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

Citation

Chung, RS and Leung, YK and Butler, CW and Chen, Y and Eaton, ED and Pankhurst, MW and West, AK and Guillemin, GJ, Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury , Neurotoxicity Research: An International Journal on Processes and Mechanisms in Neurodegeneration, Apoptosis, Neuroprotection and Regeneration, 15, (4) pp. 381-389. ISSN 1029-8428 (2009) [Refereed Article]

DOI: doi:10.1007/s12640-009-9044-y

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 lg/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.

Item Details

Item Type:Refereed Article
Keywords:Traumatic brain injury; Neuroinflammation; Neuron-glia interactions
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Chung, RS (Associate Professor Roger Chung)
Author:Leung, YK (Dr Jacqueline Leung)
Author:Butler, CW (Mr Christopher Butler)
Author:Eaton, ED (Dr Emma Eaton)
Author:Pankhurst, MW (Mr Michael Pankhurst)
Author:West, AK (Professor Adrian West)
ID Code:60051
Year Published:2009
Web of Science® Times Cited:15
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-01-07
Last Modified:2010-04-15
Downloads:0

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