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Astrocytes and Brain Hypoxia

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Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 903))

Abstract

Astrocytes provide the structural and functional interface between the cerebral circulation and neuronal networks. They enwrap all intracerebral arterioles and capillaries, control the flux of nutrients as well as the ionic and metabolic environment of the neuropil. Astrocytes have the ability to adjust cerebral blood flow to maintain constant PO2 and PCO2 of the brain parenchyma. Release of ATP in the brainstem, presumably by local astrocytes, helps to maintain breathing and counteract hypoxia-induced depression of the respiratory network. Astrocytes also appear to be involved in mediating hypoxia-evoked changes in blood–brain barrier permeability, brain inflammation, and neuroprotection against ischaemic injury. Thus, astrocytes appear to play a fundamental role in supporting neuronal function not only in normal conditions but also in pathophysiological states when supply of oxygen to the brain is compromised.

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References

  1. Alves PM, Fonseca LL, Peixoto CC, Almeida AC, Carrondo MJ, Santos H. NMR studies on energy metabolism of immobilized primary neurons and astrocytes during hypoxia, ischemia and hypoglycemia. NMR Biomed. 2000;13:438–48.

    Article  CAS  PubMed  Google Scholar 

  2. Blanco VM, Stern JE, Filosa JA. Tone-dependent vascular responses to astrocyte-derived signals. Am J Physiol Heart Circ Physiol. 2008;294:H2855–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bolton SJ, Anthony DC, Perry VH. Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood–brain barrier breakdown in vivo. Neuroscience. 1998;86:1245–57.

    Article  CAS  PubMed  Google Scholar 

  4. Bushong EA, Martone ME, Jones YZ, Ellisman MH. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci. 2002;22:183–92.

    CAS  PubMed  Google Scholar 

  5. Chavez JC, Baranova O, Lin J, Pichiule P. The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygen-dependent expression of erythropoietin in cortical astrocytes. J Neurosci. 2006;26:9471–81.

    Article  CAS  PubMed  Google Scholar 

  6. Collins PD, Connolly DT, Williams TJ. Characterization of the increase in vascular permeability induced by vascular permeability factor in vivo. Br J Pharmacol. 1993;109:195–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Feuerstein GZ, Wang X, Barone FC. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation. 1998;5:143–59.

    Article  CAS  PubMed  Google Scholar 

  8. Filosa JA, Bonev AD, Straub SV, Meredith AL, Wilkerson MK, Aldrich RW, Nelson MT. Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci. 2006;9:1397–403.

    Article  CAS  PubMed  Google Scholar 

  9. Fischer S, Wobben M, Marti HH, Renz D, Schaper W. Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc Res. 2002;63:70–80.

    Article  CAS  PubMed  Google Scholar 

  10. Gordon GR, Choi HB, Rungta RL, Ellis-Davies GC, Macvicar BA. Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature. 2008;456:745–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gordon GR, Mulligan SJ, Macvicar BA. Astrocyte control of the cerebrovasculature. Glia. 2007;55:1214–21.

    Article  PubMed  Google Scholar 

  12. Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S. Astrocytes control breathing through pH-dependent release of ATP. Science. 2010;329:571–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gourine AV, Llaudet E, Dale N, Spyer KM. Release of ATP in the ventral medulla during hypoxia in rats: role in hypoxic ventilatory response. J Neurosci. 2005;25:1211–8.

    Article  CAS  PubMed  Google Scholar 

  14. Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG. Synaptic islands defined by the territory of a single astrocyte. J Neurosci. 2007;27:6473–7.

    Article  CAS  PubMed  Google Scholar 

  15. Hayashi K, Nakao S, Nakaoke R, Nakagawa S, Kitagawa N, Niwa M. Effects of hypoxia on endothelial/pericytic co-culture model of the blood–brain barrier. Regul Pept. 2004;123:77–83.

    Article  CAS  PubMed  Google Scholar 

  16. Heurteaux C, Lauritzen I, Widmann C, Lazdunski M. Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci U S A. 1995;92:4666–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M. Connexin 43 hemichannels are permeable to ATP. J Neurosci. 2008;28:4702–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Knot HJ, Zimmermann PA, Nelson MT. Extracellular K(+)-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K(+) channels. J Physiol. 1996;492:419–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mark KS, Davis TP. Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol. 2002;282:H1485–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Masuda S, Okano M, Yamagishi K, Nagao M, Ueda M, Sasaki R. A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes. J Biol Chem. 1994;269:19488–93.

    CAS  PubMed  Google Scholar 

  21. Metea MR, Newman EA. Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J Neurosci. 2006;26:2862–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mulligan SJ, Macvicar BA. Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature. 2004;431:195–9.

