The GFAP Monoclonal Antibody GA-5 Identifies Astrocyte Remodeling and Glio-Vascular Uncoupling During the Evolution of EAE.
Cell Mol Neurobiol
; 42(5): 1615-1622, 2022 Jul.
Article
en En
| MEDLINE
| ID: mdl-33544272
ABSTRACT
To examine how astrocyte activation is regulated at different phases of relapsing-remitting EAE, we performed an immunofluorescent analysis of the spinal cord using the anti-glial fibrillary acidic protein (GFAP) monoclonal antibody GA-5. In keeping with previous studies, gray matter astrocytes showed strongly increased GFAP expression during the peak phase of disease (14 days post-immunization), which remained elevated during the remission phase (21-28 days post-immunization). In sharp contrast, during the peak phase of disease, the GA-5 signal in sub-meningeal white matter transiently disappeared in areas containing high levels of infiltrating leukocytes, but during the remission phase, the GFAP signal was fully restored. Parallel staining of the same sections with a polyclonal GFAP antibody confirmed elevated GFAP expression in the gray matter but no loss of signal in white matter. Interestingly, loss of GA-5 signal in sub-meningeal white matter was strongly associated with vascular disruption as defined by extravascular fibrinogen leak and by glio-vascular uncoupling, as defined by dissociation of AQP4-positive astrocyte endfeet and CD31-positive blood vessels. GA-5-negative areas were also associated with demyelination. These findings demonstrate a novel staining pattern of a GFAP antibody during EAE progression and suggest that the GFAP epitope recognized by the GA-5 monoclonal antibody transiently disappears as white matter astrocytes undergo remodeling during the peak phase of EAE. They also suggest that the GA-5 antibody provides a novel tool to identify astrocyte remodeling in other neurological conditions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encefalomielitis Autoinmune Experimental
/
Sustancia Blanca
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Mol Neurobiol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos