Complement anaphylatoxin C3a is selectively protective against NMDA-induced neuronal cell death

The anaphylatoxin C3a is a potent inflammatory polypeptide released at site s of complement activation. To test whether C3a might alter neuronal outcom e following an ischemic insult, we determined the effects of purified human C3a on murine primary cortical cell cultures exposed to apoptotic or excit otoxic paradigms. C3a prevented neither serum deprivation-induced apoptotic neuronal death, nor AMPA/kainate-mediated excitotoxicity. However, in mixe d cultures of neurons and astrocytes, Ca dose-dependently protected neurons against NMDA toxicity (47% neuroprotection using 100 nM C3a, p< 0.01, n = 12). The neuroprotective effect of C3a was observable only in the presence of astrocytes. These observations suggest that C3a is involved in excitotox icity-mediated neuronal death through astrocyte stimulation and extend its role beyond immune functions. NeuroReport 12:289-293 (C) 2001 Lippincott Wi lliams & Wilkins.