Department of Neurosurgery, Stanford University Medical Center, Stanford, CA, USA.
Department of Neurology, Stanford University Medical Center, Stanford, CA, USA.
Syst Rev. 2022 Apr 5;11(1):61. doi: 10.1186/s13643-022-01921-8.
Spinal cord injury (SCI) is a devastating condition with no current neurorestorative treatments. Clinical trials have been hampered by a lack of meaningful diagnostic and prognostic markers of injury severity and neurologic recovery. Objective biomarkers and novel therapies for SCI represent urgent unmet clinical needs. Biomarkers of SCI that objectively stratify the severity of cord damage could expand the depth and scope of clinical trials and represent targets for the development of novel therapies for acute SCI. MicroRNAs (miRNAs) represent promising candidates both as informative molecules of injury severity and recovery, and as therapeutic targets. miRNAs are small, regulatory RNA molecules that are tissue-specific and evolutionarily conserved across species. miRNAs have been shown to represent powerful predictors of pathology, particularly with respect to neurologic disorders.
Studies investigating miRNA alterations in all species of animal models and human studies of acute, traumatic SCI will be identified from PubMed, Embase, and Scopus. We aim to identify whether SCI is associated with a specific pattern of miRNA expression that is conserved across species, and whether SCI is associated with a tissue- or cell type-specific pattern of miRNA expression. The inclusion criteria for this study will include (1) studies published anytime, (2) including all species, and sexes with acute, traumatic SCI, (3) relating to the alteration of miRNA after SCI, using molecular-based detection platforms including qRT-PCR, microarray, and RNA-sequencing, (4) including statistically significant miRNA alterations in tissues, such as spinal cord, serum/plasma, and/or CSF, and (5) studies with a SHAM surgery group. Articles included in the review will have their titles, abstracts, and full texts reviewed by two independent authors. Random effects meta-regression will be performed, which allows for within-study and between-study variability, on the miRNA expression after SCI or SHAM surgery. We will analyze both the cumulative pooled dataset, as well as datasets stratified by species, tissue type, and timepoint to identify miRNA alterations that are specifically related to the injured spinal cord. We aim to identify SCI-related miRNA that are specifically altered both within a species, and those that are evolutionarily conserved across species, including humans. The analyses will provide a description of the evolutionarily conserved miRNA signature of the pathophysiological response to SCI.
Here, we present a protocol to perform a systematic review and meta-analysis to investigate the conserved inter- and intra-species miRNA changes that occur due to acute, traumatic SCI. This review seeks to serve as a valuable resource for the SCI community by establishing a rigorous and unbiased description of miRNA changes after SCI for the next generation of SCI biomarkers and therapeutic interventions.
The protocol for the systematic review and meta-analysis has been registered through PROSPERO: CRD42021222552 .
脊髓损伤 (SCI) 是一种毁灭性的疾病，目前尚无神经修复治疗方法。临床试验受到缺乏有意义的损伤严重程度和神经恢复的诊断和预后标志物的阻碍。SCI 的生物标志物和新疗法代表了迫切需要满足的临床需求。客观的脊髓损伤生物标志物可以对脊髓损伤的严重程度进行分层，从而扩大临床试验的深度和范围，并为急性 SCI 的新疗法的开发提供目标。微小 RNA（miRNA）作为损伤严重程度和恢复的信息分子，以及作为治疗靶点，具有很大的应用前景。miRNA 是一种小的、调节性的 RNA 分子，具有组织特异性和物种间的进化保守性。已经表明，miRNA 是病理的有力预测因子，特别是在神经疾病方面。
将从 PubMed、Embase 和 Scopus 中确定所有物种的动物模型和人类急性创伤性 SCI 研究中关于 miRNA 改变的研究。我们旨在确定 SCI 是否与跨物种保守的特定 miRNA 表达模式相关，以及 SCI 是否与组织或细胞类型特异性的 miRNA 表达模式相关。本研究的纳入标准包括：（1）发表于任何时间的研究；（2）包括所有物种和急性、创伤性 SCI 的性别；（3）涉及 SCI 后 miRNA 的改变，使用基于分子的检测平台，包括 qRT-PCR、微阵列和 RNA-seq；（4）包括脊髓、血清/血浆和/或 CSF 等组织中统计学上显著的 miRNA 改变；（5）具有假手术组的研究。综述中包含的文章将由两位独立作者对其标题、摘要和全文进行审查。将对 SCI 或假手术研究后的 miRNA 表达进行随机效应荟萃回归分析，该分析允许对研究内和研究间的变异性进行分析。我们将对累积的汇总数据集以及按物种、组织类型和时间点进行分层的数据集进行分析，以确定与受伤脊髓特别相关的 miRNA 改变。我们旨在确定在物种内特异性改变以及跨物种进化保守的与 SCI 相关的 miRNA，包括人类。分析将描述对 SCI 的病理生理反应的保守的种间和种内 miRNA 特征。
在这里，我们提出了一项系统评价和荟萃分析的方案，以研究由于急性、创伤性 SCI 而发生的保守的种间和种内 miRNA 变化。本综述旨在通过为下一代 SCI 生物标志物和治疗干预措施建立严格和无偏倚的 SCI 后 miRNA 变化描述，为 SCI 社区提供有价值的资源。
系统评价和荟萃分析的方案已通过 PROSPERO 注册：CRD42021222552。
