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Effect of Different Mild Hypoxia Manipulations on Kainic Acid-Induced Seizures in the Hippocampus of Rats

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Abstract

The protective effect of the mild hypoxia to the epilepsy has been widely tested. Although it is found that the hypoxia protects the brain by up-regulation of hypoxia-inducible factor-1α, few focused on systematic comparisons between different mild hypoxia manipulations and their effects. The male Sprague–Dawley rats were observed following exposure to hypoxia before and after epilepsy for 3 days with 90 min per day. The effects of different mild hypoxia manipulations on kainic acid-induced epilepsy were compared from the perspective of morphology, molecular biology and behavioral test. Results showed that different mild hypoxia manipulations could inhibit the cell apoptosis of kainic acid-induced rat hippocampus and improve their physiological functions. The effect of preconditioning group was better than that of postconditioning group and that of preconditioning and postconditioning with mild hypoxia group was the best among all the groups. The result showed that the preconditioning and postconditioning of mild hypoxia was recommended pre- and post-epilepsy and exposure to mild hypoxia should be prolonged. These findings might provide new ideas and methods for the clinical treatment of epilepsy.

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References

  1. Jobst BC, Siegel AM, Thadani VM et al (2000) Intraetable seizures of frontal lobe origin. Epilepsia 41:39–52

    Google Scholar 

  2. Kramer AF, Coyne JT, Strayer DL (1993) Cognitive function at high altitude. Hum Factors 35:329–344

    PubMed  CAS  Google Scholar 

  3. Shukitt-Hale B, Banderet LF, Lieberman HR (1998) Elevation-dependent symptom, mood and performance changes produced by exposure to hypobaric hypoxia. Int J Aviat Psychol 8:319–334

    Article  PubMed  CAS  Google Scholar 

  4. Sen Gupta J, Mathew L, Gopinath PM (1979) Effect of physical training at moderate altitude (1850 m) on hypoxic tolerance. Aviat Space Environ Med 50:714–716

    PubMed  CAS  Google Scholar 

  5. Robach P, Déchaux M, Jarrot S et al (2000) Operation Everest III: role of plasma volume expansion on VO (2) (max) during prolonged high-altitude exposure. J Appl Physiol 89:29–37

    PubMed  CAS  Google Scholar 

  6. Casas M, Casas H, Pagés T et al (2000) Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold. Aviat Space Environ Med 71:25–30

    Google Scholar 

  7. Wick A, Wick W, Waltenberger J et al (2002) Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. J Neurosci 22:1–7

    Google Scholar 

  8. Meerson FZ, Ustinova EE, Manukhina EB (1989) Prevention of cardiac arrhythmia by adaptation to hypoxia: regulatory mechanisms and cardiotropic effect. Biomed Biochim Acta 48:S83–S88

    PubMed  CAS  Google Scholar 

  9. Vovc E (1998) Arrhythmic effect of adaptation to intermittent hypoxia. Folia Med 40:51–54

    CAS  Google Scholar 

  10. Zhuang J, Zhou Z (1999) Protective effect of intermittent hypoxic adaptation on myocardium and its mechanisms. Biol Signals Recept 8:316–322

    Article  PubMed  CAS  Google Scholar 

  11. Chien CT, Chen CF, Hsu SM, Lee PH, Lai MK (1999) Protective mechanism of preconditioning hypoxia attenuates apoptosis formation during renal ischemia/reperfusion phase. Transplant Proc 31:12–13

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Emerson MR, Samson FE, Pazdernik TL (2000) Effect of hypoxia preconditioning on expression of metallothinein-1,2 and heme oxygenase-1 before and after kainic acid-induced seizures. Cell Mol Biol 46:19–26

    Google Scholar 

  14. Pohle W, Rauca C (1994) Hypoxia protects against the neurotoxicity of kainic acid. Brain Res 644:27–304

    Article  Google Scholar 

  15. Amano S, Obata T, Hazama F, Kashiro N, Shimada M (1990) Hypoxia prevents seizures and neuronal damages of the hippocampus induced by kainic acid in rats. Brain Res 523:121–126

