Berberine Protects against Neurological Impairments and Blood-Brain Barrier Injury in Mouse Model of Intracerebral Hemorrhage.

IF 2.2 4区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuroimmunomodulation Pub Date : 2022-01-01 DOI:10.1159/000520747

Xiuwen Wu, Xiaopeng Liu, Liang Yang, Yuanyu Wang

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引用次数: 6

Abstract

Background: Elevation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signaling can suppress intracerebral hemorrhage (ICH)-induced neurological impairments. As an isoquinoline alkaloid, Berberine exerts neuroprotective effects in neurological disease models with activated AMPK/PGC1α signaling.

Aim: We aim to study the effect of Berberine on ICH-induced brain injury and explore the potential molecular mechanism.

Methods: ICH model was established in mice through intracerebral injection of autologous whole blood, followed by treatment with Berberine. Neurological impairments were assessed by the modified neurological severity score and behavioral assays. Brain edema and blood-brain barrier (BBB) integrity were assessed by water content in the brain, amount of extravasated Evans blue, and BBB tight junction components. Neuroinflammatory responses were assessed by inflammatory cytokine levels. AMPK/PGC1α signaling was examined by AMPK mRNA expression and phosphorylated AMPK and PGC1α protein levels.

Results: Berberine (200 mg/kg) attenuated ICH-induced neurological deficits, motor and cognitive impairment, and BBB disruption. Berberine also suppressed ICH-induced inflammatory responses indicated by reduced production of inflammatory cytokines. Finally, Berberine drastically elevated AMPK/PGC1α signaling in the hemisphere of ICH mice.

Conclusion: Our findings suggest that Berberine plays an important neuroprotective role against ICH-induced neurological impairments and BBB injury, probably by inhibition of inflammation and activation of AMPK/PGC1α signaling.

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小檗碱对脑出血小鼠模型的神经损伤和血脑屏障损伤的保护作用。

背景:amp活化蛋白激酶(AMPK)/过氧化物酶体增殖物活化受体-γ共激活因子-1α (PGC1α)信号的升高可以抑制脑出血(ICH)诱导的神经功能损伤。作为一种异喹啉生物碱，小檗碱在激活AMPK/PGC1α信号通路的神经系统疾病模型中发挥神经保护作用。目的:研究小檗碱对ich所致脑损伤的作用，并探讨其可能的分子机制。方法:采用自体全血脑内注射建立小鼠脑出血模型，并给予小檗碱治疗。通过改进的神经严重程度评分和行为测试评估神经损伤。脑水肿和血脑屏障(BBB)完整性通过脑含水量、外渗埃文斯蓝量和血脑屏障紧密连接成分来评估。通过炎症细胞因子水平评估神经炎症反应。通过AMPK mRNA表达和磷酸化AMPK和PGC1α蛋白水平检测AMPK/PGC1α信号通路。结果:小檗碱(200 mg/kg)可减轻ich引起的神经功能缺损、运动和认知障碍以及血脑屏障紊乱。小檗碱还抑制ich诱导的炎症反应，表明炎症细胞因子的产生减少。最后，小檗碱显著提高脑出血小鼠脑半球的AMPK/PGC1α信号通路。结论:小檗碱可能通过抑制炎症和激活AMPK/PGC1α信号通路，对ich诱导的神经损伤和血脑屏障损伤具有重要的神经保护作用。

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来源期刊

Neuroimmunomodulation 医学-免疫学

CiteScore

3.60

自引率

4.20%

发文量

审稿时长

>12 weeks

期刊介绍： The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.