Skip to main content
SpringerLink
Log in

Mechanisms of Anoxia Tolerance

A Novel Approach Using a Drosophila Model System

  • Chapter
Oxygen Transport to Tissue XX

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 454))

Abstract

The importance of hypoxia and tissue injury resulting from low O2 states can not be over-emphasized. This is a clinical situation that is frequently encountered and, although considerable new knowledge has been forthcoming from a number of laboratories over the past 2–3 decades, many important and clinically relevant questions are still unanswered. Furthermore, it has become clearer that hypoxia is not only a pathophysiologic event but can occur even during normal development, thus widening the potential biologic implications of the mechanisms that are important during O2 deprivation. Our laboratory has been interested in a number of these questions and, although we will not parade in this paper a considerable number of our previous observations, we highlight here some of the background which led to the studies detailed in this paper as well as our more recent studies on a model organism.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baird DH, Schalet AP and Wyman RJ. The passover locus in Drosophila melanogaster. Complex complementation and different effects on the Giant Fiber neural pathway. Genetics, 126: 1045–1059, 1990.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Banasiak KJ and Haddad GG. Hypoxia-induced Apoptosis: Effects of severity of hypoxia and role of p53 in neuronal cell death, submitted.

    Google Scholar 

  3. Ben Ari Y, Krnjevic K and Crepel V. Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons. Neuroscience, 37: 55–60, 1990.

    Article  CAS  PubMed  Google Scholar 

  4. Benveniste H, Drejer J, Schousboe A and Diemer NH. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neuwchem, 43: 1369–1374, 1984.

    Article  CAS  Google Scholar 

  5. Cherubine E, Ben-Ari Y and Krnjevic K. Anoxia produces smaller changes in synaptic transmission, membrane potential, and input resistance in immature rat hippocampus. J Neurophysiol, 62: 882–895, 1989.

    Google Scholar 

  6. Chih CP, Rosenthal M and Sick TJ. Ion leakage is reduced during anoxia in turtle brain: a potential survival strategy. Am J Physiol, 257(26): R1562–1564, 1989.

    Google Scholar 

  7. Chih CP, Feng ZC, Rosenthal M, Lutz PL and Sick TJ. Energy metabolism, ion homeostasis, and evoked potentials in anoxic turtle brain. Am J Physiol, 257(26): R854–R860, 1989.

    Google Scholar 

  8. Choi DW. Ionic dependence of glutamate neurotoxicity in cortical cell culture. J Neurosci, 7: 369–379, 1987

    CAS  PubMed  Google Scholar 

  9. Cummins TR, Donnelly DF, and Haddad GG. Effect of metabolic inhibition on the excitability of isolated hippocampal CA1 neurons: Developmental aspects. J Neurophysiol, 66: 1471–1482, 1991.

    CAS  PubMed  Google Scholar 

  10. Cummins TR, Jiang C, and Haddad GG. Human neocortical excitability is decreased during anoxia via sodium channel modulation. J Clin Invest, 91: 608–615, 1993.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Friedman JE and Haddad GG. Removal of extracellular sodium prevents anoxia-induced injury in rat CA1 hippocampal neurons. Brain Res, 641: 57–64, 1994.

    Article  CAS  PubMed  Google Scholar 

  12. Fung M-L and Haddad GG. Anoxic depolarization in CA.1 hippocampal neurons: Role of Na+-dependent mechanisms. Brain Res, in press.

    Google Scholar 

  13. Goldberg WJ. Kadingo RM and Barrett JN. Effects of ischemia-like conditions on cultured neurons: Protection by low Na+, low Ca2+ solutions. J Neurosci, 6: 3144–3151, 1986.

    CAS  PubMed  Google Scholar 

  14. Haddad GG and Donnelly DF. O2 Deprivation induces a major depolarization in brainstem neurons in the adult but not in the neonatal rat. J Physiol (London), 429: 411–428, 1990.

