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Cerebral ischemic tolerance induced by 3-nitropropionic acid is associated with increased expression of erythropoietin in rats

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Summary

To examine the changes in erythropoietin (Epo) protein and its mRNA expression in rat brain subjected to focal ischemia and possible mechanism of the preconditioning of mitochondrial toxin 3-nitropropionic acid (3-NPA), rats were administrated either vehicle or 3-NPA at a dose of 20 mg/kg, intraperitoneally (ip), 3 days prior to a 2-h middle cerebral artery occlusion followed by 24-h reperfusion. Infarct volumes were measured by using 2, 3, 5 triphenylte trazolinm chloride (TTC) staining, and Epo protein and its mRNA levels were assessed by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Our results showed that after reperfusion, Epo was found to be expressed extensively in the rat brain. It was most apparent in the basal nuclei and hippocampus, and was, to some extent, present in cortex. Preconditioning with 3-NPA caused a reduction in infarct volume. The expression of both Epo protein and mRNA increased significantly in the different brain areas in the 3-NPA pretreated group as compared with the non-pretreated ischemia model group. These results suggested that preconditioning with low dose 3-NPA could induce ischemic tolerance and neuro-protective effects by increasing the Epo expression in the ischemic and ischemia-related areas.

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References

  1. Abe H, Nowak T S Jr et al. Gene expression and induced ischemic tolerance following brief insults. Acta Neurobiol Exp (Wars), 1996,56:3–8

    CAS  Google Scholar 

  2. Kuroiwa T, Yamada I, Endo S et al. 3-nitropropionic acid preconditioning ameliorates delayed neurological deterioration and infarction after transient focal cerebral ischemia in gerbils. Neurosci Lett, 2000,283:145–148

    Article  PubMed  CAS  Google Scholar 

  3. Nakase H, Heimann A, Uranishi R et al. Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial inhibitor. Neurosci Lett, 2000, 290:105–108

    Article  PubMed  CAS  Google Scholar 

  4. Sugino T, Nozaki K, Takagi Y et al. 3-Nitropropionic acid induces ischemic tolerance in gerbil hippocampus in vivo. Neurosci Lett, 1999,259:9–12

    Article  PubMed  CAS  Google Scholar 

  5. Marti H H, Bernaudin M, Petit E et al. Neuroprotection and angiogenesis: dual role of erythropoietin in brain ischemia. Physiol Sci, 2000,15:225–229

    CAS  Google Scholar 

  6. Bernaudin M, Marti H H, Roussel S et al. A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab, 1999,19:643–651

    Article  PubMed  CAS  Google Scholar 

  7. Brines M L, Ghezzi P, Keenan S et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA, 2000,97: 10526–10531

    Article  PubMed  CAS  Google Scholar 

  8. Sakanaka M, Wen T C, Matsuda S et al. In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA, 1998,95:4635–4640

    Article  PubMed  CAS  Google Scholar 

  9. Prass K, Scharff A, Ruscher K et al. Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke, 2003,34:1981–1986

    Article  PubMed  CAS  Google Scholar 

  10. Ruscher K, Freyer D, Karsch M et al. Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model. J Neurosci, 2002,22:10291–10301

    PubMed  CAS  Google Scholar 

  11. Longa E Z, Weinstein P R, Carlson S et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 1989,20:84–91

    PubMed  CAS  Google Scholar 

  12. Swanson R A, Morton M T, Tsao-Wu G et al. A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab, 1990,10:290–293

    PubMed  CAS  Google Scholar 

  13. Brambrink A M, Schneider A, Noga H et al. Tolerance-inducing dose of 3-nitropropi-onic acid modulates bcl-2 and Bax balance in the rat brain: a potential mechanism of chemical preconditioning. J Cereb Blood Flow Metab, 2000,20:1425–1436

    Article  PubMed  CAS  Google Scholar 

  14. Yao H, Takasawa R, Fukudu K et al. (2001) DNA fragmentation in ischemic core and penumbra in focal cerebral ischemia in rats. Mol Brain Res, 2001,91:112–118

    Article  PubMed  CAS  Google Scholar 

  15. Horiguchi T, Kis B, Rajapakse N et al. (2003): Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats. Stroke, 2001,34:1015–1020

    Article  CAS  Google Scholar 

  16. Ehrenreich H, Hasselblatt M, Dembowski C et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med, 2002,8:495–505

    PubMed  CAS  Google Scholar 

  17. Wiessner C, Allegrini P R, Ekatodramis D et al. Increased cerebral infarct volumes in polyglobulic mice overexpressing erythropoietin. J Cereb Blood Flow Metab, 2001, 21:857–864

    Article  PubMed  CAS  Google Scholar 

  18. Dawson T M et al. Preconditioning-mediated neuroprotection through erythropoietin? Lancet, 2002, 359:96–97

    Article  PubMed  Google Scholar 

  19. von Amim C A, Timmler M, Ludolph A C et al. Adenosine receptor up-regulation: initiated upon preconditioning but not upheld. Neuroreport, 2000,11:1223–1226

    Article  Google Scholar 

  20. Yao Z, Tong J, Tan X et al. Role of reactive oxygen species in acetylcholine-induced preconditioning in cardiomyocytes. Am J Physiol, 1999,277: H2504–H2509

    PubMed  CAS  Google Scholar 

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ZHU Hongcan, male, born in 1966, M.D., Ph.D.

This project was supported by scientific research Funds of Zhengzhou Municipal Government, China (No. 04BA60AB YD08).

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Zhu, H., Sun, S., Li, H. et al. Cerebral ischemic tolerance induced by 3-nitropropionic acid is associated with increased expression of erythropoietin in rats. J. Huazhong Univ. Sc. Technol. 26, 440–443 (2006). https://doi.org/10.1007/s11596-006-0416-8

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  • DOI: https://doi.org/10.1007/s11596-006-0416-8

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