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• W2098113460 abstract "HomeStrokeVol. 39, No. 11Neuroglobin: Endogenous Neuroprotectant or Maintenance of Homeostasis? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBNeuroglobin: Endogenous Neuroprotectant or Maintenance of Homeostasis? Jesper Kelsen Christian Ansgar Hundahl and Anders Hay-Schmidt Jesper KelsenJesper Kelsen Department of Neurosurgery, University Hospital of Copenhagen (Rigshospitalet), Copenhagen, Denmark Search for more papers by this author Christian Ansgar HundahlChristian Ansgar Hundahl Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark Search for more papers by this author and Anders Hay-SchmidtAnders Hay-Schmidt Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark Search for more papers by this author Originally published18 Sep 2008https://doi.org/10.1161/STROKEAHA.108.526533Stroke. 2008;39:e177–e178Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 18, 2008: Previous Version 1 To the Editor:We would like to comment on the latest experimental stroke study in a neuroglobin (Ngb) knock-in mouse by Wang et al1 The intriguing idea that Ngb could act as a reservoir of oxygen, facilitate oxygen transportation or act as a scavenger of reactive oxygen species in the brain has been the main research hypotheses since its discovery.2 Notably, the investigation of the role of Ngb in pathophysiological conditions like hypoxia and ischemia has promoted the idea of an endogenous neuroprotectant.3 However, we would like to challenge the ruling theory of a possible neuroprotective function of Ngb. Instead, we propose a homeostatic role based on the distinct expression pattern (Figure),4 the old evolutionary history and highly conserved structure of Ngb.5Download figureDownload PowerPointFigure. Ngb expression is restricted to a few neuron populations in the evolutionary oldest parts of the brain. This suggests Ngb involvement in the sleep-wake cycle, circadian rhythm or food regulation. A, Ngb in situ hybridization (Ngb ISH) staining and (B) Ngb immunohistochemistry (Ngb IHC) of a coronal section in a C57:black mouse at bregma level 2.00. Bed nuclei of the stria terminalis (BST), lateral septal nucleus (LS), medial preoptic area (MPA).Wang et al1 thoroughly characterized the differences in infarct volume, malondialdehyde (MDA) formation and sensorimotor function in Ngb-overexpressing transgenic (Ngb-Tg) mice and wild-type littermates. Forced Ngb expression significantly reduced the cortical infarct volumes 22 hours after 2-hour intraluminal transient middle cerebral artery occlusion whereas no difference was seen in the subcortical structures at that time point. Surprisingly, subcortical structures were significantly spared in Ngb-Tg 14 days after 60-minute focal transient ischemia. Unfortunately, this phenomenon is not discussed by the authors. The less MDA formation after 8 and 22 hours in Ngb-Tg is interpreted as a possible antioxidative action of Ngb. We think MDA production reflects the significant difference in stroke volumes after 22 hours. MDA is not only a surrogate biomarker of reactive oxygen species but probably also of infarct size.Previously published differences in Ngb expression are attributable to the use of different antibodies and ribonucleotide probes. In our hands the cortical and striatal Ngb expression was always very scarce despite ischemic challenge.6 Mice even expressed less Ngb in the mentioned areas compared to rats. In addition we only found colocalization of Ngb and nNOS in very few neuronal populations residing outside the cortex and striatum.7 In our opinion Ngb does not have a pathophysiological action as oxygen buffer or sensor. We do not dispute that Ngb can act as an endogenous neuroprotectant in the brain, but we do dispute the notion that Ngb primarily offers protection against ischemia in cortical and subcortical areas. Finally, the possible mechanism of neuroprotective action remains to be elucidated and has not been further characterized by Wang et al.1Sources of FundingC.A.H. is supported by The Danish Medical Research Council, NOVO Nordisk Foundation and The Lundbeck Foundation.DisclosuresNone.1 Wang X, Liu J, Zhu H, Tejima E, Tsuji K, Murata Y, Atochin DN, Huang PL, Zhang C, Lo EH. Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia. Stroke. 2008; 39: 1869–1874.LinkGoogle Scholar2 Burmester T, Weich B, Reinhardt S, Hankeln T. A vertebrate globin expressed in the brain. Nature. 2000; 407: 520–523.CrossrefMedlineGoogle Scholar3 Greenberg DA, Jin K, Khan AA. Neuroglobin: an endogenous neuroprotectant. Curr Opin Pharmacol. 