Role of the Permeability Transition in Glutamate-Mediated Neuronal Injury

  • Ian J. Reynolds
  • Teresa G. Hastings


Glutamate can injure neurons in a way that is likely relevant to a number of acute neurodegenerative states, including stroke and head trauma. It is also likely that glutamate contributes to neurons degeneration in chronic diseases as well. Many studies have established a relationship between the bioenergetic state of neurons and their vulnerability to injury, and more-recent investigations have placed mitochondria at the center of the event cascade linking glutamate receptor activation to neuronal death. The key question posed at the start of this review concerned the role of the PTP in this process, however, and this is much less clear. There are significant concerns in interpretating studies which suggest that transition occurs in intact neurons, because of the difficulty in attributing alterations in membrane potential to pore activation, so these studies remain suggestive but not conclusive. Morphological approaches also imply pore involvement but contain similar methodological concerns. It is evident that CsA is neuroprotective under certain circumstances, but there are multiple mechanisms by which this might be so, and FK506 sometimes has neuroprotective actions as well. No other drugs that alter membrane potential have shown neuroprotective effects. Thus, the body of evidence linking the PTP to excitotoxicity, though suggestive and intriguing, remains to be firmly established.


Mitochondrial Membrane Potential Neuronal Injury Mitochondrial Permeability Transition Mitochondrial Permeability Transition Pore Cerebellar Granule Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Ian J. Reynolds
    • 1
  • Teresa G. Hastings
    • 2
  1. 1.Department of PharmacologyUniversity of PittsburghPittsburgh
  2. 2.Department of Neurology and NeuroscienceUniversity of PittsburghPittsburgh

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