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GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease

Overview of attention for article published in Neuroscience, September 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

Mentioned by

news
1 news outlet
twitter
1 tweeter

Citations

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48 Dimensions

Readers on

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76 Mendeley
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Title
GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease
Published in
Neuroscience, September 2015
DOI 10.1016/j.neuroscience.2015.07.014
Pubmed ID
Authors

D.B. Hoban, L. Howard, E. Dowd

Abstract

Constraints involving the delivery method of glial cell line-derived neurotrophic factor (GDNF) have hampered its efficacy as a neuroprotectant in Parkinson's disease. Ex vivo gene therapy, in which suitable cells, such as bone marrow-derived mesenchymal stem cells (MSCs), are genetically engineered to overexpress GDNF (GDNF-MSCs) prior to transplantation may be more beneficial than direct brain infusion of the neurotrophin. Previously, GDNF-MSCs have been assessed in the commonly employed 6-hydroxydopamine neurotoxic model of Parkinson's disease. In this study however, we used an emerging inflammatory model of Parkinson's disease (the lipopolysaccharide (LPS) model) to assess the ability of transplanted GDNF-MSCs to protect against LPS-induced neuroinflammation, neurodegeneration and behavioural impairment. 30 male Sprague Dawley rats were used in this experiment. Rats were performance matched based on baseline motor function tests into 3 groups (LPS lesion only, LPS lesion + GFP-MSCs, LPS lesion + GDNF-MSCs; n=10/group). Both cell groups received a unilateral intra-striatal transplant of either 200,000 GDNF-MSCs or 200,000 GFP-MSCs (as a control). One day post-transplantation, all rats received a unilateral intra-nigral infusion of LPS (10 μg in 2 μl sterile saline). Rats were sacrificed by transcardial perfusion-fixation and their brains were used for post mortem quantitative immunohistochemistry. Injection of LPS into the substantia nigra induced a pronounced local inflammatory response which resulted in 20% loss of nigrostriatal dopaminergic neurons and impaired contralateral motor function. Following transplantation of GDNF-MSCs to the striatum, dense areas of TH-positive staining directly proximal to the transplant site were observed. Most importantly, this effect was observed only in the GDNF-MSC transplanted group and not the GFP-MSC transplanted group demonstrating protection and/or sprouting of the dopaminergic terminals induced by the secreted GDNF. This study is the first to highlight the neurotrophic capability of GDNF in the inflammation-driven LPS model and, while future studies will endeavour to improve this approach by increasing cell survival, this work highlights the potential of GDNF delivery by ex vivo gene therapy using MSCs.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 76 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 1%
United States 1 1%
Russia 1 1%
Poland 1 1%
Unknown 72 95%

Demographic breakdown

Readers by professional status Count As %
Student > Master 14 18%
Student > Ph. D. Student 12 16%
Researcher 10 13%
Student > Bachelor 8 11%
Student > Doctoral Student 7 9%
Other 10 13%
Unknown 15 20%
Readers by discipline Count As %
Neuroscience 15 20%
Medicine and Dentistry 14 18%
Agricultural and Biological Sciences 11 14%
Biochemistry, Genetics and Molecular Biology 6 8%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Other 9 12%
Unknown 17 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 19 July 2015.
All research outputs
#1,389,042
of 12,290,236 outputs
Outputs from Neuroscience
#393
of 5,518 outputs
Outputs of similar age
#36,132
of 237,158 outputs
Outputs of similar age from Neuroscience
#20
of 162 outputs
Altmetric has tracked 12,290,236 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,518 research outputs from this source. They receive a mean Attention Score of 4.4. This one has done particularly well, scoring higher than 92% of its peers.
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 237,158 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 162 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.