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

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)381-389
Number of pages9
JournalNeurotoxicity Research
Volume15
Issue number4
DOIs
Publication statusPublished - May 2009
Externally publishedYes

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