COMPLEMENT AND CLUSTERIN IN THE INJURED NERVOUS-SYSTEM

Peripheral nerve injury and neuronal degeneration resulting from toxic ricin induce activation of the classical pathway of complement close to the injured motorneuron perikarya or sensory terminals. In contrast , degeneration of central myelinated fibers is not accompanied by comp lement expression. The main source of complement in peripheral nerve i njury and toxic ricin degeneration appears to be microglia. Brain cont usion is associated with complement activation. Some of the complement in this situation may derive from plasma, because the blood-brain bar rier is disrupted. Clusterin expression is increased in astrocytes alo ng with their activation in the vicinity of lesioned neurons. In addit ion, axotomized motorneurons show a marked clusterin upregulation. A r elationship between clusterin and cell death is suggested by the promi nent aggregation of clusterin in neuronal perikarya destroyed by the e ffects of toxic ricin, as well as by the neosynthesis of clusterin in apparently degenerating nonneuronal cells, presumed to be oligodendroc ytes. Our findings indicate that the expression of complement and clus terin are prominent features of neural degeneration and regeneration, as it is in Alzheimer's disease brains as well. The nerve injury condi tions described, therefore, offer attractive experimental models to el ucidate the roles of these molecular components in neurodegenerative d isorders, thereby providing useful insights into potentially new thera peutic approaches in these conditions.