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Comprehensive analysis of circRNA expression profiles in rat cerebral cortex after moderate traumatic brain injury.

ABSTRACT: Traumatic brain injury is a medical event of global concern, and a growing body of research suggests that circular RNAs can play very important roles in traumatic brain injury. To explore the functions of more novel and valuable circular RNA in traumatic brain injury response, a moderate traumatic brain injury in rats was established and comprehensive analysis of circular RNA expression profiles in rat cerebral cortex was done. As a result, 301 up-regulated and 284 down-regulated circular RNAs were obtained in moderate traumatic brain injury rats, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed based on the circular RNA's host genes, and a circRNA-miRNA interaction network based on differentially expressed circular RNAs was constructed. Also, four circular RNAs were validated by RT-qPCR and Sanger sequencing. This study showed that differentially expressed circular RNAs existed between rat cerebral cortex after moderate traumatic brain injury and control. And this will provide valuable information for circular RNA research in the field of traumatic brain injury.

SUBMITTER: Li G

PROVIDER: S-EPMC9108397 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Comprehensive analysis of circRNA expression profiles in rat cerebral cortex after moderate traumatic brain injury.

Li Gang G Li Shaoping S Liu Ruining R Yu Jiangtao J Ma Haoli H Zhao Yan Y

International journal of medical sciences 20220418 4

Traumatic brain injury is a medical event of global concern, and a growing body of research suggests that circular RNAs can play very important roles in traumatic brain injury. To explore the functions of more novel and valuable circular RNA in traumatic brain injury response, a moderate traumatic brain injury in rats was established and comprehensive analysis of circular RNA expression profiles in rat cerebral cortex was done. As a result, 301 up-regulated and 284 down-regulated circular RNAs w ...[more]

PMID: 35582420

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Project description:BackgroundTraumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent.ResultsAmong the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-delta and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, alpha-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen.ConclusionThe different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since trauma is a risk factor for development of neurodegenerative disease, this knowledge may also reduce late negative effects.

Project description:BackgroundHyperventilation-induced hypocapnia (HV) reduces elevated intracranial pressure (ICP), a dangerous and potentially fatal complication of traumatic brain injury (TBI). HV decreases the arteriolar diameter of intracranial vessels, raising the risk of cerebral ischemia. The aim of this study was to characterize the effects of moderate short-term HV in patients with severe TBI by using concomitant monitoring of cerebral metabolism, brain tissue oxygen tension (PbrO2), and cerebral hemodynamics with transcranial color-coded duplex sonography (TCCD).MethodsThis prospective trial was conducted between May 2014 and May 2017 in the surgical intensive care unit (ICU) at the University Hospital of Zurich. Patients with nonpenetrating TBI older than 18 years of age with a Glasgow Coma Scale (GCS) score < 9 at presentation and with ICP monitoring, PbrO2, and/or microdialysis (MD) probes during ICU admission within 36 h after injury were included in our study. Data collection and TCCD measurements were performed at baseline (A), at the beginning of moderate HV (C), after 50 min of moderate HV (D), and after return to baseline (E). Moderate HV was defined as arterial partial pressure of carbon dioxide 4-4.7 kPa. Repeated measures analysis of variance was used to compare variables at the different time points, followed by post hoc analysis with Bonferroni adjustment as appropriate.ResultsEleven patients (64% males, mean age 36 ± 14 years) with an initial median GCS score of 7 (IQR 3-8) were enrolled. During HV, ICP and mean flow velocity (CBFV) in the middle cerebral artery decreased significantly. Glucose, lactate, and pyruvate in the brain extracellular fluid did not change significantly, whereas PbrO2 showed a statistically significant reduction but remained within the normal range.ConclusionModerate short-term hyperventilation has a potent effect on the cerebral blood flow, as shown by TCCD, with a concomitant ICP reduction. Under the specific conditions of this study, this degree of hyperventilation did not induce pathological alterations of brain metabolites and oxygenation.Trial registrationNCT03822026 . Registered on 30 January 2019.

Dataset Information

Comprehensive analysis of circRNA expression profiles in rat cerebral cortex after moderate traumatic brain injury.

Publications

Comprehensive analysis of circRNA expression profiles in rat cerebral cortex after moderate traumatic brain injury.

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