxic preconditioning attenuated in kainic acid-induced neurotoxicity in rat hippocampus. Exp Neurol 195:40–48

    Article  PubMed  CAS  Google Scholar 

  • Chang K-C, Yang J-J, Liao J-F, Wang C-H, Chiu T-H, Hsu F-C (2006) Chronic hypobaric hypoxia induces tolerance to acute hypoxia and up-regulation in alpha-2 adrenoceptor in rat locus coeruleus. Brain Res 1106:82–90

    Article  PubMed  CAS  Google Scholar 

  • Chavez JC, LaManna JC (2002) Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1. J Neurosci 22:8922–8931

    PubMed  CAS  Google Scholar 

  • Chavez JC, Baranova O, Lin J, Pichiule P (2006) The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygen-dependent expression of erythropoietin in cortical astrocytes. J Neurosci 26:9471–9481

    Article  PubMed  CAS  Google Scholar 

  • Chen Z-Y, Wang L, Asavaritkrai P, Noguchi CT (2010) Up-regulation of erythropoietin receptor by nitric oxide mediates hypoxia preconditioning. J Neurosci Res 88:3180–3188

    Article  PubMed  CAS  Google Scholar 

  • Chu K, Jung K-H, Kim S-J, Lee S-T, Kim J, Park H-K, Song E-C, Kim SU, Kim M, Lee SK, Roh J-K (2008) Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1alpha stabilization in the host brain. Brain Res 1207:182–192

    Article  PubMed  CAS  Google Scholar 

  • Chu PWY, Beart PM, Jones NM (2010) Preconditioning protects against oxidative injury involving hypoxia-inducible factor-1 and vascular endothelial growth factor in cultured astrocytes. Eur J Pharmacol 633:24–32

    Article  PubMed  CAS  Google Scholar 

  • Churilova AV, Rybnikova EA, Glushchenko TS, Tyulkova EI, Samoilov MO (2010) Effects of moderate hypobaric hypoxic preconditioning on the expression of the transcription factors pCREB and NF-kappaB in the rat hippocampus before and after severe hypoxia. Neurosci Behav Physiol 40:852–857

    Article  PubMed  CAS  Google Scholar 

  • Correia SC, Carvalho C, Cardoso S, Santos RX, Santos MS, Oliveira CR, Perry G, Zhu X, Smith MA, Moreira PI (2010) Mitochondrial preconditioning: a potential neuroprotective strategy. Front Aging Neurosci 2:138

    PubMed  Google Scholar 

  • Coulet F, Nadaud S, Agrapart M, Soubrier F (2003) Identification of hypoxia-response element in the human endothelial nitric-oxide synthase gene promoter. J Biol Chem 278:46230–46240

    Article  PubMed  CAS  Google Scholar 

  • Dale-Nagle EA, Hoffman MS, MacFarlane PM, Satriotomo I, Lovett-Barr MR, Vinit S, Mitchell GS (2010) Spinal plasticity following intermittent hypoxia: implications for spinal injury. Ann N Y Acad Sci 1198:252–259

    Article  PubMed  CAS  Google Scholar 

  • Dasgupta N, Patel AM, Scott BA, Crowder CM (2007) Hypoxic preconditioning requires the apoptosis protein CED-4 in C. elegans. Curr Biol 17:1954–1959

    Article  PubMed  CAS  Google Scholar 

  • Dhodda VK, Sailor KA, Bowen KK, Vemuganti R (2004) Putative endogenous mediators of preconditioning-induced ischemic tolerance in rat brain identified by genomic and proteomic analysis. J Neurochem 89:73–89

    Article  PubMed  CAS  Google Scholar 

  • Dirnagl U, Meisel A (2008) Endogenous neuroprotection: mitochondria as gateways to cerebral preconditioning? Neuropharmacology 55:334–344

    Article  PubMed  CAS  Google Scholar 

  • Duan CL, Yan FS, Song XY, Lu GW (1999) Changes of superoxide dismutase, glutathione peroxidase and lipid peroxides in the brain of mice preconditioned by hypoxia. Biol Signals Recept 8:256–260

    Article  PubMed  CAS  Google Scholar 

  • Duszczyk M, Ziembowicz A, Gadamski R, Wieronska JM, Smialowska M, Lazarewicz JW (2009) Changes in the NPY immunoreactivity in gerbil hippocampus after hypoxic and ischemic preconditioning. Neuropeptides 43:31–39

    Article  PubMed  CAS  Google Scholar 

  • Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, Rauter M, Plate K, Sieweke M, Breier G, Flamme I (2003) Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem 278:7520–7530

    Article  PubMed  CAS  Google Scholar 

  • Faeh D, Gutzwiller F, Bopp M (2009) Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation 120:495–501

