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Transcriptional changes in soleus muscle for rats exposed to different activities after contusion injury to the spinal cord and transcriptional changes in soleus muscle with complete spinal cord transection injury

ABSTRACT: Spinal cord injury (SCI) is a devastating clinical condition resulting in significant disabilities for affected individuals. Apart from local injury within the spinal cord, SCI patients develop a myriad of complications characterized by multi-organ dysfunction. Disorders, such as lung injury, cardiovascular disease, liver damage, kidney and urinary tract dysfunction, alterations in gut microbiome, neuropathic pain, depression and altered immune responses are common in SCI patients. Such whole body, systemic responses hinder the functional recovery and can be life-threatening in SCI population. Investigations of organ specific gene expression analyses can provide a better understanding of the injury response and identify molecular targets. Consequently, this can be used to develop treatment for SCI, promoting functional recovery and overall quality of life.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE129694 | GEO | 2020/04/07

REPOSITORIES: GEO

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Integrated systems analysis reveals conserved gene networks underlying response to spinal cord injury

Project description:Spinal cord injury (SCI) is a devastating neurological condition for which there are currently no effective treatment options to restore function. A major obstacle to the development of new therapies is our fragmentary understanding of the coordinated pathophysiological processeses triggered by damage to the human spinal cord. An additional challenge to translation of preclinical therapies is the reliance of clinical trials on standardized neurological assessments to enrol and stratify patients, rather than objective injury biomarkers. Here, we describe a systems biology approach to integrate decades of small-scale experiments with unbiased, genome-wide gene expression from the human spinal cord, revealing a gene regulatory network signature of the pathophysiological response to SCI. Our integrative analyses converge on an evolutionarily conserved gene subnetwork enriched for genes associated with the response to SCI by small-scale experiments, and whose expression is upregulated in a severity-dependent manner following injury and downregulated in functional recovery. We validate the severity-dependent upregulation of this subnetwork in prospective transcriptomic and proteomic studies. Our analysis provides a systems-level view of the coordinated molecular processes activated in response to SCI. Further, our results nominate quantitative biomarkers of injury severity and functional recovery, with the potential to facilitate development and translation of novel therapies.

2018-09-25 | PXD010192 | Pride

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

Chronic contusion spinal cord injury in rats

Project description:Excerpt from a larger study which characterized the transcriptional effects of a spinal cord contusion injury in rats. This is the data from the almost chronic contusion state (35 days) at the injury site (Thoracic 8) - where we saw significant changes in several areas, including cholesterol metabolism genes. Other spinal cord areas (rostral, caudal) and time-points (3 hours, 24 hours, 7 days and 35 days) were analyzed as well and are discussed in our paper and at www.crpf.org/microarray. Keywords = Spinal Cord Injury Keywords = chronic Keywords = thoracic Keywords = cholesterol Keywords: repeat sample

2005-05-03 | GSE2599 | GEO

Activity-induced changes in the liver transcriptome after chronic spinal cord injury

Project description:Spinal cord injury (SCI) is a devastating clinical condition resulting in significant disabilities for affected individuals. Apart from local injury within the spinal cord, SCI patients develop a myriad of complications characterized by multi-organ dysfunction. Disorders, such as lung injury, cardiovascular disease, liver damage, kidney and urinary tract dysfunction, alterations in gut microbiome, neuropathic pain, depression and altered immune responses are common in SCI patients. Such whole body, systemic responses hinder the functional recovery and can be life-threatening in SCI population. Investigations of organ specific gene expression analyses can provide a better understanding of the injury response and identify molecular targets. Consequently, this can be used to develop treatment for SCI, promoting functional recovery and overall quality of life.

2019-04-29 | GSE124819 | GEO

Danio spinal cord injury

Project description:Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, which shows that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene, Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis after spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals. Spinal cord injury or control sham injury was performed on adult zebrafish. After 4, 12, or 264 hrs, a 5 mm segment of spinal cord was dissected and processed (as a pool from 5 animals) in three replicate groups for each time point and treatment.