    Article  PubMed  CAS  Google Scholar 

  16. Wang GL, Jiang BH, Rue EA, Semenza GL (1993) Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92:10–14

    Google Scholar 

  17. Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P (1996) Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271:29–37

    Google Scholar 

  18. Jiang BH, Semenza GL, Bauer C, Marti HH (1996) Hypoxiainducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol 271:72–80

    Google Scholar 

  19. 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 22:22–31

    Google Scholar 

  20. Bergeron M, Yu AY, Solway KE, Semenza GL, Sharp FR (1999) Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur J Neurosci 11:59–70

    Article  Google Scholar 

  21. 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 48:85–96

    Article  Google Scholar 

  22. Jones NM, Bergeron M (2001) Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat brain. J Cereb Blood Flow Metab 21:05–14

    Google Scholar 

  23. Halterman MW, Federoff HJ (1999) HIF-1alpha and p53 promote hypoxia-induced delayed neuronal death in models of CNS ischemia. Exp Neurol 159:65–72

    Article  PubMed  CAS  Google Scholar 

  24. Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M et al (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA 95:35–40

    Article  Google Scholar 

  25. Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C et al (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 97:26–31

    Article  Google Scholar 

  26. Prass K, Scharff A, Ruscher K, Löwl D, Muselmann C, Victorov I et al (2003) Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34:81–86

    Article  Google Scholar 

  27. Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76:105–116

    Article  PubMed  CAS  Google Scholar 

  28. Ruscher K, Freyer D, Karsch M, Isaev N, Megow D, Sawitzki B (2002) Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model. J Neurosci 22:291–301

    Google Scholar 

  29. Shetty AK, Turner DA (1999) Vulnerability of the dentate gyrus to aging and intracerebroventricular administration of kainic acid. Exp Neurol 158:491–503

    Article  PubMed  CAS  Google Scholar 

  30. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, London

    Google Scholar 

  31. Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294

    Article  PubMed  CAS  Google Scholar 

  32. Hirsch E, Baram TZ, Snead OC (1992) Ontogenic study of lithiumpilocarpine-induced status epilepticus in rats. Brain Res 583:120–126

    Article  PubMed  CAS  Google Scholar 

  33. Fujikawa DD, Shinmei SS, Cai B (2000) Kainic acid-induced seizures produce necrotic, not apoptotic neurons with internucleosomal DNA cleavage; implication for programmed cell death mechanisms. Neuroscience 98:42–53

    Article  Google Scholar 

  34. Henshall DC, Chen J, Simon RP (2000) Involvement of caspase-3like protease in the mechanism of cell death following focally evoked limbic seizures. J Neurochem 74:15–23

    Article  Google Scholar 

  35. Lan J, Henshall DC, Simon RP, Chen J (2000) Formation of the base modification 8-OH-2-deoxyguanosine and DNA fragmentation following seizures induced by systemic kainic acid in the rat. J Neurochem 74:302–309

    Article  PubMed  CAS  Google Scholar 

  36. Puig B, Ferrer I (2002) Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat. Neurosci Lett 321:182–186

    Article  PubMed  CAS  Google Scholar 

  37. Ientile R, Macaione V, Teletta M, Pedale S, Torre V, Macaione S (2001) Apoptosis and necrosis occurring in excitotoxic cells death ion isolated chick embryo retina. J Neurochem 79:71–78

    Article  PubMed  CAS  Google Scholar 

  38. Burda J, Danielisová V, Némethová M, Gottlieb M, Kravcuková P, Domoráková I, Mechírová E, Burda R (2009) Postconditioning and anticonditioning: possibilities to interfere to evoked apoptosis. Cell Mol Neurobiol 29:821–825