    Article  PubMed  Google Scholar 

  • Fan Y-y, Hu W-w, Dai H-b, Zhang J-x, Zhang L-y, He P, Shen Y, Ohtsu H, Wei E-q, Chen Z (2011) Activation of the central histaminergic system is involved in hypoxia-induced stroke tolerance in adult mice. J Cereb Blood Flow Metab 31:305–314

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Rhodes PG, Bhatt AJ (2010) Hypoxic preconditioning provides neuroprotection and increases vascular endothelial growth factor A, preserves the phosphorylation of Akt-Ser-473 and diminishes the increase in caspase-3 activity in neonatal rat hypoxic-ischemic model. Brain Res 1325:1–9

    Article  PubMed  CAS  Google Scholar 

  • Francis KR, Wei L (2010) Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis 1:e22

    Article  PubMed  CAS  Google Scholar 

  • Gage AT, Stanton PK (1996) Hypoxia triggers neuroprotective alterations in hippocampal gene expression via a heme-containing sensor. Brain Res 719:172–178

    Article  PubMed  CAS  Google Scholar 

  • Gagnon PM, Simmons DD, Bao J, Lei D, Ortmann AJ, Ohlemiller KK (2007) Temporal and genetic influences on protection against noise-induced hearing loss by hypoxic preconditioning in mice. Hear Res 226:79–91

    Article  PubMed  Google Scholar 

  • Garnier P, Demougeot C, Bertrand N, Prigent-Tessier A, Marie C, Beley A (2001) Stress response to hypoxia in gerbil brain: HO-1 and Mn SOD expression and glial activation. Brain Res 893:301–309

    Article  PubMed  CAS  Google Scholar 

  • Geocadin RG, Malhotra AD, Tong S, Seth A, Moriwaki G, Hanley DF, Thakor NV (2005) Effect of acute hypoxic preconditioning on qEEG and functional recovery after cardiac arrest in rats. Brain Res 1064:146–154

    Article  PubMed  CAS  Google Scholar 

  • Gidday JM, Fitzgibbons JC, Shah AR, Park TS (1994) Neuroprotection from ischemic brain injury by hypoxic preconditioning in the neonatal rat. Neurosci Lett 168:221–224

    Article  PubMed  CAS  Google Scholar 

  • Gidday JM, Shah AR, Maceren RG, Wang Q, Pelligrino DA, Holtzman DM, Park TS (1999) Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning. J Cereb Blood Flow Metab 19:331–340

    Article  PubMed  CAS  Google Scholar 

  • Gorgias N, Maidatsi P, Tsolaki M, Alvanou A, Kiriazis G, Kaidoglou K, Giala M (1996) Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia. Brain Res 714:215–225

    Article  PubMed  CAS  Google Scholar 

  • Grimm C, Wenzel A, Groszer M, Mayser H, Seeliger M, Samardzija M, Bauer C, Gassmann M, Reme CE (2002) HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med 8:718–724

    Article  PubMed  CAS  Google Scholar 

  • Gustavsson M, Anderson MF, Mallard C, Hagberg H (2005) Hypoxic preconditioning confers long-term reduction of brain injury and improvement of neurological ability in immature rats. Pediatr Res 57:305–309

    Article  PubMed  CAS  Google Scholar 

  • Gutsaeva DR, Carraway MS, Suliman HB, Demchenko IT, Shitara H, Yonekawa H, Piantadosi CA (2008) Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism. J Neurosci 28:2015–2024

    Article  PubMed  CAS  Google Scholar 

  • Hamrick SEG, McQuillen PS, Jiang X, Mu D, Madan A, Ferriero DM (2005) A role for hypoxia-inducible factor-1alpha in desferoxamine neuroprotection. Neurosci Lett 379:96–9100

    Article  PubMed  CAS  Google Scholar 

  • Hashiguchi A, Yano S, Morioka M, Hamada J, Ushio Y, Takeuchi Y, Fukunaga K (2004) Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampus. J Cereb Blood Flow Metab 24:271–279

    Article  PubMed  CAS  Google Scholar 

  • He W, Qian Zhong M, Zhu L, Christopher Q, Du F, Yung WH, Ke Y (2008) Ginkgolides mimic the effects of hypoxic preconditioning to protect C6 cells against ischemic injury by up-regulation of hypoxia-inducible factor-1 alpha and erythropoietin. Int J Biochem Cell Biol 40:651–662

    Article  PubMed  CAS  Google Scholar 

  • Hu C-J, Wang L-Y, Chodosh LA, Keith B, Simon MC (2003) Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 23:9361–9374

    Article  PubMed  CAS  Google Scholar 

  • Hu X, Wei L, Taylor TM, Wei J, Zhou X, Wang J-A, Yu SP (2011) Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol 301:362–372

    Article  CAS  Google Scholar 

  • Jaderstad J, Brismar H, Herlenius E (2010) Hypoxic preconditioning increases gap-junctional graft and host communication. Neuroreport 21:1126–1132

