Shin Samuel S, Gottschalk Amy C, Mazandi Vanessa M, Kilbaugh Todd J, Hefti Marco M
Department of Neurology, Hospital of University of Pennsylvania, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
College of Liberal Arts and Sciences, University of Iowa, Iowa City, Iowa, USA.
Neurotrauma Rep. 2022 Apr 19;3(1):178-184. doi: 10.1089/neur.2021.0051. eCollection 2022.
Transcriptomic investigations of traumatic brain injury (TBI) can give us deep insights into the pathological and compensatory processes post-injury. Thus far, transcriptomic studies in TBI have mostly used microarrays and have focused on rodent models. However, a large animal model of TBI bears a much stronger resemblance to human TBI with regard to the anatomical details, mechanics of injury, genetics, and, possibly, molecular response. Because of the advantages of a large animal TBI model, we investigated the gene expression changes between injured and uninjured sides of pig cerebral cortex after TBI. Given acute inflammation that follows after TBI and the important role that immune response plays in neuroplasticity and recovery, we hypothesized that transcriptional changes involving immune function will be upregulated. Eight female 4-week-old piglets were injured on the right hemisphere with controlled cortical impact (CCI). At 24 h after TBI, pericontusional cortex tissues from the injured side and contralateral cortical tissues were collected. After RNA extraction, library preparation and sequencing as well as gene expression changes between the ipsi- and contralateral sides were compared. There were 6642 genes that were differentially expressed between the ipsi- and contralateral sides, and 1993 genes among them had at least 3-fold differences. Differentially expressed genes were enriched for biological processes related to immune system activation, regulation of immune response, and leukocyte activation. Many of the differentially expressed genes, such as CD4, CD86, IL1A, IL23R, and IL1R1, were major regulators of immune function. This study demonstrated some of the major transcriptional changes between the pericontusional and contralateral tissue at an acute time point after TBI in pigs.
创伤性脑损伤（TBI）的转录组学研究能让我们深入了解损伤后的病理和代偿过程。到目前为止，TBI的转录组学研究大多使用微阵列，并聚焦于啮齿动物模型。然而，TBI的大型动物模型在解剖细节、损伤机制、遗传学以及可能的分子反应方面与人类TBI更为相似。由于大型动物TBI模型的优势，我们研究了TBI后猪大脑皮质损伤侧和未损伤侧之间的基因表达变化。鉴于TBI后会出现急性炎症，且免疫反应在神经可塑性和恢复中起重要作用，我们假设涉及免疫功能的转录变化将被上调。八只4周龄的雌性仔猪通过控制性皮质撞击（CCI）损伤右侧半球。TBI后24小时，收集损伤侧的挫伤周围皮质组织和对侧皮质组织。提取RNA、制备文库并进行测序，然后比较同侧和对侧之间的基因表达变化。同侧和对侧之间有6642个基因差异表达，其中1993个基因至少有3倍的差异。差异表达基因富集于与免疫系统激活、免疫反应调节和白细胞激活相关的生物学过程。许多差异表达基因，如CD4、CD86、IL1A、IL23R和IL1R1，是免疫功能的主要调节因子。这项研究展示了猪TBI后急性时间点挫伤周围组织和对侧组织之间的一些主要转录变化。
