BETA-ADRENERGIC RECEPTORS REGULATE ASTROGLIOSIS AND CELL-PROLIFERATION IN THE CENTRAL-NERVOUS-SYSTEM IN-VIVO

Astrocytes express several cell surface receptors including the beta(2 )-adrenergic receptor. To explore whether beta-adrenergic receptors (b eta-ARs) directly regulate astrogliosis and glial scar formation, we e valuated the effects of beta-AR activation and blockade on astrocyte h ypertrophy and cell proliferation in rabbit optic nerves in vivo. Arti ficial cerebrospinal fluid (CSF), isoproterenol (ISO; a beta-agonist), or propranolol (PROP; a beta-antagonist) were infused via osmotic min ipumps into non-injured and crushed optic nerves for 14 days. Changes in nerve cell numbers and astroglial hypertrophy were monitored by eth idium bromide nuclear staining and glial fibrillary acidic protein (GF AP) immunohistochemistry, respectively. In non-injured nerves infused with CSF or PROP, there were no alterations in GFAP-immunoreactivity o r cell numbers compared to normal optic nerves; however, in non-injure d nerves infused with ISO, there was a significant increase in both GF AP-immunoreactivity and cell number. In crushed optic nerves, there wa s a significant increase in both GFAP-immunoreactivity and cell number compared to normal nerves, and this increase was not altered by infus ion of either CSF or ISO. In contrast, PROP infusion significantly red uced the crush-induced increase in GFAP-immunofluorescence and cell nu mber. These findings suggest that a) beta-AR activation, in the absenc e of injury can promote astroglial hypertrophy and cell proliferation; b) after injury, beta-AR activation drives injury-induced astrogliosi s and cell proliferation; c) astrocyte beta-ARs are maximally stimulat ed after neuronal injury; and d) neuronal regeneration may be influenc ed, both positively and negatively, through the pharmacological manipu lation of glial receptors. (C) 1996 Wiley-Liss, Inc.