    Article  PubMed  Google Scholar 

  • Jiang BH, Jiang G, Zheng JZ, Lu Z, Hunter T, Vogt PK (2001) Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 12:363–369

    PubMed  CAS  Google Scholar 

  • Jones NM, Bergeron M (2001) Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat brain. J Cereb Blood Flow Metab 21:1105–1114

    Article  PubMed  CAS  Google Scholar 

  • Kalpana S, Dhananjay S, Anju B, Lilly G, Sai Ram M (2008) Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat brain: molecular mechanisms of action of cobalt chloride. Toxicol Appl Pharmacol 231:354–363

    Article  PubMed  CAS  Google Scholar 

  • Kenneth NS, Rocha S (2008) Regulation of gene expression by hypoxia. Biochem J 414:19–29

    Article  PubMed  CAS  Google Scholar 

  • Laudenbach V, Fontaine RH, Medja F, Carmeliet P, Hicklin DJ, Gallego J, Leroux P, Marret S, Gressens P (2007) Neonatal hypoxic preconditioning involves vascular endothelial growth factor. Neurobiol Dis 26:243–252

    Article  PubMed  CAS  Google Scholar 

  • Leconte C, Tixier E, Freret T, Toutain J, Saulnier R, Boulouard M, Roussel S, Schumann-Bard P, Bernaudin M (2009) Delayed hypoxic postconditioning protects against cerebral ischemia in the mouse. Stroke 40:3349–3355

    Article  PubMed  Google Scholar 

  • Levin SG, Godukhin OV (2009) Comparative roles of ATP-sensitive K+ channels and Ca2+ -activated BK+ channels in posthypoxic hyperexcitability and rapid hypoxic preconditioning in hippocampal CA1 pyramidal neurons in vitro. Neurosci Lett 461:90–94

    Article  PubMed  CAS  Google Scholar 

  • Levin SG, Shamsutdinova AA, Godukhin OV (2010) Apamin, a selective blocker of SK(Ca) channels, inhibits posthypoxic hyperexcitability but does not affect rapid hypoxic preconditioning in hippocampal CA1 pyramidal neurons in vitro. Neurosci Lett 484:35–38

    Article  PubMed  CAS  Google Scholar 

  • Li J, McCullough LD (2010) Effects of AMP-activated protein kinase in cerebral ischemia. J Cereb Blood Flow Metab 30:480–492

    Article  PubMed  CAS  Google Scholar 

  • Li L, Qu Y, Mao M, Xiong Y, Mu D (2008a) The involvement of phosphoinositide 3-kinase/Akt pathway in the activation of hypoxia-inducible factor-1alpha in the developing rat brain after hypoxia-ischemia. Brain Res 1197:152–158

    Article  PubMed  CAS  Google Scholar 

  • Li Y-X, Ding S-J, Xiao L, Guo W, Zhan Q (2008b) Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1 alpha and erythropoietin. Neurosci Bull 24:89–95

    Article  PubMed  Google Scholar 

  • Lin AMY, Chen CF, Ho LT (2002) Neuroprotective effect of intermittent hypoxia on iron-induced oxidative injury in rat brain. Exp Neurol 176:328–335

    Article  PubMed  CAS  Google Scholar 

  • Lin AMY, Dung S-W, Chen C-F, Chen W-H, Ho L-T (2003) Hypoxic preconditioning prevents cortical infarction by transient focal ischemia-reperfusion. Ann N Y Acad Sci 993:168–178

    Article  PubMed  Google Scholar 

  • Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, Shokat KM, Lavail MM, Walter P (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318:944–949

    Article  PubMed  CAS  Google Scholar 

  • Lin JHC, Lou N, Kang N, Takano T, Hu F, Han X, Xu Q, Lovatt D, Torres A, Willecke K, Yang J, Kang J, Nedergaard M (2008) A central role of connexin 43 in hypoxic preconditioning. J Neurosci 28:681–695

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Ginis I, Spatz M, Hallenbeck JM (2000) Hypoxic preconditioning protects cultured neurons against hypoxic stress via TNF-alpha and ceramide. Am J Physiol Cell Physiol 278:C144–C153

    PubMed  CAS  Google Scholar 

  • Liu L, Wise DR, Diehl JA, Simon MC (2008) Hypoxic reactive oxygen species regulate the integrated stress response and cell survival. J Biol Chem 283:31153–31162

    Article  PubMed  CAS  Google Scholar 

  • Lu GW, Ding DW, Shi MT (1999) Acute adaptation of mice to hypoxic hypoxia. Biol Signals Recept 8:247–255

    Article  PubMed  CAS  Google Scholar 

  • Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40:294–309

    Article  PubMed  CAS  Google Scholar 

  • Mao XR, Crowder CM (2010) Protein misfolding induces hypoxic preconditioning via a subset of the unfolded protein response machinery. Mol Cell Biol 30:5033–5042

