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 complement expression. The main source of complement in peripheral nerve injury and toxic ricin degeneration appears to be microglia. Brain contusion is associated with complement activation. Some of the complement in this situation may derive from plasma, because the blood-brain barrier is disrupted. Clusterin expression is increased in astrocytes along with their activation in the vicinity of lesioned neurons. In addition, axotomized motorneurons show a marked clusterin upregulation. A relationship between clusterin and cell death is suggested by the prominent aggregation of clusterin in neuronal perikarya destroyed by the effects of toxic ricin, as well as by the neosynthesis of clusterin in apparently degenerating nonneuronal cells, presumed to be oligodendrocytes. Our findings indicate that the expression of complement and clusterin are prominent features of neural degeneration and regeneration, as it is in Alzheimer's disease brains as well. The nerve injury conditions described, therefore, offer attractive experimental models to elucidate the roles of these molecular components in neurodegenerative disorders, thereby providing useful insights into potentially new therapeutic approaches in these conditions.