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利用11.7T磁共振成像T1映射评估高血压性脑小血管病中的血脑屏障损伤及微血管病理变化。

Assessment of blood-brain barrier injury in hypertensive CSVD by 11.7TMR T1mapping and microvascular pathologic changes.

作者信息

Tu Zhilan, Xi Yan, Zhang Yuwen, Jin Pengpen, Yang Hualan, Li Chao, Zhang Zengyu, Wang He, Hou Shuangxing

机构信息

Department of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China.

Department of Radiology, Shanghai TCM-Integrated Hospital, 230 Baoding Road, Shanghai, 200000, China.

出版信息

Metab Brain Dis. 2024 Dec 16;40(1):66. doi: 10.1007/s11011-024-01483-9.

Abstract

We used spontaneously hypertensive rats (SHR) as a hypertensive cerebral small vessel disease (CSVD) model to quantify blood-brain barrier (BBB) disruption by 11.7TMR T1mapping and to investigate white matter lesions and microangiopathy in CSVD. Male SHR were used as a hypertensive CSVD animal model and normotensive Wistar-Kyoto rats (WKY) were used as a control model. After 18 weeks, the rats did the Morris water maze test were evaluated, blood-brain barrier (BBB) integrity were evaluated by using Bruker 11.7T MR T1 mapping. ITK-SNAP software was used to measure hippocampal volume. Then, pathological analysis was carried out on rats, myelin integrity, vascular permeability and microvessel density were assessed by immunohistochemistry. Our data showed that hypertensive CSVD model exhibited decreased memory function, BBB leakage could be detected differently in different brain regions, and T1 values of the hippocampus showed the greatest drop than other areas. Furthermore, the pathological changes in small vessels were more extensive, average optical density of myelin basic protein (MBP) in the white matter of SHR group was significantly reduced, moreover, VEGFR2 immunoreactivity scores (IRS) and CD34-assessed MVD in SHR group were significantly higher than WKY group. We find different parts of the brain tissues have different degrees of BBB leakage, hippocampal atrophy and hippocampal volume were decreased in hypertensive CSVD by using T1 Mapping. Loss of myelin integrity, vascular permeability increased and microangiopathy may contribute to hypertensive-related BBB functional deficits in CSVD model.

摘要

我们使用自发性高血压大鼠(SHR)作为高血压性脑小血管病(CSVD)模型,通过11.7T磁共振成像T1映射来量化血脑屏障(BBB)破坏情况,并研究CSVD中的白质病变和微血管病变。雄性SHR被用作高血压CSVD动物模型,正常血压的Wistar-Kyoto大鼠(WKY)被用作对照模型。18周后,对进行莫里斯水迷宫测试的大鼠进行评估,使用布鲁克11.7T磁共振成像T1映射评估血脑屏障(BBB)完整性。使用ITK-SNAP软件测量海马体积。然后,对大鼠进行病理分析,通过免疫组织化学评估髓鞘完整性、血管通透性和微血管密度。我们的数据表明,高血压CSVD模型表现出记忆功能下降,不同脑区可检测到不同程度的BBB渗漏,海马的T1值下降幅度比其他区域最大。此外,小血管的病理变化更广泛,SHR组白质中髓鞘碱性蛋白(MBP)的平均光密度显著降低,而且,SHR组中VEGFR2免疫反应性评分(IRS)和CD34评估的微血管密度(MVD)显著高于WKY组。我们发现,通过T1映射发现高血压CSVD模型中脑组织不同部位存在不同程度的BBB渗漏、海马萎缩且海马体积减小。髓鞘完整性丧失、血管通透性增加和微血管病变可能导致CSVD模型中与高血压相关的BBB功能缺陷。

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