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Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury

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Abstract

The kynurenine pathway has been implicated as a major component of the neuroinflammatory response to brain injury and neurodegeneration. We found that the neurotoxic kynurenine pathway intermediate quinolinic acid (QUIN) is rapidly expressed, within 24 h, by reactive microglia following traumatic injury to the rodent neocortex. Furthermore, administration of the astrocytic protein metallothionein attenuated this neuroinflammatory response by reducing microglial activation (by approximately 30%) and QUIN expression. The suppressive effect of MT was confirmed upon cultured cortical microglia, with 1 μg/ml MT almost completely blocking interferon–gamma induced activation of microglia and QUIN expression. These results demonstrate the neuroimmunomodulatory properties of MT, which may have therapeutic applications for the treatment of traumatic brain injury.

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Acknowledgements

This work was supported by research grants from the Australian Research Council (DP0556630; LP0774820) and National Health and Medical Research Council (ID# 490025, 544913). RSC holds an Australian Research Council ARF Fellowship (DP0984673).

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Authors and Affiliations

  1. NeuroRepair Group, Menzies Research Institute, University of Tasmania, Private Bag 58, Hobart, TAS, 7001, Australia

    R. S. Chung, Y. K. Leung, C. W. Butler, E. D. Eaton, M. W. Pankhurst & A. K. West

  2. Centre for Immunology, University of New South Wales, Sydney, 2052, Australia

    Y. Chen & G. J. Guillemin

Authors
  1. R. S. Chung
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  2. Y. K. Leung
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  3. C. W. Butler
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  4. Y. Chen
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  5. E. D. Eaton
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  6. M. W. Pankhurst
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  7. A. K. West
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  8. G. J. Guillemin
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Correspondence to R. S. Chung or G. J. Guillemin.

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Chung, R.S., Leung, Y.K., Butler, C.W. et al. Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury. Neurotox Res 15, 381–389 (2009). https://doi.org/10.1007/s12640-009-9044-y

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  • DOI: https://doi.org/10.1007/s12640-009-9044-y

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