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01-05-2009

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

Authors: R. S. Chung, Y. K. Leung, C. W. Butler, Y. Chen, E. D. Eaton, M. W. Pankhurst, A. K. West, G. J. Guillemin

Published in: Neurotoxicity Research | Issue 4/2009

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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Title: Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury
Authors: R. S. Chung
Y. K. Leung
C. W. Butler
Y. Chen
E. D. Eaton
M. W. Pankhurst
A. K. West
G. J. Guillemin
Publication date: 01-05-2009
Publisher: Springer-Verlag
Published in: Neurotoxicity Research / Issue 4/2009
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-009-9044-y

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

Abstract

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Abstract

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