    Article  PubMed  CAS  Google Scholar 

  • Marsh B, Stevens SL, Packard AEB, Gopalan B, Hunter B, Leung PY, Harrington CA, Stenzel-Poore MP (2009) Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3. J Neurosci 29:9839–9849

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Romero R, Canuelo A, Martinez-Lara E, Javier Oliver F, Cardenas S, Siles E (2009) Poly(ADP-ribose) polymerase-1 modulation of in vivo response of brain hypoxia-inducible factor-1 to hypoxia/reoxygenation is mediated by nitric oxide and factor inhibiting HIF. J Neurochem 111:150–159

    Article  PubMed  CAS  Google Scholar 

  • Meloni BP, Majda BT, Knuckey NW (2002) Evaluation of preconditioning treatments to protect near-pure cortical neuronal cultures from in vitro ischemia induced acute and delayed neuronal death. Brain Res 928:69–75

    Article  PubMed  CAS  Google Scholar 

  • Miller BA, Perez RS, Shah AR, Gonzales ER, Park TS, Gidday JM (2001) Cerebral protection by hypoxic preconditioning in a murine model of focal ischemia-reperfusion. Neuroreport 12:1663–1669

    Article  PubMed  CAS  Google Scholar 

  • Nalivaeva NN, Fisk L, Kochkina EG, Plesneva SA, Zhuravin IA, Babusikova E, Dobrota D, Turner AJ (2004) Effect of hypoxia/ischemia and hypoxic preconditioning/reperfusion on expression of some amyloid-degrading enzymes. Ann N Y Acad Sci 1035:21–33

    Article  CAS  Google Scholar 

  • Oh JS, Ha Y, An SS, Khan M, Pennant WA, Kim HJ, Yoon DH, Lee M, Kim KN (2010) Hypoxia-preconditioned adipose tissue-derived mesenchymal stem cell increase the survival and gene expression of engineered neural stem cells in a spinal cord injury model. Neurosci Lett 472:215–219

    Article  PubMed  CAS  Google Scholar 

  • Omata N, Murata T, Takamatsu S, Maruoka N, Wada Y, Yonekura Y, Fujibayashi Y (2002) Hypoxic tolerance induction in rat brain slices following hypoxic preconditioning due to expression of neuroprotective proteins as revealed by dynamic changes in glucose metabolism. Neurosci Lett 329:205–208

    Article  PubMed  CAS  Google Scholar 

  • Peng P-H, Huang H-S, Lee Y-J, Chen Y-S, Ma M-C (2009) Novel role for the delta-opioid receptor in hypoxic preconditioning in rat retinas. J Neurochem 108:741–754

    Article  PubMed  CAS  Google Scholar 

  • Prass K, Ruscher K, Karsch M, Isaev N, Megow D, Priller J, Scharff A, Dirnagl U, Meisel A (2002) Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro. J Cereb Blood Flow Metab 22:520–525

    Article  PubMed  CAS  Google Scholar 

  • Prass K, Scharff A, Ruscher K, Lowl D, Muselmann C, Victorov I, Kapinya K, Dirnagl U, Meisel A (2003) Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34:1981–1986

    Article  PubMed  CAS  Google Scholar 

  • Ralph GS, Parham S, Lee SR, Beard GL, Craigon MH, Ward N, White JR, Barber RD, Rayner W, Kingsman SM, Mundy CR, Mazarakis ND, Krige D (2004) Identification of potential stroke targets by lentiviral vector mediated overexpression of HIF-1 alpha and HIF-2 alpha in a primary neuronal model of hypoxia. J Cereb Blood Flow Metab 24:245–258

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Ratan RR, Siddiq A, Aminova L, Lange PS, Langley B, Ayoub I, Gensert J, Chavez J (2004) Translation of ischemic preconditioning to the patient: prolyl hydroxylase inhibition and hypoxia inducible factor-1 as novel targets for stroke therapy. Stroke 35:2687–2689

    Article  PubMed  Google Scholar 

  • Rauca C, Zerbe R, Jantze H, Krug M (2000) The importance of free hydroxyl radicals to hypoxia preconditioning. Brain Res 868:147–149

    Article  PubMed  CAS  Google Scholar 

  • Rubaj A, Gustaw K, Zgodzinski W, Kleinrok Z, Sieklucka-Dziuba M (2000) The role of opioid receptors in hypoxic preconditioning against seizures in brain. Pharmacol Biochem Behav 67:65–70

    Article  PubMed  CAS  Google Scholar 

  • Ruscher K, Isaev N, Trendelenburg G, Weih M, Iurato L, Meisel A, Dirnagl U (1998) Induction of hypoxia inducible factor 1 by oxygen glucose deprivation is attenuated by hypoxic preconditioning in rat cultured neurons. Neurosci Lett 254:117–120

    Article  PubMed  CAS  Google Scholar 

  • Rybnikova E, Tulkova E, Pelto-Huikko M, Samoilov M (2002) Mild preconditioning hypoxia modifies nerve growth factor-induced gene A messenger RNA expression in the rat brain induced by severe hypoxia. Neurosci Lett 329:49–52

