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Hypoxia pp 201-207 | Cite as

Astrocytes and Brain Hypoxia

  • Nephtali Marina
  • Vitaliy Kasymov
  • Gareth L. Ackland
  • Sergey Kasparov
  • Alexander V. GourineEmail author
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Adenosine Astrocytes ATP Breathing Glutamate Hypoxia Prostaglandins Vasodilation 

Notes

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.

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Feuerstein GZ, Wang X, Barone FC. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation. 1998;5:143–59.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gordon GR, Mulligan SJ, Macvicar BA. Astrocyte control of the cerebrovasculature. Glia. 2007;55:1214–21.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 21.
    Metea MR, Newman EA. Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J Neurosci. 2006;26:2862–70.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Mulligan SJ, Macvicar BA. Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature. 2004;431:195–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Nedergaard M, Ransom B, Goldman SA. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 2003;26:523–30.CrossRefPubMedGoogle Scholar
  24. 24.
    Paulson OB, Newman EA. Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science. 1987;237:896–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 26.
    Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci. 1995;108:2369–79.PubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 35.
    Zhang W, Stanimirovic D. Current and future therapeutic strategies to target inflammation in stroke. Curr Drug Targets Inflamm Allergy. 2002;1:151–66.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Nephtali Marina
    • 1
  • Vitaliy Kasymov
    • 1
  • Gareth L. Ackland
    • 2
  • Sergey Kasparov
    • 3
  • Alexander V. Gourine
    • 1
    Email author
  1. 1.Neuroscience, Physiology & PharmacologyUniversity College LondonLondonUK
  2. 2.Experimental Medicine, Wolfson Institute for Biomedical ResearchUniversity College LondonLondonUK
  3. 3.Department of Physiology and PharmacologyUniversity of BristolBristolUK

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