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Article

Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat

1
Department of Medical Biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
2
Institute of Fundamental Medicine and Biology, Kazan [Volga Region] Federal University, 420008 Kazan, Russia
3
Kazan Institute of Biochemistry and Biophysics, Federal Research Center of Kazan Scientific Center of Russian Academy of Sciences, 119991 Kazan, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6858; https://doi.org/10.3390/ijms21186858
Received: 26 August 2020 / Revised: 16 September 2020 / Accepted: 17 September 2020 / Published: 18 September 2020
(This article belongs to the Special Issue Neuroprotection: Rescue from Neuronal Death in the Brain)
Currently, the main fundamental and clinical interest for stroke therapy is focused on developing a neuroprotective treatment of a penumbra region within the therapeutic window. The development of treatments for ischemic stroke in at-risk patients is of particular interest. Preventive gene therapy may significantly reduce the negative consequences of ischemia-induced brain injury. In the present study, we suggest the approach of preventive gene therapy for stroke. Adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) or gene engineered umbilical cord blood mononuclear cells (UCB-MC) overexpressing recombinant VEGF, GDNF, and NCAM were intrathecally injected before distal occlusion of the middle cerebral artery in rats. Post-ischemic brain recovery was investigated 21 days after stroke modelling. Morphometric and immunofluorescent analysis revealed a reduction of infarction volume accompanied with a lower number of apoptotic cells and decreased expression of Hsp70 in the peri-infarct region in gene-treated animals. The lower immunopositive areas for astrocytes and microglial cells markers, higher number of oligodendrocytes and increased expression of synaptic proteins suggest the inhibition of astrogliosis, supporting the corresponding myelination and functional recovery of neurons in animals receiving preventive gene therapy. In this study, for the first time, we provide evidence of the beneficial effects of preventive triple gene therapy by an adenoviral- or UCB-MC-mediated intrathecal simultaneous delivery combination of vegf165, gdnf, and ncam1 on the preservation and recovery of the brain in rats with subsequent modelling of stroke. View Full-Text
Keywords: stroke; preventive gene therapy; adenoviral vector; VEGF; GDNF; NCAM; human umbilical cord blood mononuclear cells stroke; preventive gene therapy; adenoviral vector; VEGF; GDNF; NCAM; human umbilical cord blood mononuclear cells
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MDPI and ACS Style

Markosyan, V.; Safiullov, Z.; Izmailov, A.; Fadeev, F.; Sokolov, M.; Kuznetsov, M.; Trofimov, D.; Kim, E.; Kundakchyan, G.; Gibadullin, A.; Salafutdinov, I.; Nurullin, L.; Bashirov, F.; Islamov, R. Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat. Int. J. Mol. Sci. 2020, 21, 6858. https://doi.org/10.3390/ijms21186858

AMA Style

Markosyan V, Safiullov Z, Izmailov A, Fadeev F, Sokolov M, Kuznetsov M, Trofimov D, Kim E, Kundakchyan G, Gibadullin A, Salafutdinov I, Nurullin L, Bashirov F, Islamov R. Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat. International Journal of Molecular Sciences. 2020; 21(18):6858. https://doi.org/10.3390/ijms21186858

Chicago/Turabian Style

Markosyan, Vage, Zufar Safiullov, Andrei Izmailov, Filip Fadeev, Mikhail Sokolov, Maksim Kuznetsov, Dmitry Trofimov, Evgeny Kim, Grayr Kundakchyan, Airat Gibadullin, Ilnur Salafutdinov, Leniz Nurullin, Farid Bashirov, and Rustem Islamov. 2020. "Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat" International Journal of Molecular Sciences 21, no. 18: 6858. https://doi.org/10.3390/ijms21186858

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