UNASSIGNED: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed.
UNASSIGNED: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol.
UNASSIGNED: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.
■长期饮酒后发生短暂性大脑中动脉阻塞卒中(EtOHtMCAO)的大鼠模型和酒精预处理的氧葡萄糖剥夺/复氧(OGD/R)的细胞模型。
■梗死体积加重,神经学评分,与tMCAO组相比,EtOH+tMCAO组观察到BBB破坏,免疫荧光染色显示,缺血半暗带周细胞NLPR3炎性体激活增加。体外,OGD/R后酒精预处理的周细胞死亡率和LDH释放升高,通过Westernblotting和qPCR检测NLRP3炎性小体的扩增表达。酒精预处理激活TLR4/NF-κB通路,用TLR4小干扰RNA(siRNA)转染周细胞以阻断TLR4信号传导显着抑制了NLRP3炎性体的过度激活。在大鼠中注射TAK-242减轻了酒精引起的神经损害。
■长期酒精预处理可通过周细胞TLR4/NF-κB信号通路激活NLRP3炎症小体,加重缺血性卒中所致脑损伤。