Detection of locomotion deficit in a post-traumatic syringomyelia rat model using automated gait analysis technique
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ABSTRACT:
SUBMITTER: Pukale D
PROVIDER: S-EPMC8584658 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSyringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions.MethodsA rat PTSM model consisting of a laminectomy at the C7 to T1 level followed by a parenchymal injection of 2 μL quisqualic acid (QA) and an injection of 5 μL kaolin in the subarachnoid space was utilized 6 weeks after initial surgery, parenchymal fluid and cerebrospinal fluid (CSF) were collected, and the osmolality of fluids were analyzed. Immunohistochemistry (IHC), metabolomics analysis using LC-MS, and mass spectrometry-based imaging (MSI) were performed on injured and laminectomy-only control spinal cords.ResultsWe demonstrated that the osmolality of the local parenchymal fluid encompassing syrinxes was higher compared to control spinal cords after laminectomy, indicating a local osmotic imbalance due to SM injury. Moreover, we also found that parenchymal fluid is more hypertonic than CSF, indicating establishment of a local osmotic gradient in the PTSM injured spinal cord (syrinx site) forcing fluid into the spinal cord parenchyma to form and/or expand syrinxes. IHC results demonstrated upregulation of betaine, ions, water channels/transporters, and enzymes (BGT1, AQP1, AQP4, CHDH) at the syrinx site as compared to caudal and rostral sites to the injury, implying extensive local osmoregulation activities at the syrinx site. Further, metabolomics analysis corroborated alterations in osmolality at the syrinx site by upregulation of small molecule osmolytes including betaine, carnitine, glycerophosphocholine, arginine, creatine, guanidinoacetate, and spermidine.ConclusionsIn summary, PTSM results in local osmotic disturbance that propagates at 6 weeks following initial injury. This coincides with and may contribute to syrinx formation/expansion.
| S-EPMC10895764 | biostudies-literature
Project description:Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.
| S-EPMC8423938 | biostudies-literature
Project description:Epilepsy is a common neurologic condition frequently investigated using rodent models, with seizures identified by electroencephalography (EEG). Given technological advances, large datasets of EEG are widespread and amenable to machine learning approaches for identification of seizures. While such approaches have been explored for human EEGs, machine learning approaches to identifying seizures in rodent EEG are limited. We utilized a predesigned deep convolutional neural network (DCNN), GoogLeNet, to classify images for seizure identification. Training images were generated through multiplexing spectral content (scalograms), kurtosis, and entropy for two-second EEG segments. Over 2200 h of EEG data were scored for the presence of seizures, with 95.6% of seizures identified by the DCNN and a false positive rate of 34.2% (1.52/h), as compared to visual scoring. Multiplexed images were superior to scalograms alone (scalogram-kurtosis-entropy 0.956 ± 0.010, scalogram 0.890 ± 0.028, t(7) = 3.54, p < 0.01) and a DCNN trained specifically for the individual animal was superior to using DCNNs across animals (intra-animal 0.960 ± 0.0094, inter-animal 0.811 ± 0.015, t(30) = 5.54, p < 0.01). For this dataset the DCNN approach is superior to a previously described algorithm utilizing longer local line lengths, calculated from wavelet-decomposition of EEG, to identify seizures. We demonstrate the novel use of a predesigned DCNN constructed to classify images, utilizing multiplexed images of EEG spectral content, kurtosis, and entropy, to rapidly and objectively identifies seizures in a large dataset of rat EEG with high sensitivity.
| S-EPMC10517002 | biostudies-literature
Project description:The identification of the initial contact (IC) and toe off (TO) events are crucial components of running gait analyses. To evaluate running gait in real-world settings, robust gait event detection algorithms that are based on signals from wearable sensors are needed. In this study, algorithms for identifying gait events were developed for accelerometers that were placed on the foot and low back and validated against a gold standard force plate gait event detection method. These algorithms were automated to enable the processing of large quantities of data by accommodating variability in running patterns. An evaluation of the accuracy of the algorithms was done by comparing the magnitude and variability of the difference between the back and foot methods in different running conditions, including different speeds, foot strike patterns, and outdoor running surfaces. The results show the magnitude and variability of the back-foot difference was consistent across running conditions, suggesting that the gait event detection algorithms can be used in a variety of settings. As wearable technology allows for running gait analyses to move outside of the laboratory, the use of automated accelerometer-based gait event detection methods may be helpful in the real-time evaluation of running patterns in real world conditions.
