Abstracts

The complement cascade has been suggested to be involved in the inflammatory responses observed in a variety of disorders of the central nervous system. Recent evidence suggests that complement activation may contribute to seizure activity and promote neurodegeneration. We investigated the possible involvement of the complement cascade during epileptogenesis in a rat model of temporal lobe epilepsy (TLE) and in the chronic phase of spontaneous seizures in both experimental as well as human TLE., RNA was obtained from three different brain regions (CA3, entorhinal cortex and cerebellum) at three different time points (1 day =acute phase; and 1 week = latent phase; 3-4 months = chronic epileptic phase) after electrically induced status epilepticus (SE) in rat. Gene expression analysis was performed using the Affymetrix Gene Chip System (230A). The immunohistochemical pattern of C1q, C3c and C3d was assessed in human hippocampal specimens from controls and medically intractable TLE with or without hippocampal sclerosis (HS)., Genes involved in the complement pathway (e.g. C1qa, C1qc, C3, C4a, Cfh) were upregulated after induction of SE in rat and remained elevated in the chronic phase. C1qa and C1qc were already induced in the acute phase. C3, C4a and C8b were induced in the latent phase and showed the highest expression at the end of the latent period. In human TLE with HS, glial expression of C1q, C3c and C3d was observed particularly within regions where neuronal cell loss occurs (e.g. CA1 and hilus)., Our data indicate that within the immune response the complement activation represents a prominent process during epileptogenesis. The persistence of complement activation is supported by the data on human HS specimen showing increased expression of complement factors in activated glial cells. Although the complement system may be useful in eliminating aggregated and harmful proteins associated with epilepsy, abnormal activation of the complement system can also have damaging effects through activation of inflammatory processes., (Supported by National Epilepsy Fund - [ldquo]Power of the Small[rdquo]/ Hersenstichting Nederland (NEF 02-10; NEF 05-11, E. Aronica and K. Boer; 03-03 J.A. Gorter).)