Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS

Scott D. Rogers, Christopher M. Peters, James D. Pomonis, Hiromi Hagiwara, Joseph R. Ghilardi, Patrick W. Mantyh

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

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 (ETBR), 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 ETBR 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 ETAR and ETBR agonist), or Bosentan (a mixed ETAR and ETBR antagonist) were infused via osmotic minipumps into noninjured and crushed optic nerves for 14 days. Infusion of ET-1 induced a hypertrophy of ETBR/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 ETBR/GFAP-IR astrocytes in the crushed but not in the normal optic nerve. These data suggest that pharmacological blockade of astrocyte ETBR receptors following CNS injury modulates glial scar formation and may provide a more permissive substrate for neuronal survival and regeneration.

Original languageEnglish (US)
Pages (from-to)180-190
Number of pages11
JournalGlia
Volume41
Issue number2
DOIs
StatePublished - Jan 15 2003
Externally publishedYes

Keywords

  • Astroglia
  • CNS injury
  • Endothelin
  • Glia
  • Regeneration

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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