Beta-adrenergic receptor blockade suppresses glial scar formation.
Several laboratories have shown that isoproterenol induces or accelerates cell process formation in primary astrocyte cultures. These observations, together with the demonstration of beta-adrenergic receptors in astrocytes isolated from adult rat brain, led us to test the hypothesis that beta-antagonists prevent astrocyte hypertrophy in the injured spinal cord. Since blood-borne macrophages express beta-adrenergic receptors and release cytokines acting on glial cells, we avoided physical trauma and induced glial scar formation indirectly by injecting the cytotoxic ligand Ricinus communis into the sciatic nerve. Seven days later sections of the lumbar spinal cord in regions of motor neuron degeneration were processed for glial fibrillary acidic protein (GFAP) immunocytochemistry. Astrocyte hypertrophy was evaluated by optical density measurements of immunolabeled GFAP. Seven days after ricin treatment there is a mean increase of GFAP in the ventral horn of 11.8 +/- 4.4% (P < 0.0001) compared to the intact side. When L-propranolol is continuously infused from a subcutaneously implanted osmotic pump at a concentration calculated to produce a free plasma level of 4.4 nM, the GFAP increase is only 3.2 +/- 3%, reflecting a 73% reduction in astrocyte hypertrophy (P < 0.001). Receptor autoradiography with the ligand [125I]iodocyanopindolol showed a 26% increase in beta-adrenergic receptor density on the gliotic side. After propranolol treatment, there was only a 3.5% increase in ventral horn beta-adrenergic receptor density in the region of the glial scar.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.
J
J
Sutin
R
R
Griffith
D000818:Animals; D001345:Autoradiography; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012276:Ricin / Q000633:toxicity*; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D005904:Glial Fibrillary Acidic Protein; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D012276:Ricin; D011433:Propranolol; D010869:Pindolol; D004837:Epinephrine