Transcriptomic Remodeling of the Spinal Cord-Injured Bladder and Its Modulation by Inosine Treatment
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PROVIDER: PRJNA1252057 | ENA |
REPOSITORIES: ENA
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Project description:Neurogenic detrusor overactivity (NDO) is a frequent complication of spinal cord injury (SCI), often accompanied by profound structural and functional changes in the bladder. While inosine has previously been shown to improve bladder function in SCI models, its molecular effects on the bladder remain largely unexplored. In this study, we performed transcriptomic profiling of bladder tissues from SCI rats treated with inosine or vehicle. Bladder compartments were microdissected into detrusor and mucosa to capture compartment-specific changes. SCI induced widespread transcriptional alterations in both compartments, with inosine treatment partially restoring gene expression patterns toward those observed in non-injured controls. Unsupervised clustering and principal component analyses confirmed distinct transcriptional profiles associated with injury and treatment. Notably, inosine influenced a set of genes consistently altered by SCI, suggesting a protective or regulatory role at the molecular level. These findings reveal a compartment-specific transcriptomic response to spinal cord injury and provide insight into the mechanisms by which inosine may exert its therapeutic effects on the injured bladder.
2025-07-09 | GSE294930 | GEO
Project description:This study investigates the molecular changes in the bladder following spinal cord injury (SCI) in rats and the impact of inosine treatment using a multi-omics approach. We discovered the activation of PARP (Poly(ADP-ribose) polymerase) in response to SCI, a previously unrecognized phenomenon, and its attenuation with inosine treatment. SCI triggered significant DNA damage and oxidative stress pathways, whereas inosine treatment prevents DNA damage and inhibits PARP activation, offering a potential therapeutic avenue. The integrated analysis of transcriptomics and proteomics data revealed concordant regulation of multiple pathways following SCI, including EIF2 signaling and NRF2-mediated oxidative stress response, which are ameliorated by inosine treatment. These findings have relevance to human neurogenic bladder pathobiology. Pathway inhibition by inosine in the setting of SCI suggests its potential for neuroprotection in the bladder. Despite limitations, such as the focus on male rats and a lack of proteomics data from separated detrusor and mucosa, this study provides valuable insights into the molecular mechanisms underlying bladder dysfunction following SCI. It also suggests the repurposing of FDA-approved PARP inhibitors for the treatment of bladder dysfunction following spinal injury.
2025-07-14 | PXD046096 | Pride
Project description:Spinal cord injury (SCI) evokes profound dysfunction in hollow organs such as the urinary bladder and gut. Current treatments are limited by a lack of molecular data to inform novel therapeutic avenues. Previously, we showed systemic treatment with the neuroprotective agent inosine improved bladder function following SCI in rats. This RNA-seq dataset captures global transcriptomic changes in the rat bladder at multiple time points following spinal cord injury (SCI). Full-thickness bladder tissues were collected from male Sprague Dawley rats at 2, 8, and 16 weeks post-complete T8 spinal cord transection, alongside non-injured controls.
2025-07-09 | GSE294927 | GEO
Project description:LncRNAs played a crucial role in the cell growth, development and some diseases relating to central nerve system.This study suggest that with regulating the LncRNAs expression level we might design novel therapy for spinalcord injury. In this dataset, we profiled the expression pattern of LncRNAs by microarray method after spinal cord injury (SCI). Through Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis seek LncRNAs potential function in the repair of spinal cord injury. Fifteen samples were analyzed. In these sample, we divided into five groups (sham operation, 1 day post-injured, 3 days post-injured, 1 week post-injued and 3 weeks post-injured) and each group contained three mice.After RNA extraction,RNA form mice in the same group were mixed by equal mass for the preparation of microarray.Compared with spinal cord without injury, the differential expression level of LncRNAs had a few changes at 1day post-injury, reached the peak at 1 week after SCI, and subsequently declined until 3 weeks post-injury. Genes with an FDR≤0.05 and a fold-change ≥2 were selected. Subsequently we analysis the significant differential expression genes.
2015-09-01 | E-GEOD-67515 | biostudies-arrayexpress
Project description:Purpose: The goal of this study was to determine the gene expression changes that occur over 7 days in parralyzed muscle in response to isometric contraction elicited by electrical stimulation initiated 4 months after spinal cord injury and to compare such changes to those observed in a normal muscle subjected to overload. Methods: Electrical stimulation of the soleus and plantaris muscle was stimulated in female rats with complete transection of the spinal cord at the interspace between the 9th and 10th thoracic vertebrae. Stimulation was begun 16 weeks after spinal cord transection and produced near-isometric contraction of soleus, plantaris and tibialis anterior. Muscle was analyzed at 1, 2 and 7 days after starting exercise with electrical stimulation. To provide a baseline reference for gene expression at 16 weeks after spinal cord injury, muscle was also analysed from an additional group of spinal cord transected animals. One additional group of animals with a sham-spinal cord injury was included to provide information about gene expression in neurologically intact animals of similar age. In parallel studies, rats underwent bilateral gastrocnemius ablation to overload soleus and plantaris, or a sham ablation as a control. Muscle was analyzed at 1, 3 and 7 days after gastrocnemius ablation or sham-ablation. Gene expression was determined using Affymetrix Rat Exon microarrays. For each group of animals, microarray analysis was performed for soleus muscle for each of 3 separate animals, using one array per animal. Control sammples for the spinal cord injured groups included a group of animals with a Sham-spinal cord injury, and a group of spinal cord injured animals that did not get electrical stimulation. The comparator for determining fold-change expression values was the spinal cord injured group that did not receive electrical stimulation. For each day after gastrocnemius ablation, a control was included that received all procedures needed for this ablation except cutting the distal insertion of the gastrocnemius into the Achilles tendon to control for effects of the surgery on gene expression.
2013-03-30 | E-GEOD-37476 | biostudies-arrayexpress
Project description:Human iPSC-derived thoracic spinal cord organoids were transplanted into spinal cord injury mice, and spinal cord tissue was collected after 7 weeks. The transplantation resulted in functional recovery and neural circuit remodeling in the injured mice.
2025-08-21 | GSE305911 | GEO
Project description:Previously, we demonstrated using a rat model of spinal cord injury (SCI) that bladder wall tissue compliance significantly increased within the first 2 weeks following injury. In order to explore the potential molecular-level mechanisms of this event, the present study quantified molecules pertinent to bladder tissue remodeling and changes in mechanical properties. An initial gene array analysis followed by real-time qPCR revealed that the message levels for tropoelastin and lysyl oxidase were as high as 8-fold in SCI rats compared to normal. Furthermore, both the message and protein levels of TGF-beta1 and IGF-1, known stimulators of elastin synthesis, in SCI rat bladders were significantly higher compared to those of normal rats. Taken together, it can be speculated that functional changes of the bladder associated with SCI induce release of select growth factors, which, in turn, stimulate elastogenesis that lead to alteration of biomechanical properties of the wall tissue.
2008-12-25 | GSE14096 | GEO
Project description:Mice lacking the developmental axon guidance molecule EphA4 have previously been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury, a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated or otherwise altered expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wild-type spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage / microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages / activated microglia in injured EphA4 knockout compared to wild-type spinal cords at two, four or fourteen days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages / activated microglia was observed in EphA4 knockout spinal cords at four days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury. Comparison was made between gene expression in wild-type and knockout samples both before and after injury. 3 replicates per group.
2012-05-23 | E-GEOD-34430 | biostudies-arrayexpress
Project description:Bladder Sensitivity to Inosine in Rat SCI: A Multi-Omics Study
| PRJEB67472 | ENA
Project description:Expression profiles of long non-coding RNAs in neurogenic bladder of spinal cord injured rats: A transcriptomic analysis
| PRJNA810864 | ENA