Inhibiting nuclear factor-κB at different stages after intracerebral hemorrhage can influence the hemorrhage-induced brain injury in experimental models in vivo

• Published in: Brain research bulletin Vol. 155; pp. 159 - 165
• Main Authors: Zhang, Zeli, Song, Yan, Li, Feng, Xu, Zhenkuan, Huang, Qibing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• Subjects: Cell death; Inhibition; Intracerebral hemorrhage; Nuclear factor-kappaB; Subunits; NF-κB; TUNEL; TNF-α; Cell death; EMSA; PDTC; Subunits; Nuclear factor-kappaB; Inhibition; IL-1β; Intracerebral hemorrhage; ICH
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2019.12.010

•PDTC can inhibite NF-κB activation at the early and late stages after ICH.•NF-κB inhibition at the early stage was due to p65, and late stage c-Rel.•Inhibiting p65 expression at the early stage after ICH can reduce cell death.•Inhibiting c-Rel expression at the late stage after ICH can promote cell death.•Inhibiting NF-κB at different stages after ICH can influence the prognosis. Nuclear factor-κB (NF-κB) is a critical regulator of inflammatory responses after ICH, and different subunits may have different influences on the cell death and prognosis. The aim of the present study is to clarify whether the prognosis can be influenced by inhibiting NF-κB activation and subunits expression using PDTC at different stages after ICH. Rats were divided into sham group, ICH group, early interference group and late interference group. At preset time points after ICH, the ipsilateral striatum and tissue around was obtained for detection of NF-κB activation, cell death, and expression of caspase-3, bcl-2, and NF-κB subunits, to evaluate of the effect of PDTC. NF-κB subunit p65 mainly expressed at the early stage after ICH, and c-Rel at the late stage. NF-κB activation can be inhibited at the early stage after ICH by administrating PDTC at 10 min, 1d and 2d after ICH, and at the late stage at 6d,7d and 8d. NF-κB activation inhibition at the early stage was due to p65, and c-Rel at the late stage. Inhibiting p65 expression at the early stage after ICH can reduce the apoptotic factor caspase-3 expression and cell death, and raise the antiapoptotic factor bcl-2. Meanwhile, inhibiting c-Rel expression at the late stage after ICH can lead to the opposite result. Measures of inhibiting NF-κB subunits can be performed to influence the secondary brain damage and prognosis of ICH. We can also speculate that early inhibition of p65 expression and late promotion of c-Rel expression may be a more efficient method to improve the prognosis of ICH.