Department of Neurosurgery, Tianjin Medical University General Hospital, China.
Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
J Cereb Blood Flow Metab. 2019 Dec;39(12):2497-2511. doi: 10.1177/0271678X18800593. Epub 2018 Sep 14.
Vascular dementia (VaD) affects cognition and memory. MicroRNA-126 (miR-126) is an angiogenic microRNA that regulates vascular function. In this study, we employ a multiple microinfarction (MMI) model to induce VaD in mice, and investigate VaD-induced cognitive dysfunction, white matter (WM) damage, glymphatic dysfunction and the role of miR-126 in mediating these effects. Male six-to eight-months old C57/BL6 mice (WT) were subject to MMI model, and cerebral blood flow (CBF), vessel patency, glymphatic function, cognitive function, and serum miR-126 expression were measured. Mice were sacrificed at 28 days after MMI. To investigate the role of miR-126 in VaD, cognitive function, water channel integrity and glymphatic function were assessed in male, six-to eight months old conditional-knockout endothelial cell miR-126 (miR-126), and control (miR-126) mice. MMI in WT mice induces significant cognitive deficits, decreases CBF and vessel patency; evokes astrocytic and microglial activation, increases inflammation, axonal/WM damage; decreases synaptic plasticity and dendritic spine density, instigates water channel and glymphatic dysfunction, and decreases serum miR-126 expression. MiR-126 mice exhibit significant cognitive impairment, decreased CBF, myelin density and axon density, increased inflammation, and significant water channel and glymphatic dysfunction compared to miR-126 mice. Reduction of endothelial miR-126 expression may mediate cognitive impairment in MMI-induced VaD.
血管性痴呆（VaD）影响认知和记忆。微小 RNA-126（miR-126）是一种血管生成微小 RNA，调节血管功能。在这项研究中，我们采用多发性微梗死（MMI）模型诱导小鼠 VaD，并研究 VaD 诱导的认知功能障碍、白质（WM）损伤、糖质渗透功能障碍以及 miR-126 在介导这些效应中的作用。雄性六至八个月大的 C57/BL6 小鼠（WT）接受 MMI 模型，测量脑血流（CBF）、血管通畅性、糖质渗透功能、认知功能和血清 miR-126 表达。MMI 后 28 天处死小鼠。为了研究 miR-126 在 VaD 中的作用，评估了雄性、六至八个月大的条件性内皮细胞 miR-126（miR-126）和对照（miR-126）小鼠的认知功能、水通道完整性和糖质渗透功能。WT 小鼠的 MMI 诱导明显的认知缺陷，降低 CBF 和血管通畅性；引发星形胶质细胞和小胶质细胞激活，增加炎症，轴突/WM 损伤；减少突触可塑性和树突棘密度，引发水通道和糖质渗透功能障碍，并降低血清 miR-126 表达。与 miR-126 小鼠相比，miR-126 小鼠表现出明显的认知障碍、降低的 CBF、髓鞘密度和轴突密度、增加的炎症以及明显的水通道和糖质渗透功能障碍。内皮细胞 miR-126 表达的减少可能介导 MMI 诱导的 VaD 中的认知障碍。
