Skip to main content

Advertisement

SpringerLink
Log in

Characterization of Gene Expression in the Rat Brainstem After Neonatal Hypoxic–Ischemic Injury and Antioxidant Treatment

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The perinatal brainstem is known to be very vulnerable to hypoxic–ischemic events which can lead to deafness, swallowing dysfunction, and defective respiratory control. The aim of the present work was to evaluate the potential neuroprotective effects of nicotine, melatonin, resveratrol, and docosahexaenoic acid on the expression of a panel of genes in the brainstem following hypoxic–ischemic damage. Quantitative PCR was used to examine gene expression 3 and 12 h after the damage, and immunohistochemistry was employed to evaluate neurons, astrocytes, and synaptic vesicles 24 h post insult. We found that the expression of some immediate-early genes, as well as that of inflammatory genes TNF-α, COX2, and caspase 3, was upregulated in response to the insult. Twenty-four hours after the damage, the percentage of NeuN and synaptophysin immunolabeled cells was found to be reduced while GFAP expression was upregulated. No differences were observed in ROS gene expression following treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Bellot B, Peyronnet-Roux J, Gire C, Simeoni U, Vinay L, Viemari JC (2014) Deficits of brainstem and spinal cord functions after neonatal hypoxia-ischemia in mice. Pediatr Res 75:723–730

    Article  CAS  PubMed  Google Scholar 

  2. de Vries LS, Jongmans MJ (2010) Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 95:F220–F224

    Article  PubMed  Google Scholar 

  3. Anderson P, Doyle LW, Victorian Infant Collaborative Study Group. (2003) Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. JAMA 289:3264–3272

    Article  PubMed  Google Scholar 

  4. Marlow N, Rose AS, Rands CE, Draper ES (2005) Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 90:F380–F387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Martinez-Biarge M, Diez-Sebastian J, Kapellou O, Gindner D, Allsop JM, Rutherford MA, Cowan FM (2011) Predicting motor outcome and death in term hypoxic-ischemic encephalopathy. Neurology 76:2055–2061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, Gustafson KE, Leach TM et al (2012) Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 366:2085–2092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Alonso-Alconada D, Alvarez A, Lacalle J, Hilario E (2012) Histological study of the protective effect of melatonin on neural cells after neonatal hypoxia-ischemia. Histol Histopathol 27:771–783

    CAS  PubMed  Google Scholar 

  8. Johnston MV (2001) Excitotoxicity in neonatal hypoxia. Ment Retard Dev Disabil Res Rev 7:229–234

    Article  CAS  PubMed  Google Scholar 

  9. Panigrahy A, White WF, Rava LA, Kinney HC (1995) Developmental changes in [3H]kainate binding in human brainstem sites vulnerable to perinatal hypoxia-ischemia. Neuroscience 67:441–454

    Article  CAS  PubMed  Google Scholar 

  10. Reinebrant HE, Wixey JA, Buller KM (2012) Disruption of raphé serotonergic neural projections to the cortex: a potential pathway contributing to remote loss of brainstem neurons following neonatal hypoxic-ischemic brain injury. Eur J Neurosci 36:3483–3491

    Article  PubMed  Google Scholar 

  11. Tang YP, Murata Y, Nagaya T, Noda Y, Seo H, Nabeshima T (1997) NGFI-B, c-fos, and c-jun mRNA expression in mouse brain after acute carbon monoxide intoxication. J Cereb Blood Flow Metab 17:771–780

    Article  CAS  PubMed  Google Scholar 

  12. Chen HH, Liu HM (1996) A new fluorescent histological marker for ischemic neurons, EA 50: correlated with Fos and Jun/AP-1 immunoreactivity. Histochem Cell Biol 105:375–382

    Article  CAS  PubMed  Google Scholar 

  13. Li GC, Li L, Liu RY, Rehman M, Lee WM (1992) Heat shock protein hsp70 protects cells from thermal stress even after deletion of its ATP-binding domain. Proc Natl Acad Sci U S A 89:2036–2040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim H, Huh PW, Kim C, Kim YJ, Park EM, Park YM (2001) Cerebral activation and distribution of inducible hsp110 and hsp70 mRNAs following focal ischemia in rat. Toxicology 167:135–144

    Article  CAS  PubMed  Google Scholar 

  15. Tyree MM, Dalgard C, O’Neill JT (2006) Impact of room air resuscitation on early growth response gene-1 in a neonatal piglet model of cerebral hypoxic ischemia. Pediatr Res 59:423–427

