Cylinder Test Research Articles

Uncertainty quantification of material parameters in modeling coupled metal and high explosive experiments

Experiments involving the coupling of metal and high explosives (HE) are of notable defense-related interest, and we seek to refine the uncertainty quantification associated with models of such experiments. In particular, our focus is on how uncertainty related to the metal constitutive model challenges our ability to infer high explosive model parameters when analyzing focused science experiments. We consider three focused experiments involving an HE accelerating metal: small plate tests with tantalum/LX-14 and tantalum/LX-17 pairings as well as a tantalum/LX-17 cylinder test. For all three models, we perform sensitivity analysis to ascertain the influence of metal strength on the coupled experimental response. Moreover, we calibrate each model in a Bayesian setting and study the quantification of metal strength on the inference of the HE parameters. Based on our results, we offer guidance for future metal/HE experiments.

Deletion of the Transient Receptor Potential Melastatin 2 Gene Mitigates the 6-Hydroxydopamine-Induced Parkinson's Disease-Like Pathology.

Pharmacological inhibition of the transient receptor potential melastatin 2 (TRPM2), an oxidative stress-activated calcium channel, was previously reported to be protective in Parkinson's disease (PD). However, the inhibitors used were not TRPM2 specific, so the involvement of this channel in PD remains unclear. Here, for the first time, Trpm2 partial (+ / -) and complete (- / -) knockout mice underwent stereotaxic surgery for PD induction. Six-hydroxydopamine was injected in the right striatum. On days 3 and 6, motor behavior tests (cylinder, apomorphine, and pole test) were performed. On day 7, brains were collected for dopaminergic neuron immunostaining. Our results showed that Trpm2 + / - male and female mice had reduced motor impairment and dopaminergic neuron death after PD induction. In addition, Trpm2 - / - male and female mice showed absent or lesser motor deficit and the dopaminergic neuronal loss was no longer observed. These findings suggest that TRPM2 is involved in the PD-like pathology and that targeting TRPM2 may possibly represent a potential neuroprotective strategy for PD.

Bacteriophages targeting Enterococcus faecalis enhance the therapeutic efficacy of levodopa in an MPTP-induced Parkinson’s disease mouse model with E. faecalis gut colonization

Despite the intensive research on gut microbiome-associated diseases over the past 20 years, pharmacological methods for effectively eliminating pathobionts remain unsatisfactory. This study investigated the therapeutic potential of bacteriophages against Enterococcus faecalis, in which bacterial tyrosine decarboxylase (TDC) converts orally administered levodopa (L-DOPA) to dopamine, in an MPTP mouse model of Parkinson’s disease (PD). E. faecalis bacteriophages PBEF62, PBEF66, and PBEF67 (4 × 1010 PFU total/200 µl/day), and E. faecalis cells (2 × 109 CFU/200 µl/day) were orally administered at 2-h intervals before every MPTP (i.p.) and/or L-DOPA (p.o.) treatments for 13 days. The relative abundances of E. faecalis cells and bacteriophages in the feces peaked at 4 and 12 h after administration and gradually decreased by 12 and 48 h, respectively. While the administration of E. faecalis cells eliminated the beneficial effect of L-DOPA on MPTP-induced behavioral deficits, as assessed by cylinder and rotarod tests, the co-administration of bacteriophages with bacterial cells restored this effect. The modulating effects of L-DOPA, E. faecalis, and bacteriophages on PD behavior were closely associated with choline acetyltransferase expression levels in the striatum but not with tyrosine hydroxylase in the substantia nigra of each group. Recurrence and extinction of PD behaviors following treatment with E. faecalis and/or bacteriophages were also coincident with the dopamine levels in the blood and brain tissues of PD mice. The effectiveness of L-DOPA was restored after the three types of E. faecalis bacteriophages selectively eliminated E. faecalis cells, along with the TDC gene copies and transcripts responsible for converting L-DOPA to dopamine in the gastrointestinal tract. In conclusion, a combination of bacteriophages PBEF62, PBEF66, and PBEF67 targeting E. faecalis demonstrates potential as a valuable supplement to L-DOPA therapy for PD.

