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J Mol Neurosci. 2018 Oct;66(2):180-187. doi: 10.1007/s12031-018-1143-x. Epub 2018 Sep 3.

Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury.

Author information

1
Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel.
2
Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
3
Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel. danioffen@gmail.com.
4
Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. danioffen@gmail.com.

Abstract

Research into stroke is driven by frustration over the limited available therapeutics. Targeting a single aspect of this multifactorial disease contributes to the therapeutic boundaries. To overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding excitatory amino acid transporter 2 (EAAT2(, glutamate dehydrogenase 2 (GDH2), and nuclear factor E2-related factor 2 (Nrf2) genes, that acts synergistically to address the effected excito-oxidative axis. Here, we used the vasoconstrictor endothelin-1 (ET-1) to induce focal ischemic injury in mice by direct injection into the striatum. Mice treated with the mixture of these three genes show significant improvement in body balance, motor coordination, and decreased motor asymmetry compared to each gene separately. These results demonstrate that overexpression of the combined EAAT2, GDH2, and NRF2 genes can provide neuroprotection after ischemic injury.

KEYWORDS:

EAAT2 GDH2; Gene therapy; Ischemic injury; Nrf2; Stroke

PMID:
30178388
DOI:
10.1007/s12031-018-1143-x
[Indexed for MEDLINE]

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