    CAS  Google Scholar 

  15. Haddad GG and Jiang C. O2 deprivation in the central nervous system: On mechanisms of neuronal response, differential sensitivity and injury. Prog Neurobiol, 40: 277–318, 1993.

    Article  CAS  PubMed  Google Scholar 

  16. Haddad GG, Sun Y-A, Wyman RJ and Xu T. Genetic basis of tolerance to O2 deprivation in Drosophila melanogaster, Proc Natl AcadSci, USA, in press.

    Google Scholar 

  17. Hansen AJ. Extracellular potassium concentration in juvenile and adult rat brain cortex during anoxia. Acta Physiol Scand, 99: 412–420, 1977.

    Article  CAS  PubMed  Google Scholar 

  18. Hansen AJ. Effect of anoxia on ion distribution in the brain. Physiol Rev, 65: 101–148, 1985.

    CAS  PubMed  Google Scholar 

  19. Hochachka PW. Defense strategies against hypoxia and hypothermia. Science, 231: 234–241, 1986.

    Article  CAS  PubMed  Google Scholar 

  20. Jiang C, Xia Y, and Haddad GG. Role of ATP sensitive K+ channels during anoxia: Major differences between rat (newborn, adult) and turtle neurons. J Physiol (London), 448: 599–612, 1992.

    CAS  Google Scholar 

  21. Jiang C and Haddad GG. Differential responses of neocortical neurons to glucose and/or O2 deprivation in the human and rat. J Neurophysiol, 68(6): 2165–2173, 1992.

    CAS  PubMed  Google Scholar 

  22. Jiang C and Haddad GG. Short periods of hypoxia activate a K+ current in central neurons. Brain Res, 64: 352–356, 1993.

    Article  Google Scholar 

  23. Jiang C and Haddad GG. A direct mechanism for sensing low oxygen levels by central neurons. Proc Natl Acad Sci, USA, 91: 7198–7201, 1994.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Jiang C, Sigworth FJ, and Haddad GG. O2 deprivation activates an ATP-inhibitable K+ channels in substantia nigra neurons. J Neurosci, 14: 5590–5602, 1994.

    CAS  PubMed  Google Scholar 

  25. Jiang C and Haddad GG. Oxygen deprivation inhibits a K+ channel independently of cytosolic factors in central neurons. J Physiol (London), 481, 1:15–26, 1994.

    CAS  Google Scholar 

  26. Jiang C and Haddad GG. Modulation of K+ channels by intracellular ATP in human neocortical neurons. J Neurophysiol, 77: 93–102, 1997.

    CAS  PubMed  Google Scholar 

  27. Krishnan SN, Sun Y-A, Mohsenin A, Wyman RJ and Haddad GG. Behavioral and electrophysiologic responses of Drosophila melanogaster to prolonged periods of anoxia. J Insect Physiol, 43(3): 203–210,1997

    Article  CAS  PubMed  Google Scholar 

  28. Kwei S, Jiang C, and Haddad GG. Acute anoxia-induced alterations in MAP2 immunoreactivity and neuronal morphology in rat hippocampus. Brain Res, 620: 203–210, 1993.

    Article  CAS  PubMed  Google Scholar 

  29. Maltepe E, Schmidt OV, Bannoch D, Bradfield CA and Simon MC. Abnormal angiogenesis and responses to glucose and O2 deprivation in mice lacking the protein ARNT. Nature 386: 403–407, 1997.

    Article  CAS  PubMed  Google Scholar 

  30. Marks JD, Friedman JE and Haddad GG. Vulnerability of CA1 neurons to glutamate is developmentally regulated. Dev Brain Res, in press.

    Google Scholar 

  31. O’Reilly JP, Jiang C, and Haddad GG. Major differences in response to graded hypoxia between hypoglossal and neocortical neurons, Brain Res, 683: 179–186, 1995.

