Assessment of the Therapeutic Potential of Metallothionein-II Application in Focal Cerebral Ischemia In Vitro and In Vivo

2015 | journal article. A publication with affiliation to the University of Göttingen.

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​Assessment of the Therapeutic Potential of Metallothionein-II Application in Focal Cerebral Ischemia In Vitro and In Vivo​
Eidizadeh, A.; Khajehalichalehshtari, M.; Freyer, D. & Trendelenburg, G.​ (2015) 
PLoS ONE10(12) art. e0144035​.​ DOI: https://doi.org/10.1371/journal.pone.0144035 

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Authors
Eidizadeh, Abass; Khajehalichalehshtari, Manuel; Freyer, Dorette; Trendelenburg, George
Abstract
Metallothionein-II (MT-II) is an ubiquitously expressed small-molecular-weight protein and highly induced in various species and tissues upon stress, inflammation, and ischemia. MT-deficiency exacerbates ischemic injury in rodent stroke models in vitro and in vivo. However, there is conflicting data on the potential neuroprotective effect of exogenously applied metallothionein. Thus, we applied MT-II in an in vitro stroke model and intraperitoneally (i.p.) in two in vivo standard models of transient middle cerebral artery occlusion (MCAO) (a 'stringent' one [ 60min MCAO/48h reperfusion] and a 'mild' one [30min MCAO/72h reperfusion]), as well as i.v. together with recombinant tissue plasminogen activator (rtPA) to evaluate if exogenous MT-II-application protects against ischemic stroke. Whereas MT-II did not protect against 60min MCAO, there was a significant reduction of direct and indirect infarct volumes and neurological deficit in the MT-II (i.p.) treated animals in the 'mild' model at 3d after MCAO. Furthermore, MT-II also improved survival of the mice after MCAO, suppressed TNF-alpha mRNA induction in ischemic brain tissue, and protected primary neuronal cells against oxygen-glucose-deprivation in vitro. Thus, exogenous application of MT-II protects against ischemic injury in vitro and in vivo. However, long-term studies with different species and larger sampling sizes are required before a clinical use can be envisaged.
Issue Date
2015
Status
published
Publisher
Public Library Science
Journal
PLoS ONE 
ISSN
1932-6203
Sponsor
Open-Access Publikationsfonds 2015

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