title: Complement protein 6 deficiency in PVG/c rats does not lead to neuroprotection against seizure induced cell death.
abstract: Since the membrane attack complex (MAC), an end product of the activated complement cascade, has been shown to play a role in neurodegeneration, we investigated to which extent MAC contributes to structural reorganization, neuronal cell death, and seizure development in two rat models for temporal lobe epilepsy. We used the electrically-induced status epilepticus (SE) model and the kindling model in C6-deficient rats (that are unable to form MAC) and wild-type (WT) PVG/c rats. Structural reorganization was investigated using hilar cell counts and mossy fiber sprouting. Seizure development was monitored using electroencephalographic (EEG) recordings. 4 weeks after electrically stimulated SE, hilar cell counts in C6-deficient and WT post-SE rats were significantly decreased compared to an unstimulated control group, but not different between C6-deficient and WT post-SE. Since seizure development was unexpectedly absent in most post-SE rats we assessed epileptogenesis using the kindling rate as main parameter. Kindling development was slightly delayed in C6-deficient rats compared to WT rats. The lack of effect of C6 deficiency on hilar cell death and mossy fiber sprouting after electrically-induced SE or kindling argues against a role of the terminal complement complex in neuronal cell death induced by SE or seizures. A small but significant delay of kindling epileptogenesis suggests a subtle role of MAC in seizure spread. Whether complement components upstream of MAC play a crucial role in neuronal death and/or epileptogenesis needs to be further investigated.
authors.affiliation: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Holtman
authors.forename: E A
authors.initials: EA
authors.lastname: van Vliet
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: E
authors.initials: E
authors.lastname: Aronica
authors.forename: J A
authors.initials: JA
authors.lastname: Gorter
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death; D003183:Complement C6 / Q000172:deficiency*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007696:Kindling, Neurologic; D019599:Mossy Fibers, Hippocampal / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D012640:Seizures / Q000473:pathology / Q000503:physiopathology*
chemical_list: D003183:Complement C6; D015938:Complement Membrane Attack Complex