Boldine increases functional recovery and response to physical rehabilitation in a mouse model of contusion spinal cord injury
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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 |
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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: Not available
| S-EPMC10321410 | biostudies-literature
Project description:Spinal cord injury (SCI) frequently leads to permanent motor and sensory deficits, with complete injuries causing total loss of function below the lesion and incomplete injuries preserving only partial connectivity. Intracortical delivery of an AAV2 vector encoding the designer cytokine hyper-interleukin-6 (AAV2-hIL-6) enhances recovery after complete SCI by transneuronally stimulating raphe nuclei. Here, we verified that AAV2-hIL-6 transneuronally activates subcortical neurons in the medulla and evaluated that this strategy enables recovery in clinically more relevant mouse models of mild, moderate, and severe contusion injury. Across all severities, AAV2-hIL-6 treatment significantly improved locomotor function compared to AAV2-GFP-treated controls. Although lesion size and neuronal loss correlated with contusion severity and were unaffected by the AAV2-hIL-6 treatment, it robustly increased the number and length of descending serotonergic axons in the lumbar cord. Selective ablation of serotonergic neurons abolished these gains, confirming their essential role in functional sensorimotor recovery. However, while AAV2-hIL-6 also reduced corticospinal tract (CST) axon retraction, it did not induce axon regeneration beyond the lesion, suggesting that CST regeneration was not required for recovery. Thus, intracortical AAV2-hIL-6 delivery drives circuit remodeling and functional restoration across contusion severities, highlighting its promise as a regenerative therapy for SCI with spared pathways.
2026-04-22 | GSE327851 | GEO
Project description:Background: Neuropathic pain is a complex, chronic condition affecting 7% to 10% of the general population. Current neuropathic pain treatments fail to provide adequate relief in at least ~40% of patients and are usually accompanied by side effects that are sometimes severe. In this study, we investigated the effect of boldine, a natural occurring alkaloid, in attenuating peripheral nerve injury-induced neuropathic pain symptoms and transcriptomic changes. Methods: Male C57BL6 mice were subjected to chronic constriction injury (CCI) to the sciatic nerve. Customized chow containing boldine or control chow was administered right after surgery. Mechanical pain responses were assessed by Von Frey filament test. Spontaneous pain-like weight bearing behavior was measured using the dynamic weight bearing system. Spinal cords were collected at 15 days post injury and subjected to quantitative PCR and bulk RNA sequencing. Results: CCI led to ipsilateral hypersensitivity of mechanical pain responses and weight bearing deficits including reduced rearing duration, ipsilateral/contralateral weight support ratio, and ipsilateral hind paw posed duration. Boldine treatment substantially attenuated CCI-induced mechanical allodynia, but not the weight bearing deficits. Gene expression analysis showed that boldine inhibited CCI-induced upregulation of inflammatory markers in the spinal cord. RNA sequencing analysis revealed several pain-related canonical pathways and upstream factors after CCI, and boldine treatment markedly reversed these CCI-induced transcriptomic changes. Conclusions: In a mouse model of CCI, oral administration of boldine reduced nerve injury-induced mechanical allodynia and counter-regulated injury-associated transcriptomic changes in the spinal cord, possibly through regulating inflammation and immune responses.
2026-08-26 | GSE344718 | GEO
Project description:Gene expression analysis after the treatments for functional recovery after contusion injury which are mediated by glutathione Experiment Overall Design: 24 hours after contusion and treatments Experiment Overall Design: Groups include normal, laminectomy, contusion and treatments on contused rats (clenbuterol, X-ray, tempol, BSO and tempol/BSO)
2008-06-13 | E-GEOD-5273 | biostudies-arrayexpress
Project description:Developing molecular methods for assessing the effectiveness of physical rehabilitation remains a pressing task. Our study aimed to assess the utility of transcriptome analysis of muscle biopsies in evaluating the efficacy of the isometric exercises (IE) added to the standard protocol in early rehabilitation of older patients during the initial two weeks post total hip arthroplasty (THA). Blood concentrations of total leukocytes, neutrophils, IL6, IL8, IL1β, myoglobin, etc. were measured, and transcriptome analysis of rectus femoris biopsies from the operated leg was performed before and after (1 and 12 days) THA in women aged 73–77 years. The additional IE in the experimental rehabilitation group led to a significant acceleration in the recovery of IL6, IL8 and IL1β blood levels to the normal ranges compared to the control group, as confirmed by Fisher’s exact test for this cytokine combination. The results of Gene Set Enrichment Analysis and Differen-tially Expressed Gene Analyses for the muscle biopsies point to accelerated resolution of inflammation, along with enhanced activation of genes associated with angiogenesis, lymphangiogenesis, vasodilation, and vasoconstriction in the experimental rehabilita-tion group compared to the control group. Thus, IL6, IL8 and IL1β blood levels can serve being in combination as molecular indicators of the efficacy of early rehabilitation after THA, and transcriptome analysis of the rectus femoris biopsies of the operated leg allows revealing molecular indicators of regenerative processes in muscle tissue near the surgery area after THA.
2026-02-18 | GSE315228 | GEO
Project description:Many Veterans who experienced blast-related traumatic brain injuries (TBI) during their military service suffer from chronic cognitive and mental health problems including post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast injuries designed to mimic the type of blast-related mild TBI that was so common in the conflicts in Iraq and Afghanistan conflicts develop delayed and persistent cognitive and PTSD-related traits that remain present for over one year after exposure. Boldine, an alkaloid derived from the Chilean Boldo tree (Peumus boldus), is widely used herbal remedy with anti-oxidant, anti-inflammatory, hepatoprotective, and connexin hemichannel-blocking properties. We studied whether oral administration of boldine could prevent development of PTSD-related behavioral traits in rats exposed to repetitive low-level blast. Treatment with boldine prevented appearance of the blast-induced PTSD-like phenotype including object recognition deficits and exaggerated cued fear learning. Boldine also prevented blast-induced elevation of the metabotropic glutamate receptor (mGluR2) and the N-methyl-D-aspartate receptor 2b (NMDAR2b), but did not reverse decreases in the serotonin 5-HT2A receptor. Representative IbaI immunofluorescence images suggested that Boldine reduced blast-associated microglial process retraction in sensimotor cortex; quantitative morphometric analysis supports this conclusion. Bulk hippocampal RNA-seq did not identify individual genes that remained significant after FDR correction. Exploratory analysis of 85 nominally significant candidates suggested that boldine is associated with coordinated transcriptional changes related to cognition and neurotransmitter transport, consistent with modulation of activity-regulated transcription factors and neuroimmune signaling. These studies suggest that boldine may be beneficial for the neurobehavioral syndromes that follow blast exposure in military Veterans, while highlighting the need for validation in both sexes and in treatment paradigms initiated after symptoms have emerged.
2026-07-18 | GSE338885 | GEO
Project description:We have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control.
2017-08-31 | GSE45462 | GEO
Project description:Rehabilitation Exercise-driven Symbiotic Electrical Stimulation System Can Accelerating Bone Regeneration
2026-08-21 | GSE242160 | 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