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Spinal Cord Molecular and Cellular Changes Induced by Adenoviral Vector- and Cell-Mediated Triple Gene Therapy after Severe Contusion

Overview of attention for article published in Frontiers in Pharmacology, November 2017
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Title
Spinal Cord Molecular and Cellular Changes Induced by Adenoviral Vector- and Cell-Mediated Triple Gene Therapy after Severe Contusion
Published in
Frontiers in Pharmacology, November 2017
DOI 10.3389/fphar.2017.00813
Pubmed ID
Authors

Andrei A. Izmailov, Tatyana V. Povysheva, Farid V. Bashirov, Mikhail E. Sokolov, Filip O. Fadeev, Ravil R. Garifulin, Boris S. Naroditsky, Denis Y. Logunov, Ilnur I. Salafutdinov, Yuri A. Chelyshev, Rustem R. Islamov, Igor A. Lavrov

Abstract

The gene therapy has been successful in treatment of spinal cord injury (SCI) in several animal models, although it still remains unavailable for clinical practice. Surprisingly, regardless the fact that multiple reports showed motor recovery with gene therapy, little is known about molecular and cellular changes in the post-traumatic spinal cord following viral vector- or cell-mediated gene therapy. In this study we evaluated the therapeutic efficacy and changes in spinal cord after treatment with the genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG), and neuronal cell adhesion molecule (NCAM) applied using both approaches. Therapeutic genes were used for viral vector- and cell-mediated gene therapy in two combinations: (1) VEGF+GDNF+NCAM and (2) VEGF+ANG+NCAM. For direct gene therapy adenoviral vectors based on serotype 5 (Ad5) were injected intrathecally and for cell-mediated gene delivery human umbilical cord blood mononuclear cells (UCB-MC) were simultaneously transduced with three Ad5 vectors and injected intrathecally 4 h after the SCI. The efficacy of both treatments was confirmed by improvement in behavioral (BBB) test. Molecular and cellular changes following post-traumatic recovery were evaluated with immunofluorescent staining using antibodies against the functional markers of motorneurons (Hsp27, synaptophysin, PSD95), astrocytes (GFAP, vimentin), oligodendrocytes (Olig2, NG2, Cx47) and microglial cells (Iba1). Our results suggest that both approaches with intrathecal delivery of therapeutic genes may support functional recovery of post-traumatic spinal cord via lowering the stress (down regulation of Hsp25) and enhancing the synaptic plasticity (up regulation of PSD95 and synaptophysin), supporting oligodendrocyte proliferation (up regulation of NG2) and myelination (up regulation of Olig2 and Cx47), modulating astrogliosis by reducing number of astrocytes (down regulation of GFAP and vimetin) and microglial cells (down regulation of Iba1).

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 13%
Student > Ph. D. Student 3 10%
Researcher 3 10%
Student > Postgraduate 3 10%
Student > Master 3 10%
Other 8 26%
Unknown 7 23%
Readers by discipline Count As %
Neuroscience 8 26%
Medicine and Dentistry 5 16%
Biochemistry, Genetics and Molecular Biology 3 10%
Agricultural and Biological Sciences 2 6%
Unspecified 1 3%
Other 2 6%
Unknown 10 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 November 2017.
All research outputs
#18,576,001
of 23,007,887 outputs
Outputs from Frontiers in Pharmacology
#8,364
of 16,313 outputs
Outputs of similar age
#249,699
of 325,998 outputs
Outputs of similar age from Frontiers in Pharmacology
#132
of 263 outputs
Altmetric has tracked 23,007,887 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,313 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 325,998 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 263 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.