2008; 8: 20–24.CrossrefMedlineGoogle Scholar4 Hundahl CA, Allen GC, Nyengaard JR, Dewilde S, Carter BD, Kelsen J, Hay-Schmidt A. Neuroglobin in the rat brain: localization. Neuroendocrinology. 2008; epub May 2. DOI: 10.1159/000129698.Google Scholar5 Hankeln T, Ebner B, Fuchs C, Gerlach F, Haberkamp M, Laufs TL, Roesner A, Schmidt M, Weich B, Wystub S, Saaler-Reinhardt S, Reuss S, Bolognesi M, De Sanctis D, Marden MC, Kiger L, Moens L, Dewilde S, Nevo E, Avivi A, Weber RE, Fago A, Burmester T. Neuroglobin and cytoglobin in search of their role in the vertebrate globin family. J Inorg Biochem. 2005; 99: 110–119.CrossrefMedlineGoogle Scholar6 Hundahl C, Kelsen J, Kjaer K, Ronn LC, Weber RE, Geuens E, Hay-Schmidt A, Nyengaard JR. Does neuroglobin protect neurons from ischemic insult? A quantitative investigation of neuroglobin expression following transient MCAo in spontaneously hypertensive rats. Brain Res. 2006; 1085: 19–27.CrossrefMedlineGoogle Scholar7 Hundahl CA, Kelsen J, Dewilde S, Hay-Schmidt A. Neuroglobin in the rat brain (II): co-localization with neurotransmitters. Neuroendocrinology. 2008; epub May 29. DOI: 10.1159/000135617.Google Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Gøtzsche C, Woldbye D, Hundahl C and Hay‐Schmidt A (2022) Neuroglobin deficiency increases seizure susceptibility but does not affect basal behavior in mice, Journal of Neuroscience Research, 10.1002/jnr.25105, 100:10, (1921-1932), Online publication date: 1-Oct-2022. De Simone G, Sbardella D, Oddone F, Pesce A, Coletta M and Ascenzi P (2021) Structural and (Pseudo-)Enzymatic Properties of Neuroglobin: Its Possible Role in Neuroprotection, Cells, 10.3390/cells10123366, 10:12, (3366) Fiocchetti M, Cracco P, Montalesi E, Solar Fernandez V, Stuart J and Marino M (2021) Neuroglobin and mitochondria: The impact on neurodegenerative diseases, Archives of Biochemistry and Biophysics, 10.1016/j.abb.2021.108823, 701, (108823), Online publication date: 1-Apr-2021. Ascenzi P, di Masi A, Leboffe L, Fiocchetti M, Nuzzo M, Brunori M and Marino M (2016) Neuroglobin: From structure to function in health and disease, Molecular Aspects of Medicine, 10.1016/j.mam.2016.10.004, 52, (1-48), Online publication date: 1-Dec-2016. Fabrizius A, Andre D, Laufs T, Bicker A, Reuss S, Porto E, Burmester T and Hankeln T (2016) Critical re-evaluation of neuroglobin expression reveals conserved patterns among mammals, Neuroscience, 10.1016/j.neuroscience.2016.07.042, 337, (339-354), Online publication date: 1-Nov-2016. Burmester T and Hankeln T (2014) Function and evolution of vertebrate globins, Acta Physiologica, 10.1111/apha.12312, 211:3, (501-514), Online publication date: 1-Jul-2014. ZHANG B, JI X, ZHANG S, REN H, WANG M, GUO C and LI Y (2013)(2013) Hemin-mediated neuroglobin induction exerts neuroprotection following ischemic brain injury through PI3K/Akt signaling, Molecular Medicine Reports, 10.3892/mmr.2013.1523, 8:2, (681-685), Online publication date: 1-Aug-2013. Haines B, Mao X, Xie L, Spusta S, Zeng X, Jin K and Greenberg D (2013) Neuroglobin expression in neurogenesis, Neuroscience Letters, 10.1016/j.neulet.2013.04.039, 549, (3-6), Online publication date: 1-Aug-2013. Hundahl C, Kelsen J and Hay-Schmidt A (2012) Neuroglobin and Cytoglobin expression in the human brain, Brain Structure and Function, 10.1007/s00429-012-0480-8, 218:2, (603-609), Online publication date: 1-Mar-2013. Li S, Li W, Zhang M, Wu Y and Hu Y (2012) The Role of Neuroglobin in the Neuroprotection of Limb Ischemic Preconditioning in Rats, Molecular Neurobiology, 10.1007/s12035-012-8373-7, 47:1, (197-208), Online publication date: 1-Feb-2013. Zara S, De Colli M, Rapino M, Pacella S, Nasuti C, Sozio P, Di Stefano A and Cataldi A (2013) Ibuprofen and Lipoic Acid Conjugate Neuroprotective Activity Is Mediated by Ngb/Akt Intracellular Signaling Pathway in Alzheimer's Disease Rat Model, Gerontology, 10.1159/000346445, 59:3, (250-260), . Brittain T (2012) The Anti-Apoptotic Role of Neuroglobin, Cells, 10.3390/cells1041133, 1:4, (1133-1155) Shang A, Liu K, Wang H, Wang J, Hang X, Yang Y, Wang Z, Zhang C and Zhou D (2011) Neuroprotective effects of neuroglobin after mechanical injury, Neurological Sciences, 10.1007/s10072-011-0772-4, 33:3, (551-558), Online publication date: 1-Jun-2012. Chen L, Xiong Y, Kong F, Qu M, Wang Q, Chen X, Wang J and Zhu L (2011) Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling, Journal of Neurochemistry, 10.1111/j.1471-4159.2011.07275.x, 120:1, (157-164), Online publication date: 1-Jan-2012. November 2008Vol 39, Issue 11 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.108.526533PMID: 18802204 Originally publishedSeptember 18, 2008 PDF download Advertisement" @default.
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