title: Nuclear factor-kappa B activity regulates brain expression of P-glycoprotein in the kainic acid-induced seizure rats.
abstract: This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA-) induced seizure rats. Male SD rats were divided into saline control group (NS group), KA induced epilepsy group (EP group), and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group) or with dexamethasone (DEX group). No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.
authors.affiliation: Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, 264 Guangzhou Road, Nanjing, Jiangsu 210009, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Di
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yu-kui
authors.initials: YK
authors.lastname: Yan
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Zhang
authors.forename: Ying-dong
authors.initials: YD
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016328:NF-kappa B; D051996:Transcription Factor RelA; D007608:Kainic Acid