Effects of electrical stimulation on rat limb regeneration, a new look at an old model.
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ABSTRACT:
SUBMITTER: Leppik LP
PROVIDER: S-EPMC4683620 | biostudies-other | 2015 Dec
REPOSITORIES: biostudies-other
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Project description:Different species respond differently to severe injury, such as limb loss. In species that regenerate, limb loss is met with complete restoration of the limbs' form and function, whereas in mammals the amputated limb's stump heals and scars. In in vitro studies, electrical stimulation (EStim) has been shown to promote cell migration, and osteo- and chondrogenesis. In in vivo studies, after limb amputation, EStim causes significant new bone, cartilage and vessel growth. Here, in a rat model, the stumps of amputated rat limbs were exposed to EStim, and we measured extracellular matrix (ECM) deposition, macrophage distribution, cell proliferation and gene expression changes at early (3 and 7 days) and later stages (28 days). We found that EStim caused differences in ECM deposition, with less condensed collagen fibrils, and modified macrophage response by changing M1 to M2 macrophage ratio. The number of proliferating cells was increased in EStim treated stumps 7 days after amputation, and transcriptome data strongly supported our histological findings, with activated gene pathways known to play key roles in embryonic development and regeneration. In conclusion, our findings support the hypothesis that EStim shifts injury response from healing/scarring towards regeneration. A better understanding of if and how EStim controls these changes, could lead to strategies that replace scarring with regeneration.
| S-EPMC6685943 | biostudies-literature
Project description:BackgroundFunctional Electrical Stimulation (FES) is a technique that aims to rehabilitate or restore functionality of skeletal muscles using external electrical stimulation. Despite the success achieved within the field of FES, there are still a number of questions that remain unanswered. One way of providing input to the answers is through the use of computational models.MethodsThis paper describes the development of an anatomically based computer model of the motor neurons in the lower limb of the human leg and shows how it can be used to simulate electrical signal propagation from the beginning of the sciatic nerve to a skeletal muscle. One-dimensional cubic Hermite finite elements were used to represent the major portions of the lower limb nerves. These elements were fit to data that had been digitised using images from the Visible Man project. Nerves smaller than approximately 1 mm could not be seen in the images, and thus a tree-branching algorithm was used to connect the ends of the fitted nerve model to the respective skeletal muscle. To simulate electrical propagation, a previously published mammalian nerve model was implemented and solved on the anatomically based nerve mesh using a finite difference method. The grid points for the finite difference method were derived from the fitted finite element mesh. By adjusting the tree-branching algorithm, it is possible to represent different levels of motor-unit recruitment.ResultsTo illustrate the process of a propagating nerve stimulus to a muscle in detail, the above method was applied to the nerve tree that connects to the human semitendinosus muscle. A conduction velocity of 89.8 m/s was obtained for a 15 mum diameter nerve fibre. This signal was successfully propagated down the motor neurons to a selected group of motor units in the muscle.ConclusionAn anatomically and physiologically based model of the posterior motor neurons in the human lower limb was developed. This model can be used to examine the effect of external stimulation on nerve and muscle activity, as may occur, for example, in the field of FES.
| S-EPMC2228306 | biostudies-literature
Project description: Not available
| S-EPMC2631055 | biostudies-literature
Project description:Attempts to explain abducens vulnerability have centered around the petroclival segment of its pathway in the skull base, in particular, its relations to the Dorello's canal and the petrosphenoidal ligament of Grüber. This study aims to contribute to the definition of the Dorello's canal and to the understanding of abducens vulnerability from an evolutionary perspective. The petroclival region and the Dorello's canal in particular were examined in a sample of 86 primate skulls. The sample contains 20 Pan troglodytes (common chimpanzee), 35 Gorilla gorilla, 20 Pongo pygmaeus (orangoutan), and 11 Hylobates moloch (gibbon) skulls. Distance between the petrous apex and tip of the posterior clinoid process was measured using a 10-mm scale that was inserted into the endocranium. Complete absence of the Grüber ligament and an uninterrupted osseous circumference of the Dorello's canal (foramen) was demonstrated in all nonhuman primate species. Whatever the reason for the morphological difference between the human and ape Dorello's canal, it is without a doubt suggestive of the source of vulnerability of the abducens nerve, as the ligament of Grüber, unique to the human configuration, renders the contents of the Dorello's canal susceptible to compression against the cranial base.