| S-EPMC6480623 | biostudies-literature
Project description:It has recently been suggested that a deficit in time processing may be considered a cognitive marker of Post-Traumatic Stress Disorder (PTSD). However, the neural correlates of this cognitive deficit in PTSD remain unknown. Voxel-based morphometry and supra-second perceptual time processing data from 8 participants with PTSD and 19 healthy controls have been examined. In line with previous investigations, PTSD patients overestimated the duration of the displayed stimuli. Moreover, their time estimation was more variable than that of controls. Critically, compared to controls, a higher grey matter volume was reported in most of neural regions of PTSD canonically associated with supra-second perceptual timing. These data provide preliminary evidence that the abnormal neuroplasticity of this neural network may be responsible for the altered experience of time in PTSD.
| S-EPMC8794066 | biostudies-literature
Project description:Motor deficits can significantly affect the completion of daily life activities and have a negative impact on quality of life. Consequently, motor function is an important behavioral endpoint to measure for in vivo pathophysiologic studies in a variety of research areas, such as toxicant exposure, drug development, disease characterization, and transgenic phenotyping. Evaluation of motor function is also critical to the interpretation of cognitive behavioral assays, as many rely on intact motor abilities to derive meaningful data. As such, gait analysis is an important component of behavioral research and can be achieved by manual or video-assisted methods. Manual gait analysis methods, however, are prone to observer bias and are unable to capture many critical parameters. In contrast, automated video-assisted gait analysis can quickly and reliably assess gait and locomotor abnormalities that were previously difficult to collect manually. Here, we describe the evaluation of gait and locomotion in rodents using the automated Noldus CatWalk XT system. We include a step-by-step guide for running an experiment using the CatWalk XT system and discuss theory and considerations when evaluating rodent gait. The protocol and discussion provided here act as a supplemental resource to the manual for this commercially available system and can assist CatWalk users in their experimental design and implementation. © 2021 Wiley Periodicals LLC.
| S-EPMC8363132 | biostudies-literature
Project description:Insect locomotion represents a fundamental example of neuronal oscillating circuits generating different motor patterns or gaits by controlling their phase coordination. Walking gaits are assumed to represent stable states of the system, often modeled as coupled oscillators. This view is challenged, however, by recent experimental observations, in which in vitro locust preparations consistently converged to synchronous rhythms (all legs oscillating as one), a locomotive pattern never seen in vivo. To reconcile this inconsistency, we developed a modeling framework to capture the trade-off between the two competing mechanisms: the endogenous neuronal circuitry, expressed in vitro, and the feedback mechanisms from sensory and descending inputs, active only in vivo. We show that the ubiquitously observed double-tripod walking gait emerges precisely from this balance. The outcome is a short-lived meta-stable double-tripod gait, which transitions and alternates with stable idling, thus recovering the observed intermittent bouts of locomotion, typical of many insects' locomotion behavior.
