Get access

Role of gap junctional coupling in astrocytic networks in the determination of global ischaemia-induced oxidative stress and hippocampal damage

Authors

  • Jose L. Perez Velazquez,

    1. Brain and Behaviour Programme and Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    2. Department of Paediatrics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Larisa Kokarovtseva,

    1. Brain and Behaviour Programme and Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Raheleh Sarbaziha,

    1. Brain and Behaviour Programme and Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Zina Jeyapalan,

    1. Brain and Behaviour Programme and Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Yevgen Leshchenko

    1. Brain and Behaviour Programme and Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author

Dr J. L. Perez Velazquez, The Hospital for Sick Children, Department of Neurology, room 6535 Hill Wing, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
E-mail: jose-luis.perez-velazquez@sickkids.ca

Abstract

While there is evidence that gap junctions play important roles in the determination of cell injuries, there is not much known about mechanisms by which gap junctional communication may exert these functions. Using a global model of transient ischaemia in rats, we found that pretreatment with the gap junctional blockers carbenoxolone, 18α-glycyrrhetinic acid and endothelin, applied via cannulae implanted into the hippocampus in one hemisphere, resulted in decreased numbers of TUNEL-positive neurons, as compared with the contralateral hippocampus that received saline injection. Post-treatment with carbenoxolone for up to 30 min after the stroke injury still resulted in decreased cell death, but post-treatment at 90 min after the ischaemic insult did not result in differences in cell death. However, quinine, an inhibitor of Cx36-mediated gap junctional coupling, did not result in appreciable neuroprotection. Searching for a possible mechanism for the observed protective effects, possible actions of the gap junctional blockers in the electrical activity of the hippocampus during the ischaemic insult were assessed using intracerebral recordings, with no differences observed between the saline-injected and the contralateral drug-injected hippocampus. However, a significant reduction in lipid peroxides, a measure of free radical formation, in the hippocampus treated with carbenoxolone, revealed that the actions of gap junctional coupling during injuries may be causally related to oxidative stress. These observations suggest that coupling in glial networks may be functionally important in determining neuronal vulnerability to oxidative injuries.

Ancillary