| S-EPMC3312418 | biostudies-other
Project description:To address limitations in current approaches for treating large peripheral nerve defects, the presented study evaluated the feasibility of functional material-mediated physical stimuli on peripheral nerve regeneration. Electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) nanofibers were utilized to deliver mechanical actuation-activated electrical stimulation to nerve cells/tissues in a non-invasive manner. Using morphologically and piezoelectrically optimized nanofibers for neurite extension and Schwann cell maturation based on in vitro experiments, piezoelectric nerve conduits were synthesized and implanted in a rat sciatic nerve transection model to bridge a critical-sized sciatic nerve defect (15 mm). A therapeutic shockwave system was utilized to periodically activate the piezoelectric effect of the implanted nerve conduit on demand. The piezoelectric nerve conduit-mediated mechano-electrical stimulation (MES) induced enhanced peripheral nerve regeneration, resulting in full axon reconnection with myelin regeneration from the proximal to the distal ends over the critical-sized nerve gap. In comparison, a control group, in which the implanted piezoelectric conduits were not activated in vivo, failed to exhibit such nerve regeneration. In addition, at both proximal and distal ends of the implanted conduits, a decreased number of damaged myelination (ovoids), an increased number of myelinated nerves, and a larger axonal diameter were observed under the MES condition as compared to the control condition. Furthermore, unlike the control group, the MES condition exhibited a superior functional nerve recovery, assessed by walking track analysis and polarization-sensitive optical coherence tomography, demonstrating the significant potential of the piezoelectric conduit-based physical stimulation approach for the treatment of peripheral nerve injury.
| S-EPMC10582163 | biostudies-literature
Project description:Background and objectiveTranscranial Burst Electrical Stimulation (tBES) is an innovative non-invasive brain stimulation technique that combines direct current (DC) and theta burst stimulation (TBS) for brain neuromodulation. It has been suggested that the tBES protocol may efficiently induce neuroplasticity. However, few studies have systematically tested neuromodulatory effects and underlying neurophysiological mechanisms by manipulating the polarity of DC and TBS patterns. This study aimed to develop the platform and assess neuromodulatory effects and neuronal activity changes following tBES.MethodsFive groups of rats were exposed to anodal DC combined with intermittent TBS (tBES+), cathodal DC combined with continuous TBS (tBES-), anodal and cathodal transcranial direct current stimulation (tDCS+ and tDCS-), and sham groups. The neuromodulatory effects of each stimulation on motor cortical excitability were analyzed by motor-evoked potentials (MEPs) changes. We also investigated the effects of tBES on both excitatory and inhibitory neural biomarkers. We specifically examined c-Fos and glutamic acid decarboxylase (GAD-65) using immunohistochemistry staining techniques. Additionally, we evaluated the safety of tBES by analyzing glial fibrillary acidic protein (GFAP) expression.ResultsOur findings demonstrated significant impacts of tBES on motor cortical excitability up to 30 min post-stimulation. Specifically, MEPs significantly increased after tBES (+) compared to pre-stimulation (p = 0.026) and sham condition (p = 0.025). Conversely, tBES (-) led to a notable decrease in MEPs relative to baseline (p = 0.04) and sham condition (p = 0.048). Although tBES showed a more favorable neuromodulatory effect than tDCS, statistical analysis revealed no significant differences between these two groups (p > 0.05). Additionally, tBES (+) exhibited a significant activation of excitatory neurons, indicated by increased c-Fos expression (p < 0.05), and a reduction in GAD-65 density (p < 0.05). tBES (-) promoted GAD-65 expression (p < 0.05) while inhibiting c-Fos activation (p < 0.05), suggesting the involvement of cortical inhibition with tBES (-). The expression of GFAP showed no significant difference between tBES and sham conditions (p > 0.05), indicating that tBES did not induce neural injury in the stimulated regions.ConclusionOur study indicates that tBES effectively modulates motor cortical excitability. This research significantly contributes to a better understanding of the neuromodulatory effects of tBES, and could provide valuable evidence for its potential clinical applications in treating neurological disorders.
| S-EPMC10749301 | biostudies-literature
Project description:We report the application of RNA sequencing technology for transcriptomics analysis of the effects of electrical stimulation on rat denervated gastrocnemius muscle. Muscle samples were selected for gene expression analyses，corresponding to the following categories: Sham operation rats, (SHAM, n = 3), sciatic nerve injury rats (DN, n = 3), and sciatic nerve injury with electrical stimulation (DN-SM, n = 3). A total of 14,334 genes (DEGs) were detected in this study.
