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Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS
Author(s) -
Rogers Scott D.,
Peters Christopher M.,
Pomonis James D.,
Hagiwara Hiromi,
Ghilardi Joseph R.,
Mantyh Patrick W.
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10173
Subject(s) - astrocyte , astrogliosis , glial fibrillary acidic protein , biology , gliosis , neuroglia , endocrinology , optic nerve , medicine , muscle hypertrophy , central nervous system , neuroscience , immunology , immunohistochemistry
The ability of mammalian central nervous system (CNS) neurons to survive and/or regenerate following injury is influenced by surrounding glial cells. To identify the factors that control glial cell function following CNS injury, we have focused on the endothelin B receptor (ET B R), which we show is expressed by the majority of astrocytes that are immunoreactive for glial acid fibrillary protein (GFAP) in both the normal and crushed rabbit optic nerve. Optic nerve crush induces a marked increase in ET B R and GFAP immunoreactivity (IR) without inducing a significant increase in the number of GFAP‐IR astrocytes, suggesting that the crush‐induced astrogliosis is due primarily to astrocyte hypertrophy. To define the role that endothelins play in driving this astrogliosis, artificial cerebrospinal fluid (CSF), ET‐1 (an ET A R and ET B R agonist), or Bosentan (a mixed ET A R and ET B R antagonist) were infused via osmotic minipumps into noninjured and crushed optic nerves for 14 days. Infusion of ET‐1 induced a hypertrophy of ET B R/GFAP‐IR astrocytes in the normal optic nerve, with no additional hypertrophy in the crushed nerve, whereas infusion of Bosentan induced a significant decrease in the hypertrophy of ET B R/GFAP‐IR astrocytes in the crushed but not in the normal optic nerve. These data suggest that pharmacological blockade of astrocyte ET B R receptors following CNS injury modulates glial scar formation and may provide a more permissive substrate for neuronal survival and regeneration. GLIA 41:180–190, 2003. © 2003 Wiley‐Liss, Inc.