    Article  CAS  PubMed  Google Scholar 

  16. Zhang YM, Shi GG, Tang Z, Zheng JH, Li WQ, Guo FX, Jia QY (2006) Effects of N-n-butyl haloperidol iodide on myocardial ischemia/reperfusion injury and Egr-1 expression in rat. Acta Biochim Biophys Sin 38:435–441

    Article  CAS  PubMed  Google Scholar 

  17. Marti HJ, Bernaudin M, Bellail A, Schoch H, Euler M, Petit E, Risau W (2000) Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol 156:965–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Schalch P, Patejunas G, Retuerto M, Sarateanu S, Milbrandt J, Thakker G, Kim D, Carbray J et al (2004) Homozygous deletion of early growth response 1 gene and critical limb ischemia after vascular ligation in mice: evidence for a central role in vascular homeostasis. J Thorac Cardiovasc Surg 128:595–601

    Article  CAS  PubMed  Google Scholar 

  19. Kanngiesser M, Mair N, Lim HY, Zschiebsch K, Blees J, Haussler A, Brune B, Ferreiros N et al (2014) Hypoxia-inducible factor 1 regulates heat and cold pain sensitivity and persistence. Antioxid Redox Signal 20:2555–2571

    Article  CAS  PubMed  Google Scholar 

  20. Matsuda T, Abe T, Wu JL, Fujiki M, Kobayashi H (2005) Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral ischemia model. Neurol Res 27:503–508

    Article  CAS  PubMed  Google Scholar 

  21. Hilario E, Rey-Santano MC, Goni-de-Cerio F, Alvarez FJ, Gastiasoro E, Mielgo VE, Caballero A, Valls-i-Soler A et al (2005) Cerebral blood flow and morphological changes after hypoxic-ischaemic injury in preterm lambs. Acta Paediatr 94:903–911

    Article  PubMed  Google Scholar 

  22. Yang Q, Wu X, Sun J, Cui J, Li L (2014) Epigenetic features induced by ischemia-hypoxia in cultured rat astrocytes. Mol Neurobiol 53(1):436–445. doi:10.1007/s12035-014-9027-8

    Article  PubMed  Google Scholar 

  23. Pekny M, Wilhelmsson U, Pekna M (2014) The dual role of astrocyte activation and reactive gliosis. Neurosci Lett 565:30–38

    Article  CAS  PubMed  Google Scholar 

  24. Cojocaru IM, Cojocaru M, Tanasescu R, Iliescu I, Dumitrescu L, Silosi I (2009) Expression of IL-6 activity in patients with acute ischemic stroke. Rom J Intern Med 47:393–396

    CAS  PubMed  Google Scholar 

  25. Kalay S, Oztekin O, Tezel G, Aldemir H, Sahin E, Koksoy S, Akcakus M, Oygur N (2013) The effects of intraperitoneal pentoxifylline treatment in rat pups with hypoxic-ischemic encephalopathy. Pediatr Neurol 49:319–323

    Article  PubMed  Google Scholar 

  26. Li SJ, Liu W, Wang JL, Zhang Y, Zhao DJ, Wang TJ, Li YY (2014) The role of TNF-alpha, IL-6, IL-10, and GDNF in neuronal apoptosis in neonatal rat with hypoxic-ischemic encephalopathy. Eur Rev Med Pharmacol Sci 18:905–909

    PubMed  Google Scholar 

  27. Bradl M, Lassmann H (2010) Oligodendrocytes: biology and pathology. Acta Neuropathol 119:37–53

    Article  PubMed  Google Scholar 

  28. Ritter J, Schmitz T, Chew LJ, Buhrer C, Mobius W, Zonouzi M, Gallo V (2013) Neonatal hyperoxia exposure disrupts axon-oligodendrocyte integrity in the subcortical white matter. J Neurosci 33:8990–9002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schmitz T, Ritter J, Mueller S, Felderhoff-Mueser U, Chew LJ, Gallo V (2011) Cellular changes underlying hyperoxia-induced delay of white matter development. J Neurosci 31:4327–4344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Volpe JJ (2009) The encephalopathy of prematurity—brain injury and impaired brain development inextricably intertwined. Semin Pediatr Neurol 16:167–178

