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Metallothionein-IIA promotes initial neurite elongation and postinjury reactive neurite growth and facilitates healing after focal cortical brain injury


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Chung, RS, Vickers, JC, Chuah, MI and West, AK 2003 , 'Metallothionein-IIA promotes initial neurite elongation and postinjury reactive neurite growth and facilitates healing after focal cortical brain injury' , Journal of Neuroscience, vol. 23 , pp. 3336-3342 .

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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

Item Type: Article
Authors/Creators:Chung, RS and Vickers, JC and Chuah, MI and West, AK
Keywords: metallothionein; reactive sprouting; neurite sprouting; neurite growth; cortical brain injury; wound healing
Journal or Publication Title: Journal of Neuroscience
ISSN: 0270-6474
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