GLIAL-CELL RESPONSES, COMPLEMENT, AND CLUSTERIN IN THE CENTRAL-NERVOUS-SYSTEM FOLLOWING DORSAL-ROOT TRANSECTION

We have examined the glial cell response, the possible expression of c ompounds associated with the complement cascade, including the putativ e complement inhibitor clustering and their cellular association durin g Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activit y after rhizotomy, an exclusive involvement of microglia in this proli feration after peripheral nerve injury, but, in addition, a small frac tion of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after r hizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immu noglobulin G (IgG) deposition or complement expression in the spinal c ord dorsal horn, dorsal funiculus, or gracile nucleus. This is in mark ed contrast to the situation after peripheral nerve injury, which appe ars to activate the entire complement cascade in the vicinity of the c entral sensory processes. Clusterin, a multifunctional protein with co mplement inhibitory effects, was markedly upregulated in the dorsal fu niculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocy tes, possibly reflecting a degeneration process in these cells. The fi ndings suggest that 1) complement expression by microglial cells is in timately associated with IgG deposition; 2) axotomized neuronal perika rya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expres sion following neuronal injury but participates in regulating the stat e of oligodendrocytes during Wallerian degeneration. (C) 1998 Wiley-Li ss, Inc.