1 Department of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
2 Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA, USA.
J Cereb Blood Flow Metab. 2018 Jul;38(7):1125-1148. doi: 10.1177/0271678X18773871. Epub 2018 Apr 30.
Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.
中枢神经系统（CNS）损伤，如中风、创伤性脑损伤（TBI）和脊髓损伤（SCI），是全球范围内重要的死亡和长期残疾原因。微小 RNA（miRNA）是一种负调控基因表达的小非编码 RNA 分子，可作为诊断生物标志物，并成为 CNS 损伤的新型治疗靶点。基于 miRNA 的治疗方法包括 miRNA 模拟物和抑制剂（antagomiRs），分别降低和增加靶基因的表达。在这篇综述中，我们总结了目前在中风、TBI 和 SCI 中基于 miRNA 的治疗应用。讨论了 miRNA 药物有效递送至 CNS 的给药方法、时间窗和剂量。还回顾了基于 miRNA 的治疗的潜在机制，包括氧化应激、炎症、细胞凋亡、血脑屏障保护、血管生成和神经发生。还介绍了通过针对特定 miRNAs 来保护 CNS 损伤的药理学药物，以及 miRNA 治疗的挑战和治疗潜力。