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tsai YW, Yang YR, Sun SH, Liang KC, Wang RY (2013) Post ischemia intermittent hypoxia induces hippocampal neurogenesis and synaptic alterations and alleviates long-term memory impairment. J Cereb Blood Flow Metab 33:764–773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guaiquil VH, Golde DW, Beckles DL, Mascareno EJ, Siddiqui MA (2004) Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts. Free Radic Biol Med 37:1419–1429

    Article  CAS  PubMed  Google Scholar 

  33. Li Q, Huang XJ, He W, Ding J, Jia JT, Fu G, Wang HX, Guo LJ (2009) Neuroprotective potential of fasudil mesylate in brain ischemia-reperfusion injury of rats. Cell Mol Neurobiol 29:169–180

    Article  CAS  PubMed  Google Scholar 

  34. McMahon S, Charbonneau M, Grandmont S, Richard DE, Dubois CM (2006) Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem 281:24171–24181

    Article  CAS  PubMed  Google Scholar 

  35. Alonso-Alconada D, Hilario E, Alvarez FJ, Alvarez A (2012) Apoptotic cell death correlates with ROS overproduction and early cytokine expression after hypoxia-ischemia in fetal lambs. Reprod Sci 19:754–763

    Article  CAS  PubMed  Google Scholar 

  36. Hejmadi MV, Dajas-Bailador F, Barns SM, Jones B, Wonnacott S (2003) Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes. Mol Cell Neurosci 24:779–786

    Article  CAS  PubMed  Google Scholar 

  37. Cilio MR, Ferriero DM (2010) Synergistic neuroprotective therapies with hypothermia. Semin Fetal Neonatal Med 15:293–298

    Article  PubMed  PubMed Central  Google Scholar 

  38. Huang SS, Tsai MC, Chih CL, Hung LM, Tsai SK (2001) Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia. Life Sci 69:1057–1065

    Article  CAS  PubMed  Google Scholar 

  39. Pan HC, Kao TK, Ou YC, Yang DY, Yen YJ, Wang CC, Chuang YH, Liao SL et al (2009) Protective effect of docosahexaenoic acid against brain injury in ischemic rats. J Nutr Biochem 20:715–725

    Article  CAS  PubMed  Google Scholar 

  40. Shimazawa M, Nakajima Y, Mashima Y, Hara H (2009) Docosahexaenoic acid (DHA) has neuroprotective effects against oxidative stress in retinal ganglion cells. Brain Res 1251:269–275

    Article  CAS  PubMed  Google Scholar 

  41. Revuelta M, Arteaga O, Montalvo H, Alvarez A, Hilario E, Martinez-Ibarguen A (2015) Antioxidant treatments recover the alteration of auditory-evoked potentials and reduce morphological damage in the inferior colliculus after perinatal asphyxia in rat. Brain Pathol. doi:10.1111/bpa.12272

    PubMed  Google Scholar 

  42. Rice JE III, Vannucci RC, Brierley JB (1981) The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9:131–141

    Article  PubMed  Google Scholar 

  43. Chen Y, Nie H, Tian L, Tong L, Yang L, Lao N, Dong H, Sang H et al (2013) Nicotine-induced neuroprotection against ischemic injury involves activation of endocannabinoid system in rats. Neurochem Res 38:364–370

    Article  CAS  PubMed  Google Scholar 

  44. Carloni S, Perrone S, Buonocore G, Longini M, Proietti F, Balduini W (2008) Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J Pineal Res 44:157–164

    Article  CAS  PubMed  Google Scholar 

  45. West T, Atzeva M, Holtzman DM (2007) Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury. Dev Neurosci 29:363–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Berman DR, Mozurkewich E, Liu Y, Barks J (2009) Docosahexaenoic acid pretreatment confers neuroprotection in a rat model of perinatal cerebral hypoxia-ischemia. Am J Obstet Gynecol 200:305.e1–305.e6

    Article  Google Scholar 

  47. Yang QK, Xiong JX, Yao ZX (2013) Neuron-NG2 cell synapses: novel functions for regulating NG2 cell proliferation and differentiation. Biomed Res Int 2013:402843

    PubMed  PubMed Central  Google Scholar 

  48. Orioli D, Colaluca IN, Stefanini M, Riva S, Dotti CG, Peverali FA (2006) Rac3-induced neuritogenesis requires binding to Neurabin I. Mol Biol Cell 17:2391–2400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Benitez SG, Castro AE, Patterson SI, Munoz EM, Seltzer AM (2014) Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat. PLoS One 9, e102056

