Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, S514 BST, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, 15261, USA.
Fluids Barriers CNS. 2022 Mar 26;19(1):27. doi: 10.1186/s12987-022-00317-z.
The blood-brain barrier (BBB) is an essential component of the neurovascular unit that controls the exchanges of various biological substances between the blood and the brain. BBB damage is a common feature of different central nervous systems (CNS) disorders and plays a vital role in the pathogenesis of the diseases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs), are important regulatory RNA molecules that are involved in almost all cellular processes in normal development and various diseases, including CNS diseases. Cumulative evidences have demonstrated ncRNA regulation of BBB functions in different CNS diseases. In this review, we have summarized the miRNAs, lncRNAs, and circRNAs that can be served as diagnostic and prognostic biomarkers for BBB injuries, and demonstrated the involvement and underlying mechanisms of ncRNAs in modulating BBB structure and function in various CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), spinal cord injury (SCI), multiple sclerosis (MS), Alzheimer's disease (AD), vascular cognitive impairment and dementia (VCID), brain tumors, brain infections, diabetes, sepsis-associated encephalopathy (SAE), and others. We have also discussed the pharmaceutical drugs that can regulate BBB functions via ncRNAs-related signaling cascades in CNS disorders, along with the challenges, perspective, and therapeutic potential of ncRNA regulation of BBB functions in CNS diseases.
血脑屏障（BBB）是神经血管单元的重要组成部分，控制着血液和大脑之间各种生物物质的交换。BBB 损伤是不同中枢神经系统（CNS）疾病的共同特征，在疾病的发病机制中起着至关重要的作用。非编码 RNA（ncRNA），如 microRNAs（miRNAs）、长非编码 RNA（lncRNAs）和环状 RNA（circRNAs），是参与正常发育和各种疾病（包括中枢神经系统疾病）中几乎所有细胞过程的重要调节 RNA 分子。越来越多的证据表明，ncRNA 调节不同中枢神经系统疾病中的 BBB 功能。在这篇综述中，我们总结了可作为 BBB 损伤诊断和预后生物标志物的 miRNAs、lncRNAs 和 circRNAs，并展示了 ncRNA 参与调节各种中枢神经系统疾病中 BBB 结构和功能的机制，包括缺血性中风、出血性中风、创伤性脑损伤（TBI）、脊髓损伤（SCI）、多发性硬化症（MS）、阿尔茨海默病（AD）、血管性认知障碍和痴呆（VCID）、脑肿瘤、脑感染、糖尿病、脓毒症相关脑病（SAE）等。我们还讨论了可通过中枢神经系统疾病中 ncRNA 相关信号级联调节 BBB 功能的药物，以及 ncRNA 调节中枢神经系统疾病中 BBB 功能的挑战、前景和治疗潜力。