    Article  PubMed  CAS  Google Scholar 

  • Rybnikova E, Vataeva L, Tyulkova E, Gluschenko T, Otellin V, Pelto-Huikko M, Samoilov MO (2005) Mild hypoxia preconditioning prevents impairment of passive avoidance learning and suppression of brain NGFI-A expression induced by severe hypoxia. Behav Brain Res 160:107–114

    Article  PubMed  CAS  Google Scholar 

  • Rybnikova E, Sitnik N, Gluschenko T, Tjulkova E, Samoilov MO (2006) The preconditioning modified neuronal expression of apoptosis-related proteins of Bcl-2 superfamily following severe hypobaric hypoxia in rats. Brain Res 1089:195–202

    Article  PubMed  CAS  Google Scholar 

  • Rybnikova E, Gluschenko T, Tulkova E, Churilova A, Jaroshevich O, Baranova K, Samoilov M (2008) Preconditioning induces prolonged expression of transcription factors pCREB and NF-kappa B in the neocortex of rats before and following severe hypobaric hypoxia. J Neurochem 106:1450–1458

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Rybnikova E, Glushchenko T, Churilova A, Pivina S, Samoilov M (2011) Expression of glucocorticoid and mineralocorticoid receptors in hippocampus of rats exposed to various modes of hypobaric hypoxia: putative role in hypoxic preconditioning. Brain Res 1381:66–77

    Article  PubMed  CAS  Google Scholar 

  • Samoilov MO, Lazarevich EV, Semenov DG, Mokrushin AA, Tyul’kova EI, Romanovskii DY, Milyakova EA, Dudkin KN (2003) The adaptive effects of hypoxic preconditioning of brain neurons. Neurosci Behav Physiol 33:1–11

    Article  PubMed  CAS  Google Scholar 

  • Schipper HM (2004) Heme oxygenase expression in human central nervous system disorders. Free Radic Biol Med 37:1995–2011

    Article  PubMed  CAS  Google Scholar 

  • Schurr A, Reid KH, Tseng MT, West C, Rigor BM (1986) Adaptation of adult brain tissue to anoxia and hypoxia in vitro. Brain Res 374:244–248

    Article  PubMed  CAS  Google Scholar 

  • Semenov DG, Samoilov MO, Lazarewicz JW (2008) Preconditioning reduces hypoxia-evoked alterations in glutamatergic Ca2+ signaling in rat cortex. Acta Neurobiol Exp (Wars) 68:169–179

    Google Scholar 

  • Semenza GL (2007) Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405:1–9

    PubMed  CAS  Google Scholar 

  • Semenza GL (2009) Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 24:97–106

    Article  CAS  Google Scholar 

  • Seta KA, Spicer Z, Yuan Y, Lu G, Millhorn DE (2002) Responding to hypoxia: lessons from a model cell line. Sci STKE 2002:re11

    Article  PubMed  CAS  Google Scholar 

  • Shao G, Gong K-R, Li J, Xu X-J, Gao C-Y, Zeng X-Z, Lu G-W, Huo X (2009) Antihypoxic effects of neuroglobin in hypoxia-preconditioned mice and SH-SY5Y cells. Neurosignals 17:196–202

    Article  PubMed  CAS  Google Scholar 

  • Sharp FR, Bernaudin M (2004) HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 5:437–448

    Article  PubMed  CAS  Google Scholar 

  • Shu Y, Patel SM, Pac-Soo C, Fidalgo AR, Wan Y, Maze M, Ma D (2010) Xenon pretreatment attenuates anesthetic-induced apoptosis in the developing brain in comparison with nitrous oxide and hypoxia. Anesthesiology 113:360–368

    Article  PubMed  CAS  Google Scholar 

  • Siddiq A, Aminova LR, Troy CM, Suh K, Messer Z, Semenza GL, Ratan RR (2009) Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathways. J Neurosci 29:8828–8838

    Article  PubMed  CAS  Google Scholar 

  • Sommer C (2008) Ischemic preconditioning: postischemic structural changes in the brain. J Neuropathol Exp Neurol 67:85–92

    Article  PubMed  CAS  Google Scholar 

  • Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL (2003) Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res 63:6130–6134

    PubMed  CAS  Google Scholar 

  • Stapels M, Piper C, Yang T, Li M, Stowell C, Xiong Z-g, Saugstad J, Simon RP, Geromanos S, Langridge J, Lan J-q, Zhou A (2010) Polycomb group proteins as epigenetic mediators of neuroprotection in ischemic tolerance. Sci Signal 3:ra15

    Article  PubMed  CAS  Google Scholar 

  • Stenzel-Poore MP, Stevens SL, Xiong Z, Lessov NS, Harrington CA, Mori M, Meller R, Rosenzweig HL, Tobar E, Shaw TE, Chu X, Simon RP (2003) Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states. Lancet 362:1028–1037

