The correlation between accumulation of amyloid beta with enhanced neuroinflammation and cognitive impairment after intraventricular hemorrhage
The correlation between accumulation of amyloid beta with enhanced neuroinflammation and cognitive impairment after intraventricular hemorrhage
复制标题
β淀粉样蛋白的积累与脑室内出血后神经炎症增强和认知障碍之间的相关性。
DOI：
10.3171/2018.1.jns172938
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发表时间：
2019-07-01
影响因子：
4.1
通讯作者：
Chen, Liang
中科院分区：
文献类型：
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作者：
Jiang, Conglin;Zou, Xiang;Chen, Liang
目的脑室内出血(IVH)约占脑出血的40%，且与死亡率增加和功能预后不良有关。认知功能障碍是其并发症之一，是由多种病理改变引起的。淀粉样β蛋白(Aβ)的堆积和神经炎症，以及阿尔茨海默病样的病理，可能导致认知障碍。铁是血红蛋白的降解产物，与Aβ相关。在这项研究中，作者研究了在IVH大鼠模型中Aβ积聚与增强的神经炎症和认知障碍的相关性。另设9只大鼠为对照组。用Morris水迷宫和T迷宫奖赏交替测验评定认知功能。检测A-β蓄积、神经炎症和c-jun氨基末端激酶活性等生物标志物。注血组可见Aβ积聚，且储铁蛋白铁蛋白与Aβ呈同位相关。β位点淀粉样前体蛋白裂解酶1(BACE1)活性升高。在海马CA1、CA2、CA3和齿状回区域观察到小胶质细胞和星形胶质细胞增生，并伴有促炎细胞因子肿瘤坏死因子-α和白介素1的升高。结论β积聚和神经炎症反应增强在脑出血后认知损害中起一定作用。一种潜在的治疗方法需要进一步研究。
OBJECTIVEIntraventricular hemorrhage (IVH) is found in approximately 40% of intracerebral hemorrhages and is associated with increased mortality and poor functional outcome. Cognitive impairment is one of the complications and occurs due to various pathological changes. Amyloid beta (Aβ) accumulation and neuroinflammation, and the Alzheimer disease-like pathology, may contribute to cognitive impairment. Iron, the degradation product of hemoglobin, correlates with Aβ. In this study, the authors investigated the correlation between Aβ accumulation with enhanced neuroinflammation and cognitive impairment in a rat model of IVH.METHODSNine male Sprague-Dawley rats underwent an intraventricular injection of autologous blood. Another 9 rats served as controls. Cognitive function was assessed by the Morris water maze and T-maze rewarded alternation tests. Biomarkers of Aβ accumulation, neuroinflammation, and c-Jun N-terminal kinase (JNK) activation were examined.RESULTSCognitive function was impaired in the autologous blood injection group compared with the control group. In the blood injection group, Aβ accumulation was observed, with a co-located correlation between iron storage protein ferritin and Aβ. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity was elevated. Microgliosis and astrogliosis were observed in hippocampal CA1, CA2, CA3, and dentate gyrus areas, with elevated proinflammatory cytokines tumor necrosis factor-α and interleukin-1. Protein levels of phosphorylated JNK were increased after blood injection.CONCLUSIONSAβ accumulation and enhanced neuroinflammation have a role in cognitive impairment after IVH. A potential therapeutic method requires further investigation.