Document Detail


Neuromyelitis optica pathology in rats following intraperitoneal injection of NMO-IgG and intracerebral needle injury.
MedLine Citation:
PMID:  24758159     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
INTRODUCTION: Animal models of neuromyelitis optica (NMO) are needed for drug testing and evaluation of NMO disease pathogenesis mechanisms.
RESULTS: We describe a novel passive-transfer model of NMO in which rats made seropositive for human anti-aquaporin-4 (AQP4) immunoglobulin G antibody (NMO-IgG) by intraperitoneal (IP) injections were subject to intracerebral needle injury. Following a single IP injection, NMO-IgG distributed rapidly to peripheral AQP4-expressing cells (kidney collecting duct, gastric glands, airways, skeletal muscle) and area postrema in brain, but not elsewhere in the central nervous system; however, no pathology was seen in brain, spinal cord, optic nerve or peripheral tissues. After testing various maneuvers to produce NMO-IgG-dependent pathology in brain, we found that transient puncture of brain parenchyma with a 28-gauge needle in NMO-IgG seropositive rats produced robust NMO pathology around the needle track, with loss of AQP4 and glial fibrillary acidic protein, granulocyte and macrophage infiltration, centrovascular deposition of activated complement, and blood-brain barrier disruption, with demyelination by 5 days. Pathology was not seen in rats receiving control (non-NMO) human IgG or in NMO-IgG-seropositive rats made complement-deficient by cobra venom factor. Interestingly, at 1 day a reversible, multifocal astrocytopathy was seen with loss of AQP4 and GFAP (but not myelin) in areas away from the needle track.
CONCLUSIONS: NMO-IgG-seropositivity alone is not sufficient to cause NMO pathology in rats, but a single intracerebral needle insertion, without pre-existing inflammation or infusion of pro-inflammatory factors, was sufficient to produce robust NMO pathology in seropositive rats.
Authors:
Nithi Asavapanumas; Alan S Verkman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-4-24
Journal Detail:
Title:  Acta neuropathologica communications     Volume:  2     ISSN:  2051-5960     ISO Abbreviation:  Acta Neuropathol Commun     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-4-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101610673     Medline TA:  Acta Neuropathol Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  48     Citation Subset:  -    
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