    Article  PubMed  Google Scholar 

  39. Yoo YM, Lee CJ, Lee U, Kim YJ (2006) Neuroprotection of adenoviral-vector-mediated GDNF expression against kainic-acid-induced excitotoxicity in the rat hippocampus. Experimental Neurol 2:407–417

    Article  Google Scholar 

  40. Domorákova I, Mechírova E, Dankova M, Danielisova V, Burda J (2009) Effect of antioxidant treatment in global ischemia and ischemic postconditioning in the rat hippocampus. Cell Mol Neurobiol 29:37–44

    Article  Google Scholar 

  41. Liu Y, Kato H, Nakata N, Kogure K (1993) Temporal profile of heat shock protein 70 synthesis in ischemic tolerance induced by preconditioning ischemia in rat hippocampus. Neuroscience 56:921–927

    Article  PubMed  CAS  Google Scholar 

  42. Andoh T, Lee SY, Chock B, Chiueh CC (2000) Preconditioning regulation of bcl-2 and p66shc by human NOS1 enhances tolerance to oxidative stress. FASEB 14:44–46

    Google Scholar 

  43. Zemke D, Smith JL, Reeves MJ, Majid A (2004) Ischemia and ischemic tolerance in the brain: an overview. Neurotoxicology 25:895–904

    Article  PubMed  CAS  Google Scholar 

  44. Blondeau N, Widmann C, Lazdunski M, Heurteaux C (2001) Activation of the nuclear factor-KB is a key event in brain tolerance. J Neurosci 21:68–77

    Google Scholar 

  45. Grabb MC, Choi DW (1999) Ischemic tolerance in murine cortical cell culture: critical role for NMDA receptors. J Neurosci 19:57–62

    Google Scholar 

  46. Gonzalez-Zulueta M, Feldmann AB, Klesse LJ, Kalb RG, Dillmann JF, Parada LF et al (2000) Requirement for nitric oxide activation of p21(ras)/extracellular regulated kinase in the neuronal ischemic preconditioning. Proc Natl Acad Sci USA 97:36–44

    Article  Google Scholar 

  47. Andoh T, Chiueh CC, Chock PB (2003) Cyclic GMP-dependent protein kinase regulates the expression of thioredoxin and thioredoxin peroxidase-1 during hormesis in response to oxidative stress-induced apoptosis. J Biol Chem 278:85–90

    Article  Google Scholar 

  48. Gulyaeva NV, Tkatchouk EN (1998) Antioxidant effects of interval hypoxia training in rat brain (Abstract). In: 12th European society of neurochemistry meeting, 31

  49. Gould E, Tanapat P (1997) Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult rat. Neuroscience 80:27–36

    Article  Google Scholar 

  50. Gray WP, May K, Sundstrom LE (2002) Seizure induced dentate neurogenesis does not diminish with age in rats. Neurosci Lett 330:35–38

    Article  Google Scholar 

  51. Harry GJ, Hellencourt CL (2003) Dentate gyrus: alteration that occur with hippocampal injury. Neurotoxicology 24:43–56

    Article  Google Scholar 

  52. Huang LE, Arany Z, Livingston DM, Bunn HF (1996) Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its a subunit. J Biol Chem 271:53–59

    Google Scholar 

  53. Huang LE, Gu J, Schau M, Bunn HF (1998) Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 95:87–92

    Article  Google Scholar 

  54. Kallio PJ, Wilson WJ, O’Brien S, Makino Y, Poellinger L (1999) Regulation of the hypoxia-inducible transcription factor 1α by the ubiquitin-proteasome pathway. J Biol Chem 274:19–25

    Article  Google Scholar 

  55. Salceda S, Caro J (1997) Hypoxia-inducible factor 1α (HIF-1α) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions: its stabilization by hypoxia depends upon redox-induced changes. J Biol Chem 272:42–47

    Article  Google Scholar 

  56. Grasso G, Sfacteria A, Meli F, Fodale V, Buemi M, Iacopino DG (2007) Neuroprotection by erythropoietin administration after experimental traumatic brain injury. Brain Res 28:99–105

