PDF(Pubmed)
Abstract：
UNASSIGNED: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes.
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.
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.
摘要：
■缺血性中风（IS）是世界上导致死亡和残疾的主要原因之一，饮酒已成为IS的独立危险因素。血脑屏障(BBB)功能障碍和神经炎症是脑缺血/再灌注(I/R)损伤的核心,周细胞在结构和功能中起着至关重要的作用。本研究旨在探讨长期饮酒对IS的影响以及周细胞的潜在机制。
■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。
■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。
