A Comparison of the Changes in the Non-Neuronal Cell Populations of the Superior Cervical Ganglia following Decentralization and Axotomy Rebecca C. Schreiber, Stacey A. Vaccariello, Kristen Boeshore, Annette M. Shadiack,* Richard E. Zigmond Department of Neurosciences, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106-4975 Received 26 February 2002; accepted 15 May 2002 ABSTRACT: Transecting the axons of neurons in the adult superior cervical ganglion (SCG; axotomy) re- sults in the survival of most postganglionic neurons, the influx of circulating monocytes, proliferation of satellite cells, and changes in neuronal gene expression. In contrast, transecting the afferent input to the SCG (decentralization) results in nerve terminal degeneration and elicits a differ- ent pattern of gene expression. We examined the effects of decentralization on macrophages in the SCG and com- pared the results to those previously obtained after axo- tomy. Monoclonal antibodies were used to identify infil- trating (ED1) and resident (ED2) macrophages, as well as macrophages expressing MHC class II molecules (OX6). Normal ganglia contained ED2 cells and OX6 cells, but few infiltrating macrophages. After decentraliza- tion, the number of infiltrating ED1 cells increased in the SCG to a density about twofold greater than that previ- ously seen after axotomy. Both the densities of ED2 and OX6 cells were essentially unchanged after decentraliza- tion, though a large increase in OX6 cells occurred after axotomy. Proliferation among the ganglion’s total non- neuronal cell population was examined and found to in- crease about twofold after decentralization and about four- fold after axotomy. Double-labeling experiments indicated that some of these proliferating cells were macrophages. After both surgical procedures, the percentage of proliferating ED2 macrophages increased, while neither procedure al- tered the proliferation of ED1 macrophages. Axotomy, though not decentralization, increased the proliferation of OX6 cells. Future studies must address what role(s) infil- trating and/or resident macrophages play in regions of decen- tralized and axotomized neurons and, if both are involved, whether they play distinct roles. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 68 –79, 2002 Keywords: axotomy; decentralization; MHC class II; macrophage; superior cervical ganglion; peripheral nerve injury INTRODUCTION After a peripheral nerve lesion (e.g., resulting from nerve transection, ligation, crushing, or freezing), a series of responses occur both in the injured neurons themselves and in nearby non-neuronal cells. For ex- ample, following lesioning of the sciatic nerve (a mixed nerve containing axons of motor, sensory and sympathetic neurons), a number of changes occur in the nerve trunk distal to the site of lesion. These changes include degeneration of the severed axons (Stoll and Muller, 1999), infiltration of circulating monocytes that differentiate into macrophages (Ols- son and Sjostrand, 1969; Stoll and Muller, 1986; Perry et al., 1987; Clemence et al., 1989), and prolif- eration of both myelin-forming and nonmyelin-form- ing Schwann cells (Clemence et al., 1989). The main function attributed to macrophages in this context is * Current address: Palatin Technologies Inc., 4-C Cedar Brook Drive, Cranbury, NJ 08512. Correspondence to: R. E. Zigmond (rez@po.cwru.edu). Contract grant sponsor: NIH; contract grant number: NS 17512. Contract grant sponsor: NIH; contract grans number: T32NS07118 (to A.M.S.). Contract grant sponsor: National Institute of Neurological Dis- ease and Stroke; contract grant numbers: NS17512 and NS12651. © 2002 Wiley Periodicals, Inc. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/neu.10093 68