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Metallothionein-IIA Promotes Initial Neurite Elongation and Postinjury Reactive Neurite Growth and Facilitates Healing after Focal Cortical Brain Injury

Citation

Chung, RS and Vickers, JC and Chuah, MI and West, AK, Metallothionein-IIA Promotes Initial Neurite Elongation and Postinjury Reactive Neurite Growth and Facilitates Healing after Focal Cortical Brain Injury, Journal of Neuroscience, 23, (8) pp. 3336-3342. ISSN 0270-6474 (2003) [Refereed Article]

Abstract

Metallothioneins (MTs) are small, cysteine-rich, metal binding proteins. Their function has often been considered as stress-related proteins capable of protecting cells from heavy metal toxicity and oxidative free radicals. However, recent interest has focused on the brain-specific MT-III isoform, which has neurite-inhibitory properties. To investigate the effect of another MT isoform, human MT-IIA, on neurite growth, we used rat cortical neuron cultures. MT-IIA promoted a significant increase in the rate of initial neurite elongation of individually plated neurons. We also investigated the effect of MT-IIA on the neuronal response to axonal transection in vitro. MT-IIA promoted reactive axonal growth after injury, and, by 18 hr after transection, MT-IIA had promoted axonal growth across the injury tract. Exogenous application of MT-IIA after cortical brain injury promoted wound healing, as observed by a significant decrease in cellular degradation at 4 d after injury. Furthermore, MT-IIA-treated rats exhibited numerous SMI-312-immunoreactive axonal processes within the injury tract. This was in contrast to vehicle-treated animals, in which few axonal sprouts were observed. By 7 d after injury, MT-IIA treatment resulted in a total closing over of the injury tract by microglia, astrocytes, and reactive axonal processes. However, although some reactive axonal processes were observed within the injury tract of vehicle-treated rats, the tract itself was almost never entirely enclosed. These results are discussed in relation to a possible physiological role of metallothioneins in the brain, as well as in a therapeutic context.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Neurochemistry
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:Vickers, JC (Professor James Vickers)
Author:Chuah, MI (Dr Inn Chuah)
Author:West, AK (Professor Adrian West)
ID Code:28129
Year Published:2003
Web of Science® Times Cited:94
Deposited By:Anatomy and Physiology
Deposited On:2003-08-01
Last Modified:2007-10-17
Downloads:0

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