    Article  CAS  PubMed  Google Scholar 

  23. Nedergaard M, Ransom B, Goldman SA. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 2003;26:523–30.

    Article  CAS  PubMed  Google Scholar 

  24. Paulson OB, Newman EA. Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science. 1987;237:896–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Prass K, Scharff A, Ruscher K, Lowl D, Muselmann C, Victorov I, Kapinya K, Dirnagl U, Meisel A. Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke. 2003;34:1981–6.

    Article  CAS  PubMed  Google Scholar 

  26. Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci. 1995;108:2369–79.

    CAS  PubMed  Google Scholar 

  27. Sakurai-Yamashita Y, Shigematsu K, Yamashita K, Niwa M. Expression of MCP-1 in the hippocampus of SHRSP with ischemia-related delayed neuronal death. Cell Mol Neurobiol. 2006;26:823–31.

    Article  CAS  PubMed  Google Scholar 

  28. Semenza GL, Agani F, Booth G, Forsythe J, Iyer N, Jiang BH, Leung S, Roe R, Wiener C, Yu A. Structural and functional analysis of hypoxia-inducible factor 1. Kidney Int. 1997;51:553–5.

    Article  CAS  PubMed  Google Scholar 

  29. Serebryakov V, Zakharenko S, Snetkov V, Takeda K. Effects of prostaglandins E1 and E2 on cultured smooth muscle cells and strips of rat aorta. Prostaglandins. 1994;47:353–65.

    Article  CAS  PubMed  Google Scholar 

  30. Silver IA, Deas J, Erecinska M. Ion homeostasis in brain cells: differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience. 1997;78:589–601.

    Article  CAS  PubMed  Google Scholar 

  31. Stanimirovic D, Zhang W, Howlett C, Lemieux P, Smith C. Inflammatory gene transcription in human astrocytes exposed to hypoxia: roles of the nuclear factor-kappaB and autocrine stimulation. J Neuroimmunol. 2001;119:365–76.

    Article  CAS  PubMed  Google Scholar 

  32. Takata F, Dohgu S, Nishioku T, Takahashi H, Harada E, Makino I, Nakashima M, Yamauchi A, Kataoka Y. Adrenomedullin-induced relaxation of rat brain pericytes is related to the reduced phosphorylation of myosin light chain through the cAMP/PKA signaling pathway. Neurosci Lett. 2009;449:71–5.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang W, Smith C, Howlett C, Stanimirovic D. Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in vitro is mediated by IL-1beta. J Cereb Blood Flow Metab. 2000;20:967–78.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang W, Smith C, Shapiro A, Monette R, Hutchison J, Stanimirovic D. Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. J Neuroimmunol. 1999;101:148–60.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang W, Stanimirovic D. Current and future therapeutic strategies to target inflammation in stroke. Curr Drug Targets Inflamm Allergy. 2002;1:151–66.

    Article  CAS  PubMed  Google Scholar 

  36. Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci. 2003;6:43–50.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The research in our laboratories referred to in this report was funded by The Wellcome Trust and British Heart Foundation. A.V.G. is a Wellcome Trust Senior Research Fellow (ref. 079040); G.L.A. is an Academy of Medical Sciences/Health Foundation Clinician Scientist.

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Authors and Affiliations

  1. Neuroscience, Physiology & Pharmacology, University College London, London, UK

    Nephtali Marina, Vitaliy Kasymov & Alexander V. Gourine

  2. Experimental Medicine, Wolfson Institute for Biomedical Research, University College London, London, UK

    Gareth L. Ackland

  3. Department of Physiology and Pharmacology, University of Bristol, Bristol, UK

    Sergey Kasparov

Authors
  1. Nephtali Marina
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  2. Vitaliy Kasymov
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  3. Gareth L. Ackland
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  4. Sergey Kasparov
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  5. Alexander V. Gourine
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Corresponding author

Correspondence to Alexander V. Gourine .

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Editors and Affiliations

  1. Altitude Research Center, University of Colorado Anschutz Medical, AURORA, Colorado, USA

    Robert C. Roach

  2. Institute for Altitude Medicine, Telluride, Colorado, USA

    Peter H. Hackett

  3. Division of Physiology 0623A, University of California - San Diego, La Jolla, California, USA

    Peter D. Wagner

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Marina, N., Kasymov, V., Ackland, G.L., Kasparov, S., Gourine, A.V. (2016). Astrocytes and Brain Hypoxia. In: Roach, R., Hackett, P., Wagner, P. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 903. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7678-9_14

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