Complement activation in experimental and human temporal lobe epilepsy.
We investigated the involvement of the complement cascade during epileptogenesis in a rat model of temporal lobe epilepsy (TLE), and in the chronic epileptic phase in both experimental as well as human TLE. Previous rat gene expression analysis using microarrays indicated prominent activation of the classical complement pathway which peaked at 1 week after SE in CA3 and entorhinal cortex. Increased expression of C1q, C3 and C4 was confirmed in CA3 tissue using quantitative PCR at 1 day, 1 week and 3-4 months after status epilepticus (SE). Upregulation of C1q and C3d protein expression was confirmed mainly to be present in microglia and in a few hippocampal neurons. In human TLE with hippocampal sclerosis, astroglial, microglial and neuronal (5/8 cases) expression of C1q, C3c and C3d was observed particularly within regions where neuronal cell loss occurs. The membrane attack protein complex (C5b-C9) was predominantly detected in activated microglial cells. The persistence of complement activation could contribute to a sustained inflammatory response and could destabilize neuronal networks involved.
Aronica
E
E
Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Boer
K
K
van Vliet
E A
EA
Redeker
S
S
Baayen
J C
JC
Spliet
W G M
WG
van Rijen
P C
PC
Troost
D
D
da Silva
F H Lopes
FH
Wadman
W J
WJ
Gorter
J A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D015922:Complement C1q / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015932:Complement C3c / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015933:Complement C3d / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050776:Complement C5b / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006624:Hippocampus / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D012333:RNA, Messenger; D015922:Complement C1q; D015932:Complement C3c; D015933:Complement C3d; D050776:Complement C5b; D003165:Complement System Proteins