Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS
Version of Record online: 28 DEC 2002
Copyright © 2003 Wiley-Liss, Inc.
Volume 41, Issue 2, pages 180–190, 15 January 2003
How to Cite
Rogers, S. D., Peters, C. M., Pomonis, J. D., Hagiwara, H., Ghilardi, J. R. and Mantyh, P. W. (2003), Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS. Glia, 41: 180–190. doi: 10.1002/glia.10173
- Issue online: 28 DEC 2002
- Version of Record online: 28 DEC 2002
- Manuscript Accepted: 4 SEP 2002
- Manuscript Received: 31 MAY 2002
- Merit Review from the Veterans Administration
- American Paralysis Association
- National Institutes of Health. Grant Numbers: NS23970, DA11986
- CNS injury
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. GLIA 41:180–190, 2003. © 2003 Wiley-Liss, Inc.