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

doi:10.1007/s12640-009-9044-y

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

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28 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 language	English
Pages (from-to)	381-389
Number of pages	9
Journal	Neurotoxicity Research
Volume	15
Issue number	4
DOIs	https://doi.org/10.1007/s12640-009-9044-y
Publication status	Published - May 2009
Externally published	Yes

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title = "Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury",

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.",

author = "Chung, {R. S.} and Leung, {Y. K.} and Butler, {C. W.} and Y. Chen and Eaton, {E. D.} and Pankhurst, {M. W.} and West, {A. K.} and Guillemin, {G. J.}",

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T1 - Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury

AU - Chung, R. S.

AU - Leung, Y. K.

AU - Butler, C. W.

AU - Chen, Y.

AU - Eaton, E. D.

AU - Pankhurst, M. W.

AU - West, A. K.

AU - Guillemin, G. J.

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

Abstract

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