Department of Neurology, Gansu Provincial Hospital, Lanzhou City, Gansu Province, PR China.
School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou City, Gansu Province, PR China.
J Alzheimers Dis. 2019;70(2):563-572. doi: 10.3233/JAD-190240.
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.
To explore the roles and mechanisms of TLR4 in the development of VCI.
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.
Compared with WKY, the BP of SHR was maintained at a high level. Spatial learning and memory declined. IL-1β and TNF-α 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.
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.
脑小血管病（CSVD）可导致脑白质病变和认知功能障碍。Toll 样受体 4（TLR4）介导的炎症反应参与 CSVD 的病理过程，但 TLR4 在 CSVD 后血管性认知障碍（VCI）中的作用尚不清楚。
探讨 TLR4 在 VCI 发展中的作用及其机制。
监测雄性自发性高血压大鼠（SHR）和 Wistar Kyoto 大鼠（WKY）的血压（BP）。每 6 周使用 Morris 水迷宫（MWM）评估空间学习和记忆能力。每 12 周使用 3.0T 磁共振成像（MRI）评估大脑白质损伤。35 周后，所有大鼠断头取血，采用 Western blot 法检测海马 TLR4 的表达。采用免疫组化和免疫荧光法检测海马 TLR4、活性星形胶质细胞和小胶质细胞的阳性细胞数。
与 WKY 相比，SHR 的 BP 维持在较高水平，空间学习和记忆能力下降，IL-1β 和 TNF-α 水平升高。T2 加权 MRI 颅冠状扫描显示 SHR 胼胝体和外囊区高信号。此外，SHR 海马 TLR4、GFAP 和 Iba1 的表达增加。
高血压可导致小血管损伤和脑内部分白质变性。SHR 随年龄增长出现认知障碍，海马中 TLR4 高表达和胶质细胞反应是其发病机制之一。
