Boldine increases functional recovery and response to physical rehabilitation in a mouse model of contusion spinal cord injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA911838 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22721167_1.fastq.gz | Fastqsanger.gz | |||
| SRR22721167_2.fastq.gz | Fastqsanger.gz | |||
| SRR22721168_1.fastq.gz | Fastqsanger.gz | |||
| SRR22721168_2.fastq.gz | Fastqsanger.gz | |||
| SRR22721169_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
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
2023-07-12 | GSE220907 | GEO
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
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.
2007-10-08 | E-GEOD-2599 | biostudies-arrayexpress
Project description:Axons fail to regenerate in the injured spinal cord, limiting motor and autonomic recovery and contributing to long-term morbidity. Endogenous inhibitors, including those on residual myelin, contribute to regeneration failure. One inhibitor, myelin-associated glycoprotein (MAG), binds to sialoglycans and other receptors on axons. MAG inhibition of axon outgrowth in some neurons is reversed by treatment with sialidase, an enzyme that hydrolyzes sialic acids and eliminates MAG-sialoglycan binding. We delivered recombinant sialidase intrathecally to rats following a spinal cord contusive injury. Sialidase (or saline solution) was infused to the injury site continuously for 2 wk and then motor behavior, autonomic physiology, and anatomic outcomes were determined 3 wk later. Sialidase treatment significantly enhanced hindlimb motor function, improved bulbospinally mediated autonomic reflexes, and increased axon sprouting. These findings validate sialoglycans as therapeutic targets and sialidase as a candidate therapy for spinal cord injury.
| S-EPMC2895144 | biostudies-other
Project description:Several interventions promote axonal growth and functional recovery when initiated shortly after central nervous system injury, including blockade of myelin-derived inhibitors with soluble Nogo receptor (NgR1, RTN4R) decoy protein. We examined the efficacy of this intervention in the much more prevalent and refractory condition of chronic spinal cord injury.We eliminated the NgR1 pathway genetically in mice by conditional gene targeting starting 8 weeks after spinal hemisection injury and monitored locomotion in the open field and by video kinematics over the ensuing 4 months. In a separate pharmacological experiment, intrathecal NgR1 decoy protein administration was initiated 3 months after spinal cord contusion injury. Locomotion and raphespinal axon growth were assessed during 3 months of treatment between 4 and 6 months after contusion injury.Conditional deletion of NgR1 in the chronic state results in gradual improvement of motor function accompanied by increased density of raphespinal axons in the caudal spinal cord. In chronic rat spinal contusion, NgR1 decoy treatment from 4 to 6 months after injury results in 29% (10 of 35) of rats recovering weight-bearing status compared to 0% (0 of 29) of control rats (p < 0.05). Open field Basso, Beattie, and Bresnahan locomotor scores showed a significant improvement in the NgR-treated group relative to the control group (p < 0.005, repeated measures analysis of variance). An increase in raphespinal axon density caudal to the injury is detected in NgR1 decoy-treated animals by immunohistology and by positron emission tomography using a serotonin reuptake ligand.Antagonizing myelin-derived inhibitors signaling with NgR1 decoy augments recovery from chronic spinal cord injury.
| S-EPMC3238798 | biostudies-literature
Project description:Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p < 0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.
| S-EPMC5908429 | biostudies-literature
Project description:Identification of temporal variations in miRNA expression after spinal cord injury caused by thoracic (T8) moderate (200 Kdynes) contusion. Expression changes were analyzed 1, 3 and 7 days after injury and compared to expression of control (untreated) and sham (laminectony but no contusion) individuals.
2011-07-01 | GSE19890 | GEO
Project description:Membrane channels such as those formed by connexins (Cx) and P2X7 receptors (P2X7R) are permeable to calcium ions and other small molecules such as adenosine triphosphate (ATP) and glutamate. 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 and Panx1 hemichannels (HCs). To test if boldine could improve function after SCI, boldine or vehicle was administered to treat mice with a moderate severity contusion-induced SCI. Boldine led to greater spared white matter and increased locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Boldine treatment reduced immunostaining for markers of activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked glial HC, specifically Cx26 and Cx30, in cultured astrocytes and blocked calcium entry through activated P2X7R. RT-qPCR studies showed that boldine treatment reduced expression of the chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes Snap25 and Grin2b, and Gap-43. Bulk RNA sequencing revealed that boldine modulated a large number of genes involved in neurotransmission in spinal cord tissue just caudal from the lesion epicenter at 14 days after SCI. Numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine treatment ameliorates injury and spares tissue to increase locomotor function.
| S-EPMC10321410 | biostudies-literature
Project description:The purpose of the study is to understand the role of Bmal1 in spinal cord contusion.
2023-06-01 | GSE151685 | GEO
Project description:Identification of temporal variations in miRNA expression after spinal cord injury caused by thoracic (T8) moderate (200 Kdynes) contusion. Expression changes were analyzed 1, 3 and 7 days after injury and compared to expression of control (untreated) and sham (laminectony but no contusion) individuals. Included groups: control (untreated), 1 day after lesion, 3 days after lesion, 7 days after lesion, 1 days after SHAM cirugy, 3 days after SHAM cirugy, and 7 days after SHAM cirugy. Each of these 7 groups included 5 biological replicates.
2011-07-01 | E-GEOD-19890 | biostudies-arrayexpress