Unique neuromyelitis optica pathology produced in naïve rats by intracerebral administration of NMO-IgG

Clicks: 87
ID: 114628
2013
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
Emerging

Ranked #394 of 438 articles by views in acta neuropathologica

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 438 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
Animal models of neuromyelitis optica (NMO) are needed for elucidation of disease mechanisms and for testing new therapeutics. Prior animal models of NMO involved administration of human anti-aquaporin-4 immunoglobulin G antibody (NMO-IgG) to rats with pre-existing neuroinflammation, or to naïve mice supplemented with human complement. We report here the development of NMO pathology following passive transfer of NMO-IgG to naïve rats. A single intracerebral infusion of NMO-IgG to adult Lewis rats produced robust lesions around the needle track in 100 % of rats; at 5 days there was marked loss of aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP) and myelin, granulocyte and macrophage infiltration, vasculocentric complement deposition, blood–brain barrier disruption, microglial activation and neuron death. Remarkably, a distinct ‘penumbra’ was seen around lesions, with loss of AQP4 but not of GFAP or myelin. No lesions or penumbra were seen in rats receiving control IgG. The size of the main lesion with loss of myelin was greatly reduced in rats made complement-deficient by cobra venom factor or administered NMO-IgG lacking complement-dependent cytotoxicity (CDC) effector function. However, the penumbra was seen under these conditions, suggesting a complement-independent pathogenesis mechanism. The penumbra was absent with NMO-IgG lacking both CDC and antibody-dependent cellular cytotoxicity (ADCC) effector functions. Finally, lesion size was significantly reduced after macrophage depletion with clodronate liposomes. These results: (i) establish a robust, passive-transfer model of NMO in rats that does not require pre-existing neuroinflammation or complement administration; (ii) implicate ADCC as responsible for a unique type of pathology also seen in human NMO; and (iii) support a pathogenic role of macrophages in NMO.
Reference Key
asavapanumas2013actaunique Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Nithi Asavapanumas;Julien Ratelade;A. S. Verkman;Nithi Asavapanumas;Julien Ratelade;A. S. Verkman;
Journal acta neuropathologica
Year 2013
DOI
doi:10.1007/s00401-013-1204-8
URL
https://link.springer.com/article/10.1007/s00401-013-1204-8
Keywords
pathology neurosciences

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.