    Article  PubMed  CAS  Google Scholar 

  • Stevens SL, Leung PY, Vartanian KB, Gopalan B, Yang T, Simon RP, Stenzel-Poore MP (2011) Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury. J Neurosci 31:8456–8463

    Article  PubMed  CAS  Google Scholar 

  • Stowe AM, Altay T, Freie AB, Gidday JM (2011) Repetitive hypoxia extends endogenous neurovascular protection for stroke. Ann Neurol 69:975–985

    Article  PubMed  CAS  Google Scholar 

  • Stowe AM, Wacker BK, Perfater JL, Freie AB, Gidday JM (2012) CCL2 upregulation triggers hypoxic preconditioning-induced protection from stroke. J Neuroinflammation 9:33

    Article  PubMed  CAS  Google Scholar 

  • Stroev SA, Gluschenko TS, Tjulkova EI, Spyrou G, Rybnikova EA, Samoilov MO, Pelto-Huikko M (2004a) Preconditioning enhances the expression of mitochondrial antioxidant thioredoxin-2 in the forebrain of rats exposed to severe hypobaric hypoxia. J Neurosci Res 78:563–569

    Article  PubMed  CAS  Google Scholar 

  • Stroev SA, Tjulkova EI, Gluschenko TS, Rybnikova EA, Samoilov MO, Pelto-Huikko M (2004b) The augmentation of brain thioredoxin-1 expression after severe hypobaric hypoxia by the preconditioning in rats. Neurosci Lett 370:224–229

    Article  PubMed  CAS  Google Scholar 

  • Stroev SA, Gluschenko TS, Tjulkova EI, Rybnikova EA, Samoilov MO, Pelto-Huikko M (2005) The effect of preconditioning on the Cu, Zn superoxide dismutase expression and enzyme activity in rat brain at the early period after severe hypobaric hypoxia. Neurosci Res 53:39–47

    Article  PubMed  CAS  Google Scholar 

  • Stroev SA, Tyul’kova EI, Glushchenko TS, Tugoi IA, Samoilov MO, Pelto-Huikko M (2009) Thioredoxin-1 expression levels in rat hippocampal neurons in moderate hypobaric hypoxia. Neurosci Behav Physiol 39:1–5

    Article  PubMed  CAS  Google Scholar 

  • Taie S, Ono J, Iwanaga Y, Tomita S, Asaga T, Chujo K, Ueki M (2009) Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning. J Clin Neurosci 16:1056–1060

    Article  PubMed  CAS  Google Scholar 

  • Takahashi R, Kobayashi C, Kondo Y, Nakatani Y, Kudo I, Kunimoto M, Imura N, Hara S (2004) Subcellular localization and regulation of hypoxia-inducible factor-2alpha in vascular endothelial cells. Biochem Biophys Res Commun 317:84–91

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Theus MH, Wei L, Cui L, Francis K, Hu X, Keogh C, Yu SP (2008) In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Exp Neurol 210:656–670

    Article  PubMed  CAS  Google Scholar 

  • Thiersch M, Lange C, Joly S, Heynen S, Le YZ, Samardzija M, Grimm C (2009) Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors. Eur J Neurosci 29:2291–2302

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Trachootham D, Lu W, Ogasawara MA, Nilsa R-DV, Huang P (2008) Redox regulation of cell survival. Antioxid Redox Signal 10:1343–1374

    Article  PubMed  CAS  Google Scholar 

  • Turovskaya MV, Turovsky EA, Zinchenko VP, Levin SG, Shamsutdinova AA, Godukhin OV (2011) Repeated brief episodes of hypoxia modulate the calcium responses of ionotropic glutamate receptors in hippocampal neurons. Neurosci Lett 496:11–14

    Article  PubMed  CAS  Google Scholar 

  • Tzeng YW, Lee LY, Chao PL, Lee HC, Wu RT, Lin AMY (2010) Role of autophagy in protection afforded by hypoxic preconditioning against MPP+ -induced neurotoxicity in SH-SY5Y cells. Free Radic Biol Med 49:839–846

    Article  PubMed  CAS  Google Scholar 

  • Valsecchi V, Pignataro G, Del Prete A, Sirabella R, Matrone C, Boscia F, Scorziello A, Sisalli MJ, Esposito E, Zambrano N, Di Renzo G, Annunziato L (2011) NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain preconditioning. Stroke 42:754–763

    Article  PubMed  CAS  Google Scholar 

  • van der Kooij MA, Groenendaal F, Kavelaars A, Heijnen CJ, van Bel F (2008) Neuroprotective properties and mechanisms of erythropoietin in in vitro and in vivo experimental models for hypoxia/ischemia. Brain Res Rev 59:22–33

