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.
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. The below-level gene expression profiles were compared with those of animals that were subjected to treadmill locomotor training.
Project description:The goal of this study is to elucidate the influence of treadmill training on transcriptome of the upper lumbar spinal cord after thoracic spinal cord hemisection. mRNA profiles of spinal cords at 23 days-post injury with/without treadmill training were generated. The expression levels of 650 genes in the trained animal were increased ( > 2-fold) compared to untrained animals. Our study represents the detailed analysis of transcriptomes of spinal cord distal to the hemisected lesion after treadmill training, with biologic replicates, generated by RNA-seq technology.
Project description:The goal of this study is to elucidate the influence of treadmill training on transcriptome of the lower lumbar spinal cord after thoracic spinal cord hemisection. mRNA profiles of spinal cords at 23 days-post injury with/without treadmill training were generated. The expression levels of 650 genes in the trained animal were increased ( > 2-fold) compared to untrained animals. Our study represents the detailed analysis of transcriptomes of spinal cord distal to the hemisected lesion after treadmill training, with biologic replicates, generated by RNA-seq technology.
Project description:Spinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI. The overall objective of this study is to implement genome wide expression profiling of skeletal muscle to define the molecular pathways associated with muscle remodeling after SCI and during locomotor training (TM). We profiled rat soleus of total 36 samples including controls; 3, 8 and 14 days after SCI; 8 and 14 days after SCI with locomotor treadmill training (TM).
Project description:Spinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI. The overall objective of this study is to implement genome wide expression profiling of skeletal muscle to define the molecular pathways associated with muscle remodeling after SCI and during locomotor training (TM).
Project description:The goal of this study is to elucidate the influence of hemisection injury at thoracic spinal cord (T9) on the transcriptome of the lower lumbar spinal cord at acute phase. mRNA profiles of spinal cord at 4 days-post injury and before injury were generated. 72 Differentially Expressed Genes (DEGs) were observed. Our study represents the detailed analysis of transcriptomes of spinal cord distal to the hemisected lesion at acute phase, with biologic replicates, generated by RNA-seq technology.
Project description:Male Sprague-Dawley rats were used to establish exhausted-exercise model by motorized rodent treadmill. Yu-Ping-Feng-San at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Quantitative proteomics was performed for assessing the related mechanism of Yu-Ping-Feng-San.
Project description:Membrane channels such as connexins (Cx), pannexins and P2X7 receptors are permeable to calcium, ATP and other small molecules. Release of ATP and glutamate through these channels is a key mechanism driving tissue response to traumas such as spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx hemichannels and pannexins. To test if boldine improved function after SCI, boldine or vehicle was administered to mice with a moderate severity contusion SCI. Boldine increased spared white matter and locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Increases in locomotor function observed after treadmill walking at a slow speed were further augmented by boldine. Boldine reduced immunostaining for activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked hemichannels, specifically Cx26 and Cx30, on cultured astrocytes and blocked calcium entry through activated P2X7R. Studies by RT-qPCR showed that boldine reduced expression of chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes SNAP25 and Grin2b, as well as GAP-43. Bulk RNA sequencing revealed that boldine modulated a large number of genes involved in neurotransmission in in spinal cord tissue just below the lesion epicenter at 14 days after SCI and that numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine spares tissue and increases locomotor function through mechanisms that may include reduced expression of pro-inflammatory molecules resulting in greater remodeling of surviving circuits