2010-10-19 | E-GEOD-20460 | biostudies-arrayexpress

Human spinal cord injury plasma LC-MSMS

Project description:The primary aim of this work was to investigage the proteomic differences across spinal cord injury (SCI) patients who experience significant functional recovery relative to those who do not, to both better understand the pathophysiology and to identify potentially useful biomarkers of recovery. Blood samples were taken, following informed consent, from ASIA impairment scale (AIS) grade C "Improvers" (AIS grade improvement) (n=10 & n=9) and "Non-Improvers" (No AIS change) (n=7 & n=6), and AIS grade A (n=11 & n= 9) and D (n=11 & n=10) at <2 weeks ("Acute") and approx. 3 months ("Sub-acute") post-injury for a total of 73 samples. The samples were treated with ProteoMiner™ beads. Data dependent label-free LC-MSMS was used to characterise the proteome of the samples.

2022-07-14 | PXD035072 | Pride

Genome-Wide Gene Expression Profiling of Spinal Cord Injury in Rat

Project description:The aneurysm clip impact-compression model of spinal cord injury (SCI) in animals mimics the primary mechanism of SCI in human, i.e. acute impact and persisting compression; and its histo-pathological and behavioural outcomes are extensively similar to the human SCI. In order to understand the distinct molecular events underlying this injury model, an analysis of global gene expression of the acute, subacute and chronic stages of a moderate to severe injury to the rat spinal cord was conducted using a microarray gene chip approach. Rat thoracic spinal cord (T7) was injured using aneurysm clip impact-compression injury model and the epicenter area of injured spinal cord was isolated for RNA extraction and processing and hybridization on Affymetrix GeneChip arrays.

2013-11-15 | E-GEOD-45006 | biostudies-arrayexpress

Patterns of gene Expression during the Spinal cord Injury/Regeneration

Project description:Spinal cord injury (SCI) induces a sequence of endogenous autodestructive changes known as secondary injury, as well as reactive biochemical changes that are neuroprotective and/or promote recovery. All these responses to SCI are, in part reﬂected in changes in gene expression. In order to assess changes in gene expression involved in the regeneration process,microarrays were performed as a function of time after SCI for the various treatments.

2012-01-01 | GSE29488 | GEO

Hyperbaric oxygen therapy after mid-cervical spinal contusion injury

Project description: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.

2022-05-18 | GSE185600 | GEO

RNA-Seq analysis after spinal cord injury in lamprey reveals distinct transcriptional responses during functional recovery in spinal cord and brain

Project description:The lamprey is a vertebrate that, unlike mammals, achieves spontaneous recovery after spinal cord transection. Despite anatomical, physiological, and behavioral data on spinal cord regeneration in lamprey, the molecular mechanisms underlying this capacity are largely unknown. To address this, we used RNA-Seq to obtain transcriptional profiles from uninjured animals and at 10 time points ranging from 6 hours to 12 weeks post injury. Overall, 4208 (spinal cord) and 3788 (brain) transcripts are differentially expressed (DE). Complex intraspinal and supraspinal responses were induced acutely and occurred even at chronic phases of recovery. Leveraging functional data for mammalian homologs of DE genes (via Enrichr) permitted identification of enriched conserved genes and pathways. These included genes and pathways induced after mammalian peripheral nerve injury, such as those associated with regeneration, immune function, cell growth, proliferation and cell death. For example, ATF3, a transcription factor implicated in mammalian peripheral nerve regeneration, is highly expressed and enriched in lamprey spinal cord and brain after SCI. Other homologs of regeneration-associated genes that are differentially expressed after SCI include members of the WNT, HDAC, SOX, SMAD, KLF, and JUN families. This study provides the first comprehensive view of transcriptional responses during successful anatomical and functional recovery from spinal cord injury in lamprey, and reveals unexpectedly large changes in transcription in the brain, which is quite distant from the spinal lesion site. Gene expression patterns associated with functional recovery in lamprey may be useful in guiding studies aimed at modulating mammalian responses to SCI.

2018-03-03 | GSE95686 | GEO

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