    Article  PubMed  CAS  Google Scholar 

  • Vannucci RC, Towfighi J, Vannucci SJ (1998) Hypoxic preconditioning and hypoxic-ischemic brain damage in the immature rat: pathologic and metabolic correlates. J Neurochem 71:1215–1220

    Article  PubMed  CAS  Google Scholar 

  • Vellimana AK, Milner E, Azad TD, Harries MD, Zhou M-L, Gidday JM, Han BH, Zipfel GJ (2011) Endothelial nitric oxide synthase mediates endogenous protection against subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 42:776–782

    Article  PubMed  CAS  Google Scholar 

  • Wacker BK, Park TS, Gidday JM (2009) Hypoxic preconditioning-induced cerebral ischemic tolerance: role of microvascular sphingosine kinase 2. Stroke 40:3342–3348

    Article  PubMed  CAS  Google Scholar 

  • Wacker BK, Freie AB, Perfater JL, Gidday JM (2012) Junctional protein regulation by sphingosine kinase 2 contributes to blood-brain barrier protection in hypoxic preconditioning-induced cerebral ischemic tolerance. J Cereb Blood Flow Metab 32(6):1014–1023

    Google Scholar 

  • Wang X, Deng J, Boyle DW, Zhong J, Lee WH (2004) Potential role of IGF-I in hypoxia tolerance using a rat hypoxic-ischemic model: activation of hypoxia-inducible factor 1alpha. Pediatr Res 55:385–394

    Article  PubMed  CAS  Google Scholar 

  • Wang G, Zhou D, Wang C, Gao Y, Zhou Q, Qian G, DeCoster MA (2010) Hypoxic preconditioning suppresses group III secreted phospholipase A2-induced apoptosis via JAK2-STAT3 activation in cortical neurons. J Neurochem 114:1039–1048

    PubMed  CAS  Google Scholar 

  • Wei IH, Huang C-C, Tseng C-Y, Chang H-M, Tu H-C, Tsai M-H, Wen C-Y, Shieh J-Y (2008) Mild hypoxic preconditioning attenuates injury-induced NADPH-d/nNOS expression in brainstem motor neurons of adult rats. J Chem Neuroanat 35:123–132

    Article  PubMed  CAS  Google Scholar 

  • Wenger RH (2002) Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J 16:1151–1162

    Article  PubMed  CAS  Google Scholar 

  • Westberg JA, Serlachius M, Lankila P, Penkowa M, Hidalgo J, Andersson LC (2007) Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling. Stroke 38:1025–1030

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Wick A, Wick W, Waltenberger J, Weller M, Dichgans J, Schulz JB (2002) Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. J Neurosci 22:6401–6407

    PubMed  CAS  Google Scholar 

  • Wiesener MS, Jurgensen JS, Rosenberger C, Scholze CK, Horstrup JH, Warnecke C, Mandriota S, Bechmann I, Frei UA, Pugh CW, Ratcliffe PJ, Bachmann S, Maxwell PH, Eckardt KU (2003) Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs. FASEB J 17:271–273

    PubMed  CAS  Google Scholar 

  • Woitzik J, Hecht N, Schneider UC, Pena-Tapia PG, Vajkoczy P (2006) Increased vessel diameter of leptomeningeal anastomoses after hypoxic preconditioning. Brain Res 1115:209–212

    Article  PubMed  CAS  Google Scholar 

  • Wu L-Y, Ding A-S, Zhao T, Ma Z-M, Wang F-Z, Fan M (2004) Involvement of increased stability of mitochondrial membrane potential and overexpression of Bcl-2 in enhanced anoxic tolerance induced by hypoxic preconditioning in cultured hypothalamic neurons. Brain Res 999:149–154

    Article  PubMed  CAS  Google Scholar 

  • Wu LY, Ding AS, Zhao T, Ma ZM, Wang FZ, Fan M (2005) Underlying mechanism of hypoxic preconditioning decreasing apoptosis induced by anoxia in cultured hippocampal neurons. Neurosignals 14:109–116

    Article  PubMed  CAS  Google Scholar 

  • Wu L-Y, Ma Z-M, Fan X-L, Zhao T, Liu Z-H, Huang X, Li M-M, Xiong L, Zhang K, Zhu L-L, Fan M (2010a) The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells. Cell Stress Chaperones 15:387–394

    Article  PubMed  CAS  Google Scholar 

  • Wu W, Guo X, Jiang D, Sun J, Qiu Y, Zhu Y, Thakor NV, Tong S (2010b) Influence of hypoxic-preconditioning on autonomic regulation following global ischemic brain injury in rats. Neurosci Lett 480:191–195

    Article  PubMed  CAS  Google Scholar 

  • Xie J, Lu GW, Hou YZ (1999) Role of excitatory amino acids in hypoxic preconditioning. Biol Signals Recept 8:267–274

    Article  PubMed  CAS  Google Scholar 

  • Xu H, Lu A, Sharp FR (2011) Regional genome transcriptional response of adult mouse brain to hypoxia. BMC Genomics 12:499

