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Hyperbaric oxygen therapy after mid-cervical spinal contusion injury

ABSTRACT: Hyperbaric oxygen (HBO) therapy is frequently used to treat peripheral wounds or decompression sickness. Evidence suggests that HBO therapy can provide neuroprotection and has an anti-inflammatory impact after neurologic injury including spinal cord injury (SCI). Our primary purpose was to conduct an unbiased, genome-wide screening of mRNA expression changes in the injured spinal cord after HBO therapy. A mRNA gene array was used to evaluate samples taken from the contused region of the spinal cord following a lateralized mid-cervical contusion injury in adult female rats. HBO therapy consisted of daily, 1-hour sessions (3.0 ATA, 100% O2) initiated on the day of SCI. Gene set enrichment analyses indicated that HBO upregulated genes in pathways associated with electron transport, mitochondrial function, and oxidative phosphorylation, and downregulation genes in pathways associated with inflammation (including cytokines and NF-B) and apoptotic signaling. In a separate cohort, spinal cord histology was performed to verify whether the HBO treatment impacted neuronal cell counts or inflammatory markers. Compared to untreated rats, there was increased NeuN positive cells in the spinal cord of HBO treated rats (p=0.007). Further, staining for anti-ionized calcium binding adaptor protein (Iba-1, a microglial marker) was reduced after HBO (p=0.028). We conclude that HBO therapy, initiated shortly after SCI and continued for 10-days, can alter the molecular signature of the lesioned spinal cord in a manner consistent with an anti-inflammatory and neuroprotective impact.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE185600 | GEO | 2022/05/18

REPOSITORIES: GEO

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Analysis of long noncoding RNAs expression profiles explores mechanisms of hyperbaric oxygen treatment promoting spinal cord injury recovery

Project description:Aims: To better understand the potential mechanisms of hyperbaric oxygen (HBO) treatment alleviating spinal cord injury (SCI). Materials and methods: The SCI model was firstly built in mice, which were randomly divided into three groups: Sham (SH), SCI and HBO groups, followed by hind limb motor function evaluation. Then the spinal cord tissue samples were harvested for genome-wide transcriptional analysis at 1 week after injury. Finally, some highly expressed lnc-rna were selected for functional analysis. Results: the present study uncovered the lncRNAs expression profile of spinal cord following HBO treatment, and identified 577 DE lncRNAs in spinal cord sample among the SH, SCI and HBO groups. The key biological process and pathways were also identified and may be important mechanisms by which HBO treatment alleviating SCI Conclusions: Moreover, this study indicated that lncRNAs NONMMUT 092674.1 and NONMMUT042986.2 may be involved in the process of HBO treatment promoting the recovery of neurological function after SCI.

2022-03-24 | GSE199043 | GEO

Next Generation Sequencing facilitates quantitative analysis of spinal cord tissue to explore the mechanisms of hyperbaric oxygen treatment alleviating the spinal cord inury

Project description:Aims: To better understand the potential mechanisms of hyperbaric oxygen (HBO) treatment alleviating spinal cord injury (SCI). Materials and methods: The SCI model was firstly built in mice, which were randomly divided into three groups: Sham (SH), SCI and HBO groups, followed by hind limb motor function evaluation. Then the spinal cord tissue samples were harvested for histological evaluation and genome-wide transcriptional analysis at 1 week after injury. Finally, some oxidative stress and cell death related differently expressed genes were selected to be analyzed followed by the functional analysis. Results: HBO treatment significantly improved the recovery of hind limb motor function and decreased the histology score compared to the SCI group. In the genome-wide transcriptional analysis, a total of 76 common differently expressed gene among the three groups were obtained at 1 week after injury, which were enriched in functional pathway such as ferroptosis, calcium signaling pathway, serotonergic synapse, etc. Trends in expression of the six genes were consistent with transcriptional analysis. Conclusions: Identified differentially expressed genes and related signaling pathways may be associated with HBO treatment alleviating second spinal cord injury. These results contribute to elucidate the mechanism of HBO in the treatment of SCI.

2021-10-08 | GSE185301 | GEO

Transcription profiling time series analyzing the molecular events in rat spinal cord sections following mechanical injury

Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Hypothesis: Spinal cord injury (SCI) induces a cascade of molecular events including the activation of genes associated with transcription factors, inflammation, oxidative stress, ionic imbalance, apoptosis and neuroregeneration which suggests the existance of endogenous reparative attempts. However, not all mechanisms following SCI are well known. Specific Aim: The goal of this project is to analyze the molecular events following spinal cord injury 1 cm above, below, and at the site of injury (T9), aiming at finding potential new targets to improve recovery and therapy.

2007-09-04 | E-GEOD-464 | biostudies-arrayexpress

Small Extracellular Vesicles derived from four dimensional-culture of mesenchymal stem cells induce alternatively activated macrophages by upregulating IGFBP2/EGFR to attenuate inflammation in the spinal cord injury of rats

Project description:Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the “4D-sEVs”). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.

