Jiang Conglin, Zou Xiang, Zhu Renqing, Shi Yimin, Wu Zehan, Zhao Fan, Chen Liang
1Department of Neurosurgery and.
2National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
J Neurosurg. 2019 Jul 1;131(1):54-63. doi: 10.3171/2018.1.JNS172938. Epub 2018 Jul 20.
Intraventricular 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.
Nine 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.
Cognitive 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.
Aβ accumulation and enhanced neuroinflammation have a role in cognitive impairment after IVH. A potential therapeutic method requires further investigation.
脑室内出血（IVH）约占脑出血的40%，与死亡率增加和功能预后不良相关。认知障碍是并发症之一，由各种病理变化引起。淀粉样β蛋白（Aβ）聚集、神经炎症以及阿尔茨海默病样病理改变可能导致认知障碍。血红蛋白的降解产物铁与Aβ相关。在本研究中，作者在IVH大鼠模型中研究了Aβ聚集与神经炎症增强及认知障碍之间的相关性。
9只雄性Sprague-Dawley大鼠接受脑室内自体血注射。另外9只大鼠作为对照。通过莫里斯水迷宫和T迷宫奖励交替试验评估认知功能。检测Aβ聚集、神经炎症和c-Jun氨基末端激酶（JNK）激活的生物标志物。
与对照组相比，自体血注射组的认知功能受损。在血液注射组中，观察到Aβ聚集，铁储存蛋白铁蛋白与Aβ存在共定位相关性。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增生和星形胶质细胞增生，促炎细胞因子肿瘤坏死因子-α和白细胞介素-1升高。血液注射后，磷酸化JNK的蛋白水平升高。
Aβ聚集和神经炎症增强在IVH后认知障碍中起作用。一种潜在的治疗方法需要进一步研究。
