文献类型：期刊文献

英文题名：Vascular Cognitive Impairment Caused by Cerebral Small Vessel Disease Is Associated with the TLR4 in the Hippocampus

作者：Gao, Fulin[1,3];Jing, Yuhong[2];Zang, Peixi[1];Hu, Xiaojuan[1];Gu, Cheng[1];Wu, Ruipeng[1];Chai, Bingyan[3];Zhang, Yi[1]

第一作者：Gao, Fulin

通信作者：Zhang, Y[1]

机构：[1]Gansu Prov Hosp, Dept Neurol, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Sch Basic Med Sci, Inst Anat & Histol & Embryol, Neurosci, Lanzhou, Gansu, Peoples R China;[3]Gansu Univ Tradit Chinese Med, Sch Clin Med, Lanzhou, Gansu, Peoples R China

第一机构：Gansu Prov Hosp, Dept Neurol, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Neurol, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2019

卷号：70

期号：2

起止页码：561

外文期刊名：JOURNAL OF ALZHEIMERS DISEASE

收录：;Scopus(收录号：2-s2.0-85069935483);WOS:【SCI-EXPANDED(收录号:WOS:000476865800021)】；

基金：This work was supported by GSWSKY-2015-06 of the Gansu Provincial Health industry research projects. The authors are thankful to Peixi Zang and Xiaojuan Hu for their experimental assistance and Professor Jing for assistance with writing guidance and review. We thank Institute of Anatomy, Neuroscience, School of Basic Medical Sciences, Lanzhou University for their invaluable contribution to experimental guidance.

语种：英文

外文关键词：Cerebral small vessel disease; glial cell; neuroinflammation; spontaneous hypertension rats; toll-like receptor 4; vascular cognitive impairment

摘要：Background: Cerebral small vessel disease (CSVD) can lead to leukodystrophy and cognitive impairment. The inflammatory response mediated by Toll-like receptor 4 (TLR4) is involved in the pathological process of CSVD, but the roles of TLR4 in vascular cognitive impairment (VCI) following CSVD are not clear. Objective: To explore the roles and mechanisms of TLR4 in the development of VCI. Methods: Male spontaneous hypertension rats (SHR) and Wistar Kyoto rats (WKY) were monitored for blood pressure (BP). The spatial learning and memory were assessed every 6 weeks using Morris water maze (MWM). Blood samples from femoral artery were collected and serum was isolated. Cerebral white matter damage was evaluated using a 3.0T magnetic resonance imaging (MRI) every 12 weeks. After 35 weeks, all rats were decapitated, and the expression of TLR4 in the hippocampus was determined using western blot. The number of positive cells of TLR4, active astrocyte and microglia in hippocampus were measured using immunohistochemistry and immunofluorescence. Results: Compared with WKY, the BP of SHR was maintained at a high level. Spatial learning and memory declined. IL-1 beta and TNF-alpha levels were elevated. Cranial coronal scanning with T2-weighted MRI showed high signal intensity in corpus callosum and external capsule of SHR. Furthermore, in SHR, the expression of TLR4, GFAP, and Iba1 in the hippocampus were increased. Conclusion: Hypertension can cause small vascular damage and partial white matter degeneration in the brain. SHR showed cognitive impairment with increasing age. High expression of TLR4 and glial cell response in hippocampus is one of the key mechanisms of this disease.