    Article  Google Scholar 

  57. Verdonck O, Lahrech H, Francony G et al (2007) Erythropoietin protects from post-traumatic edema in the rat brain. J Cereb Blood Flow Metab 27:69–76

    Article  Google Scholar 

  58. Acharya MM, Hattiangady B, Shetty AK (2008) Progress in neuroprotective strategies for preventing epilepsy. Prog Neurobiol 84:363–404

    Article  PubMed  CAS  Google Scholar 

  59. Adams B, Sazgar M, Osehobo P, Van der Zee CE, Diamond J, Fahnestock M et al (1997) Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy. J Neurosci 17:88–96

    Google Scholar 

  60. Li S, Saragovi HU, Nedev H et al (2005) Differential actions of nerve growth factor receptors TrkA and p75NTR in a rat model of epileptogenesis. Mol Cell Neurosci 29:162–172

    Article  PubMed  CAS  Google Scholar 

  61. Binder DK, Croll SD, Gall CM, Scharfman HE (2001) BDNF and epilepsy: too much of a good thing? Trends Neurosci 24:47–53

    Article  PubMed  CAS  Google Scholar 

  62. Lähteinen S, Pitkänen A, Saarelainen T, Nissinen J, Koponen E, Castrén E (2002) Decreased BDNF signalling in transgenic mice reduces epileptogenesis. Eur J Neurosci 15:21–34

    Google Scholar 

  63. Unsain N, Nunez N, Anastasía A, Mascó DH (2008) Status epilepticus induces a TrkB to p75 neurotrophin receptor switch and increases brain-derived neurotrophic factor interaction with p75 neurotrophin receptor: an initial event in neuronal injury induction. Neuroscience 154:978–993

    Article  PubMed  CAS  Google Scholar 

  64. Kanter-Schlifke I, Georgievska B, Kirik D, Kokaia M (2007) Seizure suppression by GDNF gene therapy in animal models of epilepsy. Mol Ther 15:6–13

    Article  Google Scholar 

  65. Martin D, Miller G, Rosendahl M, Russell DA (1995) Potent inhibitory effects of glial derived neurotrophic factor against kainic acid mediated seizures in the rat. Brain Res 683:172–178

    Article  PubMed  CAS  Google Scholar 

  66. Croll SD, Goodman JH, Scharfman HE (2004) Vascular endothelial growth factor (VEGF) in seizures: a double-edged sword. Adv Exp Med Biol 548:57–68

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Yang Liu, Ju Zhong and Zhaohui Zheng for their contributions to this work.

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Authors and Affiliations

  1. Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 17 West Changle Road, Xi’an, 710032, China

    Yang Yang, Zhou Fei & Weiping Liu

  2. Department of Neurosurgery, The Zhumadian City Center Hospital, 747 Zhonghua Road, Zhumadian, 463000, China

    Yang Yang, Jianhua Chen & Li Li

  3. Department of Neurosurgery, The 159th Hospital of PLA, 1 Fengguang Road, Zhumadian, 463008, China

    Yusong Gao

  4. Department of Encephalopathy, Traditional Chinese Medicine Hospital of Shaan Xi Province, Xi’an, 710014, China

    Jun Chen

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  1. Yang Yang
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  2. Jianhua Chen
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  3. Li Li
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  4. Yusong Gao
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  5. Jun Chen
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  6. Zhou Fei
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Correspondence to Zhou Fei or Weiping Liu.

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Yang Yang, Jianhua Chen, Li Li, Yusong Gao and Jun Chen contributed equally to this work.

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Yang, Y., Chen, J., Li, L. et al. Effect of Different Mild Hypoxia Manipulations on Kainic Acid-Induced Seizures in the Hippocampus of Rats. Neurochem Res 38, 123–132 (2013). https://doi.org/10.1007/s11064-012-0899-6

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  • DOI: https://doi.org/10.1007/s11064-012-0899-6

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