    Article  PubMed  PubMed Central  Google Scholar 

  50. Tagliaferro P, Javier RA, Onaivi ES, Evrard SG, Lujilde J, Brusco A (2006) Neuronal cytoskeleton and synaptic densities are altered after a chronic treatment with the cannabinoid receptor agonist WIN 55,212-2. Brain Res 1085:163–176

    Article  CAS  PubMed  Google Scholar 

  51. Na JI, Na JY, Choi WY, Lee MC, Park MS, Choi KH, Lee JK, Kim KT et al (2015) The HIF-1 inhibitor YC-1 decreases reactive astrocyte formation in a rodent ischemia model. Am J Transl Res 7:751–760

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Alvarez-Diaz A, Hilario E, de Cerio FG, Valls-i-Soler A, Alvarez-Diaz FJ (2007) Hypoxic-ischemic injury in the immature brain—key vascular and cellular players. Neonatology 92:227–235

    Article  CAS  PubMed  Google Scholar 

  53. Donega V, Nijboer CH, van Tilborg G, Dijkhuizen RM, Kavelaars A, Heijnen CJ (2014) Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury. Exp Neurol 261:53–64

    Article  CAS  PubMed  Google Scholar 

  54. Xiong M, Yang Y, Chen GQ, Zhou WH (2009) Post-ischemic hypothermia for 24h in P7 rats rescues hippocampal neuron: association with decreased astrocyte activation and inflammatory cytokine expression. Brain Res Bull 79:351–357

    Article  CAS  PubMed  Google Scholar 

  55. Tuor UI, Hudzik TJ, Malisza K, Sydserff S, Kozlowski P, Del Bigio MR (2001) Long-term deficits following cerebral hypoxia-ischemia in four-week-old rats: correspondence between behavioral, histological, and magnetic resonance imaging assessments. Exp Neurol 167:272–281

    Article  CAS  PubMed  Google Scholar 

  56. Zins K, Pomyje J, Hofer E, Abraham D, Lucas T, Aharinejad S (2014) Egr-1 upregulates Siva-1 expression and induces cardiac fibroblast apoptosis. Int J Mol Sci 15:1538–1553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Okada M, Yan SF, Pinsky DJ (2002) Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation suppresses ischemic induction of Egr-1 and its inflammatory gene targets. FASEB J 16:1861–1868

    Article  CAS  PubMed  Google Scholar 

  58. Yan SF, Fujita T, Lu J, Okada K, Shan ZY, Mackman N, Pinsky DJ, Stern DM (2000) Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med 6:1355–1361

    Article  CAS  PubMed  Google Scholar 

  59. Wu H, Lei S, Yuan J, Liu X, Zhang D, Gu X, Zhang L, Xia Z (2013) Ischemic postconditioning downregulates Egr-1 expression and attenuates postischemic pulmonary inflammatory cytokine release and tissue injury in rats. J Surg Res 181:204–212

    Article  CAS  PubMed  Google Scholar 

  60. Wang HD, Fukuda T, Suzuki T, Hashimoto K, Liou SY, Momoi T, Kosaka T, Yamamoto K et al (1999) Differential effects of Bcl-2 overexpression on hippocampal CA1 neurons and dentate granule cells following hypoxic ischemia in adult mice. J Neurosci Res 57:1–12

    Article  CAS  PubMed  Google Scholar 

  61. Erickson JT, Millhorn DE (1994) Hypoxia and electrical stimulation of the carotid sinus nerve induce Fos-like immunoreactivity within catecholaminergic and serotoninergic neurons of the rat brainstem. J Comp Neurol 348:161–182

    Article  CAS  PubMed  Google Scholar 

  62. Goetzenich A, Hatam N, Preuss S, Moza A, Bleilevens C, Roehl AB, Autschbach R, Bernhagen J et al (2014) The role of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in late-phase preconditioning with xenon, isoflurane and levosimendan in rat cardiomyocytes. Interact Cardiovasc Thorac Surg 18:321–328

    Article  PubMed  Google Scholar 

  63. Pascual O, Ben AS, Rostaing P, Triller A, Bessis A (2012) Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc Natl Acad Sci U S A 109:E197–E205

    Article  CAS  PubMed  Google Scholar 

  64. Olivetto E, Simoni E, Guaran V, Astolfi L, Martini A (2015) Sensorineural hearing loss and ischemic injury: development of animal models to assess vascular and oxidative effects. Hear Res 327:58–68

