White-matter abnormalities and cognitive dysfunction are linked to astrocyte activation in sickle mice.
White-matter abnormalities and cognitive dysfunction are linked to astrocyte activation in sickle mice.
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DOI：
10.1093/pnasnexus/pgad149
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发表时间：
2023-05
期刊：
影响因子：
--
通讯作者：
Novelli, Enrico M.
中科院分区：
文献类型：
--
作者：
Hazra, Rimi;Pu, Hongjian;Foley, Lesley M.;Little-Ihrig, Lynda;Hitchens, T. Kevin;Ghosh, Samit;Ofori-Acquah, Solomon F.;Hu, Xiaoming;Novelli, Enrico M.
镰状细胞病（SCD）的白质损伤包括弥散张量成像（DTI）诊断的无症状性脑梗死，这是SCD儿童认知功能障碍相关的并发症。白质损伤和认知功能障碍之间的联系尚未完全阐明。本研究的目的是确定SCD中的脑血管病变和认知功能是否与人类镰状血红蛋白S（SS）纯合子的人源化Townes' SCD小鼠和人类正常血红蛋白A（AA）纯合子的对照小鼠中的神经轴突损伤和星形胶质细胞活化相关。对小鼠进行MRI和DTI以及认知测试，并对它们大脑的组织切片进行染色以评估微结构组织损伤、神经轴突损伤和星形胶质细胞活化。部分各向异性，显示微结构脑血管异常的白色物质的DTI，与神经元脱髓鞘在SS小鼠大脑中显着相关。在新物体识别测试中，与AA对照小鼠相比，SS小鼠的学习和记忆功能降低，辨别指数显著降低。SS小鼠的神经轴突损伤与神经认知功能受损和星形胶质细胞活化同步相关。星形胶质细胞功能和神经元之间的相互作用可能调节SCD的认知表现。
White-matter injury in sickle-cell disease (SCD) includes silent cerebral infarction diagnosed by diffusion tensor imaging (DTI), a complication associated with cognitive dysfunction in children with SCD. The link between white-matter injury and cognitive dysfunction has not been fully elucidated. The goal of this study was to define whether cerebrovascular lesions and cognitive function in SCD are linked to neuroaxonal damage and astrocyte activation in humanized Townes’ SCD mice homozygous for human sickle hemoglobin S (SS) and control mice homozygous for human normal hemoglobin A (AA). Mice underwent MRI with DTI and cognitive testing, and histology sections from their brains were stained to assess microstructural tissue damage, neuroaxonal damage, and astrocyte activation. Fractional anisotropy, showing microstructural cerebrovascular abnormalities identified by DTI in the white matter, was significantly associated with neuronal demyelination in the SS mouse brain. SS mice had reduced learning and memory function with a significantly lower discrimination index compared with AA control mice in the novel object recognition tests. Neuroaxonal damage in the SS mice was synchronously correlated with impaired neurocognitive function and activation of astrocytes. The interplay between astrocyte function and neurons may modulate cognitive performance in SCD.
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DOI：
10.1177/0271678x211028680
发表时间：
2021-11
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Pu H;Ma C;Zhao Y;Wang Y;Zhang W;Miao W;Yu F;Hu X;Shi Y;Leak RK;Hitchens TK;Dixon CE;Bennett MV;Chen J
通讯作者：
Chen J
DOI：
10.1007/978-1-4939-8994-2_10
发表时间：
2019-01-01
期刊：
PRE-CLINICAL MODELS
影响因子：
--
作者：
Kraeuter, Ann-Katrin;Guest, Paul C.;Sarnyai, Zoltan
通讯作者：
Sarnyai, Zoltan
DOI：
10.4103/ijri.ijri_166_17
发表时间：
2018-07
期刊：
The Indian journal of radiology & imaging
影响因子：
--
作者：
Issar P;Nehra M;Singh G;Issar SK
通讯作者：
Issar SK
影响因子：
20.3
作者：
Bernaudin, Francoise;Verlhac, Suzanne;Pondarre, Corinne
通讯作者：
Pondarre, Corinne
影响因子：
8.3
作者：
Kawadler, Jamie M.;Kirkham, Fenella J.;Clark, Chris A.
通讯作者：
Clark, Chris A.