2023-07-20 | PXD040516 | Pride

The initiating IL-10 production dominates the therapy of mesenchymal stem cell scaffold in spinal cord injury

Project description:spinal cord injury (SCI) is an acute damage to central nevous system, resulting in severe morbidity and permanent disability. Locally implanting scaffold system immobilized mesenchymal stem cellshas been widely proven to promote the locomotor function recovery of SCI rat, but the underlying mechanism remains elusive. Here we constructed a hyaluronic acid scaffold system (HA-MSC) to accelerates human MSC adhesive growth and prolongs the survival time of MSC in the lesion of SCI rats. And the residual MSCs regulate the local immune responses by upregulating anti-inflammatory cytokines. Interestingly, the dramatically increased but transient expression of IL-10 is found secreted by MSCs in the first week. Blocking the function of the initiating produced IL-10 by antibody totally abolishes the neurological and behavioral recovery of SCI rats, indicating a core role of IL-10 in SCI therapy of HA-MSC implantation. Transcriptome analyses indicate that IL-10 selectively promotes the migration and cytokine secretion programs of MSC, which in turn help MSC to exert its anti-inflammatory therapeutic effects. Our findings thus highlight a novel role of IL-10 in regulating MSC migration and cytokine secretion and determine the vital role of IL-10 in the domination of MSC treatment for spinal cord repair.

2024-01-16 | GSE240755 | GEO

Circular RNA expression alteration in rats after traumatic spinal cord injury (SCI)

Project description:To determine whether the expression levels of circular RNAs were altered and lay a foundation for future work, we used high-throughput microarray analysis to screen circular RNAs expression patterns in the spinal cord of adult rats after traumatic spinal cord injury (SCI), finally to evaluate the potential rat models as a platform for the development of novel therapeutic targets for spinal cord injury in future clinical studies. Overall six rats at 3 days post-SCI in two groups were used to perform the microarray.

2018-05-15 | GSE114426 | GEO

CNS Regeneration

Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or desease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Hypothesis: Spinal cord injury (SCI) induces a cascade of molecular events including the activation of genes associated with transcription factors, inflammation, oxidative stress, ionic imbalance, apoptosis and neuroregeneration which suggests the existance of endogenous reparative attempts. However, not all mechanisms following SCI are well known. Specific Aim: The goal of this project is to analyze the molecular events following spinal cord injury 1 cm above, below, and at the site of injury (T9), aiming at finding potential new targets to improve recovery and therapy. Keywords: other

2003-07-16 | GSE464 | GEO

Gene expression profiles in the spinal cord below the lesion level and influence of treadmill locomotor training

Project description:Traumatic spinal cord injury (SCI) often leads to loss of locomotor function. Neuroplasticity of spinal circuitry underlies some functional recovery and therefore represents a therapeutic target to improve locomotor function following SCI. However, the cellular and molecular mechanisms mediating neuroplasticity below the lesion level are not fully understood. The present study performed a gene expression profiling in the rat lumbar spinal cord at 1 and 3 weeks after contusive SCI at T9 compared to control rat that received sham injury (laminectomy). The below-level gene expression profiles were compared with those of animals that were subjected to treadmill locomotor training. Rat lumbar spinal cords were taken for the microarray analysis at 1 and 3 weeks after contusive spinal cord injury at the T9 level. Another group of rats received treadmill locomotor training for 3 weeks, and theirs spinal cords were harvested for the microarray. The changes in gene expression after spinal cord injury were analyzed at the two time points. The influence of treadmill locomotor training was evaluated by comparing gene expression profiles between animals with or without treadmill training.

2013-11-27 | E-GEOD-52763 | biostudies-arrayexpress

Transcription profiling time series of Rattus norvegicus raphe magnus and sensorimotor cortex samples following moderate spinal cord injury

Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9.

2007-10-08 | E-GEOD-2270 | biostudies-arrayexpress

Administration of tamoxifen regulates changes in gene expression during the acute phase of traumatic spinal cord injury

Project description:Traumatic spinal cord injury (SCI) may induce irreversible damage leading to severe incapacity. Molecular mechanisms underlying SCI are not fully understood, preventing the development of novel therapeutic resources. Tamoxifen has demonstrated to be a promising therapy. Our aim was to elucidate the molecular mechanisms involved in the beneficial effect of TMX administered after SCI. We use a rat model of SCI, Tamoxifen was administred intraperitoneal 30 min after injury. Four groups were organized, 1) Non-injured without TMX (Sham/TMX-), 2) Non-injured with TMX (Sham/TMX+), 3) Injured without TMX (SCI/TMX-), and 4) Injured with TMX (SCI/TMX+). From the comparison between Sham/TMX- and SCI/TMX-, 708 genes showed differential expression. Among the relevant genes Anxa1 was upregulated, this gene’s product is a promising marker of injury severity. Enriched pathways were the spinal cord injury pathway and pathways related to inflammatory response. When comparing SCI/TMX- versus SCI/TMX+, only 30 genes showed differential expression. Our results reinforce the key role of inflammatory response in SCI and Tamoxifen seem to be able to regulate this response by suppressing changes in gene expression. Our data also support the potential of previously described severity markers.

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