COMPLEMENT AND CLUSTERIN IN THE SPINAL-CORD DORSAL HORN AND GRACILE NUCLEUS FOLLOWING SCIATIC-NERVE INJURY IN THE ADULT-RAT

We provide evidence for activation of the complement cascade in the do rsal horn of the spinal cord and in the gracile nucleus in the brainst em following sciatic nerve transection in the adult rat. Immunocytoche mical analyses showed immunoreactivity for endogenous immunoglobulin G as shown by immunostaining with F(ab')(2) antibodies, as well as comp lement factors C1, Clq, C3, C3d and C9 in the appropriate central term ination areas of the injured sciatic nerve. Results from double labell ing immunocytochemistry showed a strong association between immunoglob ulin and complement factors on the one hand and reactive microglia on the other. However, some complement immunoreactivity was also found in the neuropil, possibly representing secreted complement. In situ hybr idization with an oligonucleotide probe showed a marked increase in C3 messenger RNA, indicating local synthesis of C3 protein. In parallel with activation of complement, there was an increased immunoreactivity for the putative complement inhibitor clusterin, which co-localized w ith glial fibrillary acidic protein-positive astrocytes. In situ hybri dization showed an increased labelling of clusterin messenger RNA. The se findings indicate that complement activation and up-regulation of c omplement inhibitors are prominent central responses to peripheral sen sory nerve injury. These responses may therefore be important elements underlying so-called transganglionic degenerative changes in primary sensory axons and terminals.