intracisternal delivery of nfkappab-inducible scaav2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

Clicks: 254
ID: 195456
2014
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Popular

Ranked #128 of 189 articles by views in international journal of nanomedicine

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 189 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions respectively known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions.We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e. cortex, hippocampus and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally-designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approx. 5-fold. Neurons, astrocytes and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid.Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation.These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are required to enhance
Reference Key
ebockstael2014frontiersintracisternal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Olivier eBockstael;Liliane eTenenbaum;Deniz eDalkara;Catherine eMelas;Olivier eDe Witte;Marc eLevivier;Abdelwahed eChtarto
Journal international journal of nanomedicine
Year 2014
DOI
10.3389/fnmol.2014.00092
URL
http://journal.frontiersin.org/Journal/10.3389/fnmol.2014.00092/full
Keywords
neuroinflammation aav cerebrospinal fluid neuropsychiatry biological psychiatry

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.