    Article  PubMed  Google Scholar 

  32. O’Reilly JP and Haddad GG. Chronic hypoxia in vivo renders neocortical neurons more vulnerable to subsequent acute hypoxic stress. Brain Res, 711: 203–210, 1996.

    Article  PubMed  Google Scholar 

  33. O’Reilly J, Cummins TR and Haddad GG. Oxygen deprivation inhibits Na+ current in rat hippocampal neurones via protein Kinase C. J Physiol (London), in press.

    Google Scholar 

  34. Rothman SM. The neurotoxicity of excitatory amino acid is produced by passive chloride influx. J Neurosci, 5: 1483–1489, 1985.

    CAS  PubMed  Google Scholar 

  35. Sick TJ, Rosenthal M, LaManna JC and Lutz PL. Brain potassium ion homeostasis, anoxia, and metabolic inhibition in turtles and rats. Am J Physiol, 243(12): R281–288, 1982.

    CAS  PubMed  Google Scholar 

  36. Sick TJ, Lutz PL, LaManna JC and Rosenthal M. Comparative aspects of brain oxygen delivery and mitochondrial oxygen utilization in the turtle and rat. J Appl Physiol, 53: 1354–1359, 1982.

    CAS  PubMed  Google Scholar 

  37. Sick TJ, Chasnoff EP and Rosenthal M. Potassium ion homeostasis and mitochondrial redox status of turtle brain during and after ischemia. Am J Physiol, 248(17): R531–R540, 1985.

    CAS  PubMed  Google Scholar 

  38. Tanouye MA and Wyman RJ. Motor outputs of the giant nerve fiber in Drosophila. J Neurophysiol, 44: 405–421, 1980.

    CAS  PubMed  Google Scholar 

  39. Xia Y, Jiang C, and Haddad GG. Oxidative and glycolytic pathways in rat (newborn, adult) and turtle brain: Role during anoxia. Am J Physiol, 262: R595–603, 1992.

    CAS  PubMed  Google Scholar 

  40. Xia Y, Warshaw JB and Haddad GG. Chronic hypoxia causes opposite effects on glucose transporter 1 mRNA in mature versus immature rat brain. Brain Res, 675: 224–230, 1995.

    Article  CAS  PubMed  Google Scholar 

  41. Xia Y and Haddad GG. Voltage-sensitive Na+ channels increase in number in newborn rat brain after in utero hypoxia. Brain Res, 635: 339–344, 1994.

    Article  CAS  PubMed  Google Scholar 

  42. Xia Y, Warshaw JB and Haddad GG. Effect of chronic hypoxia on glucose transporters in heart and skeletal muscle of immature and adult rats. Am J Physiol, in press.

    Google Scholar 

  43. Xia Y and Haddad GG. Effect of prolonged O2 deprivation on Na+ channels: Differential regulation in adult versus fetal rat brain, submitted.

    Google Scholar 

  44. Young RS, During MJ, Donnelly DF, Aquila WJ, Perry VL, and Haddad GG. Effect of anoxia on excitatory amino acids in brain slices of rats and turtles: In vitro microdialysis study. Am J Physiol, 264(33): R716–719, 1993.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics and Cellular and Molecular Physiology Section of Respiratory Medicine, Yale University School of Medicine, 333 Cedar Street Fitkin Building, Room 506, New Haven, Connecticut, 06520, USA

    Gabriel G. Haddad

Authors
  1. Gabriel G. Haddad
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Antal G. Hudetz

  2. University of Maryland, Baltimore County, Baltimore, Maryland, USA

    Duane F. Bruley

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Haddad, G.G. (1998). Mechanisms of Anoxia Tolerance. In: Hudetz, A.G., Bruley, D.F. (eds) Oxygen Transport to Tissue XX. Advances in Experimental Medicine and Biology, vol 454. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4863-8_32

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4863-8_32

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7206-6

  • Online ISBN: 978-1-4615-4863-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation