Project description:Biomarkers of spinal cord injury (SCI) could help determine the severity of the injury and facilitate early critical care decision making. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared to healthy and trauma controls and in direct relation to SCI severity. Unsupervised co-expression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS ‘A’) ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS ‘D’ SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.
Project description:Biomarkers to more accurately determine severity and prognosis following spinal cord injury (SCI) are needed to ensure that patients are assigned to the most suitable treatment and rehabilitation regimes. This study aimed to characterise the blood proteome following SCI in clinical rat injury models to identify novel candidate biomarkers and altered biological pathways.
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.
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.
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.
Project description:We investigated the gene expression profile of monocyte-derived macrophages and microglia following spinal cord injury. Moreover, we investigated the gene expression profole of M-CSF induced macrophages and new-born derived microglia following TGFb1 treatment. monocyte-derived macrophages and microglia following spinal cord injury M-CSF induced macrophages and new-born derived microglia following TGFb1 treatment
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.
Project description:To investigate the mechanism of electrical stimulation in the repair of spinal cord injury, we established a rat model of spinal cord injury. Then, we used RNA-SEQ data obtained from ES treatment and 6 different rat models of spinal cord injury for gene expression profile analysis.