2020-07-01 | GSE117440 | GEO
Project description:Bone Tissue engineering (BTE) has recently been introduced as an alternative to conventional treatments for large non-healing bone defects. BTE approaches mimic autologous bone grafts, by combining cells, scaffold, and growth factors, and have the added benefit of being able to manipulate these constituents to optimize healing. Electrical stimulation (ES) has long been used to successfully treat non-healing fractures and has recently been shown to stimulate bone cells to migrate, proliferate, align, differentiate, and adhere to bio compatible scaffolds, all cell behaviors that could improve BTE treatment outcomes. With the above in mind we performed in vitro experiments and demonstrated that exposing Mesenchymal Stem Cells (MSC)?+?scaffold to ES for 3 weeks resulted in significant increases in osteogenic differentiation. Then in in vivo experiments, for the first time, we demonstrated that exposing BTE treated rat femur large defects to ES for 8 weeks, caused improved healing, as indicated by increased bone formation, strength, vessel density, and osteogenic gene expression. Our results demonstrate that ES significantly increases osteogenic differentiation in vitro and that this effect is translated into improved healing in vivo. These findings support the use of ES to help BTE treatments achieve their full therapeutic potential.
| S-EPMC5910383 | biostudies-literature
Project description:BackgroundDamage to lower motor neuron causes denervation and degeneration of the muscles affected. Experimental and clinical studies of muscle denervation in lower extremities demonstrated that direct electrical stimulation (ES) of muscle can prevent denervation atrophy and restore contractility. The aim of this study was to identify possible myogenic effect of ES on denervated forearm and hand muscles in persons with spinal cord injury (SCI) and tetraplegia.MethodsThis prospective interventional study with repeated measurement design included 22 patients aged 48·6 (± 15·7), 0·25 (0·1/46) years after spinal cord lesion, AIS A-D. In each patient, two electrophysiologically-confirmed denervated muscles in the hand and forearm were analyzed - one extrinsic (Extensor Carpi Ulnaris - ECU) and one intrinsic (1st Dorsal Interosseus - IOD1). Muscles were stimulated for 33 min, five times per week over a 12-weeks period. Using ultrasonography (USG), muscle thickness (MT) and pennation angle (PA) of these muscles were determined at start and end of the stimulation period.FindingsMT of IOD1 increased from 6·3 mm (± 3·2 mm) to 9·2 mm (± 2·4 mm) (p = 0·004) and the PA from 5·5° (± 3·0°) to 11° (± 2·2°) (p = 0·001). The corresponding values for the ECU were 5·5 mm (± 2·5 mm) to 7·0 mm (± 2·2 mm) (p = 0·039) and 5·5° (± 3·4°) to 9·4° (± 3·8°) (p = 0·005), respectively. The correlation of MT between baseline and completion was r = 0·58 (p = 0·037) for the ECU and r = 0·63 (p = 0·008) for the IOD1.Interpretation12 weeks of direct muscle stimulation increases the MT and PA of the denervated intrinsic and extrinsic hand muscles studied.FundingSwiss Paraplegic Centre, Switzerland.
| S-EPMC8671101 | biostudies-literature
Project description:Increasing evidence highlights bipolar disorder as being associated with impaired neurogenesis, cellular plasticity, and resiliency, as well as with cell atrophy or loss in specific brain regions. This has led most recent research to focus on the possible neuroprotective effects of medications, and particularly interesting findings have emerged for lithium. A growing body of evidence from preclinical in vitro and in vivo studies has in fact documented its neuroprotective effects from different insults acting on cellular signaling pathways, both preventing apoptosis and increasing neurotrophins and cell-survival molecules. Furthermore, positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. These recent evidences suggest the potential utility of lithium in the treatment of neurodegenerative diseases, neurodevelopmental disorders, and hypoxic-ischemic/traumatic brain injury, with positive results at even lower lithium doses than those traditionally considered to be antimanic. The aim of this review is to briefly summarize the potential benefits of lithium salts on neuroprotection and neuroregeneration, emphasizing preclinical and clinical evidence suggesting new therapeutic potentials of this drug beyond its mood stabilizing properties.
| S-EPMC4946830 | biostudies-other