    Article  PubMed  CAS  Google Scholar 

  • Yao S-y, Soutto M, Sriram S (2008) Preconditioning with cobalt chloride or desferrioxamine protects oligodendrocyte cell line (MO3.13) from tumor necrosis factor-alpha-mediated cell death. J Neurosci Res 86:2403–2413

    Article  PubMed  CAS  Google Scholar 

  • Yin W, Signore AP, Iwai M, Cao G, Gao Y, Johnnides MJ, Hickey RW, Chen J (2007) Preconditioning suppresses inflammation in neonatal hypoxic ischemia via Akt activation. Stroke 38:1017–1024

    Article  PubMed  CAS  Google Scholar 

  • Yu S, Zhao T, Guo M, Fang H, Ma J, Ding A, Wang F, Chan P, Fan M (2008) Hypoxic preconditioning up-regulates glucose transport activity and glucose transporter (GLUT1 and GLUT3) gene expression after acute anoxic exposure in the cultured rat hippocampal neurons and astrocytes. Brain Res 1211:22–29

    Article  PubMed  CAS  Google Scholar 

  • Zhan R-Z, Fujihara H, Baba H, Yamakura T, Shimoji K (2002) Ischemic preconditioning is capable of inducing mitochondrial tolerance in the rat brain. Anesthesiology 97:896–901

    Article  PubMed  CAS  Google Scholar 

  • Zhan L, Wang T, Li W, Xu ZC, Sun W, Xu E (2010) Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre-conditioning in adult rats. J Neurochem 114:897–908

    Article  PubMed  CAS  Google Scholar 

  • Zhan L, Peng W, Sun W, Xu E (2011) Hypoxic preconditioning induces neuroprotection against transient global ischemia in adult rats via preserving the activity of Na(+)/K(+)-ATPase. Neurochem Int 59:65–72

    Article  PubMed  CAS  Google Scholar 

  • Zhang WL, Lu GW (1999) Changes of adenosine and its A<sub>1</sub> receptor in hypoxic preconditioning. Biol Signals Recept 8:275–280

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Qian H, Zhao P, Hong SS, Xia Y (2006) Rapid hypoxia preconditioning protects cortical neurons from glutamate toxicity through delta-opioid receptor. Stroke 37:1094–1099

    Article  PubMed  CAS  Google Scholar 

  • Zhang N, Gao G, Bu X, Han S, Fang L, Li J (2007a) Neuron-specific phosphorylation of c-Jun N-terminal kinase increased in the brain of hypoxic preconditioned mice. Neurosci Lett 423:219–224

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Park TS, Gidday JM (2007b) Hypoxic preconditioning protects human brain endothelium from ischemic apoptosis by Akt-dependent survivin activation. Am J Physiol Heart Circ Physiol 292:H2573–H2581

    Article  PubMed  CAS  Google Scholar 

  • Zhang N, Yin Y, Han S, Jiang J, Yang W, Bu X, Li J (2011) Hypoxic preconditioning induced neuroprotection against cerebral ischemic injuries and its cPKCγ-mediated molecular mechanism. Neurochem Int 58:684–692

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Ohlemiller KK, McMahan BK, Gidday JM (2002) Mouse models of retinal ischemic tolerance. Invest Ophthalmol Vis Sci 43:1903–1911

    PubMed  Google Scholar 

  • Zhu Y, Ohlemiller KK, McMahan BK, Park TS, Gidday JM (2006) Constitutive nitric oxide synthase activity is required to trigger ischemic tolerance in mouse retina. Exp Eye Res 82:153–163

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Zhang Y, Ojwang BA, Brantley MA Jr, Gidday JM (2007) Long-term tolerance to retinal ischemia by repetitive hypoxic preconditioning: role of HIF-1alpha and heme oxygenase-1. Invest Ophthalmol Vis Sci 48:1735–1743

    Article  PubMed  Google Scholar 

  • Zhu Y, Zhang L, Gidday JM (2008) Deferroxamine preconditioning promotes long-lasting retinal ischemic tolerance. J Ocul Pharmacol Ther 24:527–535

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Robert D. Gilchrist & Jeffrey M. Gidday

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  1. Robert D. Gilchrist
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  2. Jeffrey M. Gidday
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Correspondence to Jeffrey M. Gidday .

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  1. , Departments of Neurosurgery, Washington University School of Medicine, South Kingshighway Boulevard, St. Louis, 63110, Missouri, USA

    Jeffrey M. Gidday

  2. , Department of Neurology, University of Miami Miller School of Med, Miami, 33136, Florida, USA

    Miguel A. Perez-Pinzon

  3. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Gilchrist, R.D., Gidday, J.M. (2013). Hypoxic Preconditioning in the CNS. In: Gidday, J., Perez-Pinzon, M., Zhang, J. (eds) Innate Tolerance in the CNS. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9695-4_8

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