| S-EPMC6352547 | biostudies-literature
Project description:BackgroundAn important factor contributing to the development and occurrence of post-traumatic epilepsy (PTE) is neuroinflammation and oxidative stress. The effects of celecoxib include inhibiting inflammatory reactions and antioxidant stress and reducing seizures, making it a potential epilepsy treatment solution.ObjectiveTo observe the effect of celecoxib on early epilepsy in post-traumatic epilepsy rats. Methods: Twenty-four adult healthy male Sprague-Dawley rats were randomly assigned to three groups: sham-operated, PTE, and celecoxib. A rat model of PTE was established by injecting ferrous chloride into the right frontal cortex. Afterward, the behavior of rats was observed and recorded. 3.0T superconducting magnetic resonance imaging (MRI) was used to describe the changes in ADC values of the brain. HE and Nissl staining were also used to detect the damage to frontal lobe neurons. Furthermore, the expression of COX-2 protein in the right frontal lobe was detected by Western blot. Moreover, the contents of IL-1 and TNF-α in the right frontal lobe were detected by enzyme-linked immunosorbent assay.ResultsCompared with the PTE group, the degree of seizures in rats treated with celecoxib declined dramatically (P < 0.05). Celecoxib-treated rats had significant decreases in tissue structural damage and cell death in the brain. The results of the MRI showed that celecoxib reduced the peripheral edema zone and ADC value of the cortex around the damaged area of the right frontal lobe in the celecoxib-treatment group, which was significantly decreased compared with the PTE group (P < 0.05). Furthermore, celecoxib decreased the expression of COX-2, IL-1β, and TNF-α in brain tissue (P < 0.05).ConclusionsIn PTE rats, celecoxib significantly reduced brain damage and effectively reduced seizures. As a result of celecoxib's ability to inhibit inflammation, it can reduce the edema caused by injury in rat brain tissue.
| S-EPMC10710164 | biostudies-literature
Project description:BackgroundPost-stroke depression (PSD) occurs in at least one-third of stroke survivors, is associated with worse functional outcomes and increased mortality, and is frequently underdiagnosed and undertreated.ObjectiveTo evaluate the effectiveness of an electronic medical record-based system intervention to improve the proportion of veterans screened and treated for PSD.DesignQuasi-experimental study comparing PSD screening and treatment among veterans receiving post-stroke outpatient care one year prior to the intervention (the control group) to those receiving outpatient care during the intervention period (the intervention group); contemporaneous data from non-study sites included to assess temporal trends in depression diagnosis and treatment.ParticipantsVeterans hospitalized for ischemic stroke and/or receiving primary care (PC) or neurology outpatient follow-up within six months post-stroke at two (Veterans Affairs) VA Medical Centers.InterventionsWe formed clinical improvement teams at both sites. Teams developed PSD screening and treatment reminders and designed tailored implementation strategies for reminder use in PC and neurology clinics.Main measuresProportion screened for PSD within 6 months post-stroke; proportion screening positive for PSD who received an appropriate treatment action within 6 months post-stroke.Key resultsIn unadjusted analyses, PSD screening was performed within 6 months for 85% of intervention (N = 278) vs. 50% of control (N = 374) patients (OR 6.2 , p < 0.001), and treatment action was received by 83% of intervention vs. 73% of control patients who screened positive (OR 1.8 p = 0.13). After adjusting for intervention, site and number of follow-up visits, intervention patients were more likely to be screened (OR 4.8, p < 0.001) and to receive a treatment action if screened positive (OR 2.45, p = 0.05). Analyses of temporal trends in non-study sites revealed no trend toward general increase in PSD detection or treatment.ConclusionsAutomated depression screening in primary and specialty care can improve detection and treatment of PSD.
| S-EPMC3138982 | biostudies-literature
Project description:A promising treatment strategy for spinal cord injury (SCI) is to reduce inhibition from chondroitin sulfate proteoglycans (CSPGs). For example, administering intracellular ? peptide (ISP) can improve the ability of axons to cross inhibitory CSPGs and improve function in rodent models of SCI. To translate such treatments into the clinic, we need robust and sensitive methods for studying rodent models. In this study, we applied a newly developed suite of quantitative gait analysis tools: gait analysis instrumentation and technology optimized for rodents (GAITOR), which consists of an arena and open-source software (AGATHA: automated gait analysis through hues and areas). We showed that GAITOR can be used to detect subtle functional improvements (measured by hindlimb duty factor imbalance) in rats following ISP administration in a T10 hemisection injury model. We demonstrated that SCI-specific parameters (right paw placement accuracy and phase dispersion) can be easily added to GAITOR to track recovery. We confirmed the gait observations via retrograde tracer uptake. We concluded that GAITOR is a powerful tool for measuring recovery after moderate/mild SCI, and could be used to replace expensive/inflexible commercially-available gait analysis techniques.
| S-EPMC6382578 | biostudies-literature