    Article  CAS  PubMed  Google Scholar 

  65. Fujimoto M, Nakai A (2010) The heat shock factor family and adaptation to proteotoxic stress. FEBS J 277:4112–4125

    Article  CAS  PubMed  Google Scholar 

  66. Islam A, Abraham P, Hapner CD, Andrews-Shigaki B, Deuster P, Chen Y (2013) Heat exposure induces tissue stress in heat-intolerant, but not heat-tolerant, mice. Stress 16:244–253

    Article  CAS  PubMed  Google Scholar 

  67. Sun X, Crawford R, Liu C, Luo T, Hu B (2015) Development-dependent regulation of molecular chaperones after hypoxia-ischemia. Neurobiol Dis 82:123–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA (2003) VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 111:1843–1851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kovacs M, Akiskal HS, Gatsonis C, Parrone PL (1994) Childhood-onset dysthymic disorder. Clinical features and prospective naturalistic outcome. Arch Gen Psychiatry 51:365–374

    Article  CAS  PubMed  Google Scholar 

  70. Tarras SL, Diebel LN, Liberati DM, Ginnebaugh K (2013) Pharmacologic stimulation of the nicotinic anti-inflammatory pathway modulates gut and lung injury after hypoxia-reoxygenation injury. Surgery 154:841–847, discussion 847–8

    Article  PubMed  Google Scholar 

  71. Ma X, Jia Y, Zu S, Li R, Jia Y, Zhao Y, Xiao D, Dang N et al (2014) Alpha5 nicotinic acetylcholine receptor mediates nicotine-induced HIF-1alpha and VEGF expression in non-small cell lung cancer. Toxicol Appl Pharmacol 278:172–179

    Article  CAS  PubMed  Google Scholar 

  72. Acuna-Castroviejo D, Martin M, Macias M, Escames G, Leon J, Khaldy H, Reiter RJ (2001) Melatonin, mitochondria, and cellular bioenergetics. J Pineal Res 30:65–74

    Article  CAS  PubMed  Google Scholar 

  73. Hassell KJ, Ezzati M, Alonso-Alconada D, Hausenloy DJ, Robertson NJ (2015) New horizons for newborn brain protection: enhancing endogenous neuroprotection. Arch Dis Child Fetal Neonatal Ed 100(6):F541–F552. doi:10.1136/archdischild-2014-306284

    Article  PubMed  PubMed Central  Google Scholar 

  74. Rossler OG, Glatzel D, Thiel G (2015) Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors. Exp Cell Res 332:116–127

    Article  PubMed  Google Scholar 

  75. Yazir Y, Utkan T, Gacar N, Aricioglu F (2015) Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress. Physiol Behav 138:297–304

    Article  CAS  PubMed  Google Scholar 

  76. Simao F, Matte A, Pagnussat AS, Netto CA, Salbego CG (2012) Resveratrol preconditioning modulates inflammatory response in the rat hippocampus following global cerebral ischemia. Neurochem Int 61:659–665

    Article  CAS  PubMed  Google Scholar 

  77. Velten M, Britt RD Jr, Heyob KM, Tipple TE, Rogers LK (2014) Maternal dietary docosahexaenoic acid supplementation attenuates fetal growth restriction and enhances pulmonary function in a newborn mouse model of perinatal inflammation. J Nutr 144:258–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Basque Country Government (IT773/13).

Author information

Authors and Affiliations

  1. Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, E-48940, Vizcaya, Spain

    M. Revuelta, O. Arteaga, A. Alvarez & E. Hilario

  2. Department of Otorhinolaryngology, School of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, E-48940, Vizcaya, Spain

    A. Martinez-Ibargüen

Authors
  1. M. Revuelta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. Arteaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Martinez-Ibargüen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Hilario
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Revuelta.

Ethics declarations

All the experimental procedures received previous approval from the Animal Welfare Committee of the University of the Basque Country (UPV/EHU) and complied with the National Institutes of Health guidelines for the care and use of laboratory animals and the European Communities Directive 86/609/EEC regulating animal research.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Revuelta, M., Arteaga, O., Alvarez, A. et al. Characterization of Gene Expression in the Rat Brainstem After Neonatal Hypoxic–Ischemic Injury and Antioxidant Treatment. Mol Neurobiol 54, 1129–1143 (2017). https://doi.org/10.1007/s12035-016-9724-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-9724-6

Keywords

Search

Navigation