Complex High‐Cyclic Loading in an Accumulation Model for Sand

ABSTRACTExperimental evidence indicates that multidimensional cyclic loading of soils causes larger accumulation of deformations than equivalent one‐dimensional loading. The response of sand to high‐cyclic loading with 10,000 cycles and up to four‐dimensional stress paths (i.e., four independent oscillating components) is examined in 120 triaxial and hollow cylinder tests in this work to extend these findings. With increasing number of oscillating stress components, the accumulation of permanent strains tends to increase. It is demonstrated that the definition of the multidimensional strain amplitude incorporated in the high‐cycle accumulation (HCA) model can account for this. The validation of the HCA model for complex cyclic loading is complemented by the simulation of model tests on monopile foundations of offshore wind turbines subjected to multidirectional cyclic loading, for which the consideration of spatially variable cyclic loading with nonconstant load amplitudes in the HCA model is discussed. For this purpose, an extension of the HCA model considering multiple strain amplitudes is presented.

Recovery after human bone marrow mesenchymal stem cells (hBM-MSCs)-derived extracellular vesicles (EVs) treatment in post-MCAO rats requires repeated handling.

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal treatment of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose or single dose of EVs. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work at the tested dose and frequency, and that a single cumulative dose of EVs further improves the neurological function recovered during handling. These results show the importance of rehabilitation in combination with other treatments such as EVs, and highlight how extensive behavioral testing might influence functional recovery after stroke.

Positron emission tomography neuroimaging of [18F]fluorodeoxyglucose uptake and related behavior in the Pink1-/- rat model of Parkinson disease.

Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The Pink1-/- rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in Pink1-/- and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior. Pink1-/- (n = 12) and WT (n = 14) rats were imaged by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified a priori for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam. Relative glucose metabolism was significantly different in Pink1-/- rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, Pink1-/- rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra. FDG PET reveals abnormalities in relative regional brain glucose metabolism in Pink1-/- rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the Pink1-/- PD model.

Modeling Stochastical Particle Rebound based on High Velocity Experiments

Abstract Solid particle erosion is a major deterioration process which contributes to performance deterioration of modern axial compressors. The prediction of this deterioration process requires the correct computation of particle movement through the machine and their resulting impacts on the effected components. Especially for particles with high Stokes numbers the movement is determined mainly by the particle wall interaction, which is described by coefficients of restitution. Today, they are derived from experiments featuring high particle velocities and target materials, which are representative for turbomachinery applications. In this study, an already published rebound model is optimized for particle materials and velocities within high pressure compressors. The statistical spread of the rebound experiment is evaluated and the implementation into the rebound model is shown, which improves the prediction capability of the model. The model is implemented into a CFD software and numerical simulations are performed. The model is applied to a cylinder test specimen within a sand blast facility. The simulation shows the importance of the stochastics of the rebound, which is often neglected in particle wall models. Moreover, the numerical study shows requirements for the test specimen and its positioning in the experimental setup, which are prerequisites for the derivation of the coefficients of restitution using two dimensional particle evaluation equipment.

Effects of dopaminergic neuron degeneration on osteocyte apoptosis and osteogenic markers in 6-OHDA male rat model of Parkinson's disease

Parkinson's disease (PD) and osteoporosis are prevalent chronic conditions that impact a significant proportion of the aging population. Observational and longitudinal studies consistently demonstrate that individuals with PD face an elevated risk of osteoporosis and reduced bone mineral density compared to control groups. However, there is currently no experimental evidence demonstrating the impact of dopaminergic neuron degeneration on bone metabolism. In the present study, we used a male rat model of PD induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the left medial forebrain bundle (MFB) to evaluate the effect of dopaminergic neuron lesion on certain parameters of bone metabolism. To confirm the dopaminergic neuron lesion, cylinder and Rotarod tests were applied to rats injected with 6-OHDA or vehicle. Osteocyte density and viability were determined through histology and TUNEL assay. Western Blot and immunohistochemistry analysis were performed to investigate whether dopaminergic degeneration influences the expression of some apoptotic markers (Caspase 3 and Cytochrome C) and some osteogenic markers (ALP, OCN, and RUNX2). Our findings show that the dopaminergic lesion resulting from the injection of 6-OHDA was successfully confirmed through behavioral tests. Furthermore, the degeneration of dopaminergic neurons induced by 6-OHDA leads to apoptosis of osteocytes associated with a significant reduction in the tissue expression of the studied osteogenic markers. Thus, our study provides evidence that 6-OHDA-induced degeneration of dopaminergic neurons leads to osteocyte apoptosis, which may contribute to the development of some signs of osteoporosis.

Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104

Neuroactive steroids reduce mortality, decrease edema, and improve functional outcomes in preclinical and clinical traumatic brain injury (TBI) studies. In this study, we tested the efficacy of two related novel neuroactive steroids, NTS-104 and NTS-105, in a rat model of TBI. NTS-104 is a water-soluble prodrug of NTS-105, a partial progesterone receptor agonist. To investigate the effects of NTS-104 on TBI recovery, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion injury or sham surgery and were treated with vehicle or NTS-104 (10 ​mg/kg, intramuscularly) at 4, 10, 24, and 48 ​h post-TBI. The therapeutic time window was also assessed using the neuroactive steroid NTS-105 (3 ​mg/kg, intramuscularly). Edema in the parietal cortex and hippocampus, measured at 3 days post-injury (DPI), was reduced by NTS-104 and NTS-105. NTS-105 was effective in reducing edema when given at 4, 10, or 24 ​h post-injury. Sensorimotor deficits in the cylinder test at 3 DPI were ameliorated by NTS-104 and NTS-105 treatment. Cognitive recovery, assessed with cue and contextual fear conditioning and retention of the water maze task assessed subacutely 1–3 weeks post-injury, also improved with NTS-104 treatment. Cortical and hippocampal atrophy at 22 DPI did not improve, indicating that NTS-104/NTS-105 may promote post-TBI cognitive recovery by controlling edema and other processes. These results demonstrate that NTS-104/NTS-105 is a promising therapeutic approach to improve motor and cognitive recovery after moderate TBI.

Effect of recycled aggregates with different parent strength and fly ash on flexural strength of recycled aggregate concrete prisms

Fast consumption of conventional ingredients of concrete and waste generated due to demolishing old buildings is a multi-fold problem in the concrete industry. Hence the sustainable alternative of it is the need of the day. In this research work effect of binary blending of demolished waste and fly ash on the flexural strength of plain concrete prism is presented. The properties of aggregates and cement are evaluated. The physical and chemical properties of fly ash were determined. Recycled aggregates from demolished waste with different mix ratios (1:2:4 and 1:1.5:3) were used. Optimization of recycled aggregates; by evaluating concrete cylinders in 12 batches; showed 35% as optimum. At the optimum dosage of recycled aggregates fly ash was used from 2.5% to 15% with an increment of 2.5% to optimize its dosage. Compressive strength test of the standard-size cylinders and their comparison with control concrete showed a 10% dosage of a fly as the optimum percentage to replace the cement in the concrete matrix. Using both optimized dosages of recycled aggregates and fly ash prism specimens of900mmx150mmx300mm were cast in four batches. The beam specimens were cured for 28 days followed by an evaluation of flexural strength and deflection under centric load in the universal testing machine. Test results of flexural strength (only 15% loss) showed good potential for both waste materials in the concrete matrix. Recycled aggregate with higher parent strength showed better performance than its other counterparts. With higher-strength recycled aggregates residual flexural strength was recorded as equal to 93%. For all specimens recorded deflection was within the allowable limits of ACI-318.

A Simplified Calibration Procedure for DEM Simulations of Granular Material Flow

The discrete element method (DEM) has emerged as an essential computational tool in geotechnical engineering for the simulation of granular materials, offering significant advantages over traditional continuum-based methods such as the finite element method (FEM) and the finite difference method (FDM). The DEM’s ability to model particle-level interactions, including contact forces, rotations, and particle breakage, allows for a more precise understanding of granular media behavior under various loading conditions. However, accurate DEM simulations require meticulous calibration of input parameters, such as particle density, stiffness, and friction, to effectively replicate real-world behavior. This study proposes a simplified calibration procedure, intended to be conducted prior to any granular material flow DEM modeling, based on three fundamental physical tests: bulk density, surface friction, and angle of repose. The ability of these tests, conducted on dry quartz sand, to accurately determine DEM micromechanical parameters, was validated through numerical simulation of cylinder tests with varying height-to-radius ratios. The results demonstrated that this calibration approach effectively reduced computational complexity while maintaining high accuracy, with validation errors of 0% to 12%. This research underscores the efficacy of simplified DEM calibration methods in enhancing the predictive reliability of simulations, particularly for sand modeling in geotechnical applications.

Calibration of Discrete Element Method Parameters for a High-Fidelity Lunar Regolith Simulant Considering the Effects of Realistic Particle Shape

The Discrete Element Method (DEM) is an important tool for investigating the geotechnical properties of lunar regolith. The accuracy of DEM simulations largely depends on precise particle modeling and the appropriate selection of mesoscopic parameters. To enhance the reliability and accuracy of the DEM in lunar regolith studies, this paper utilized the high-fidelity IRSM-1 lunar regolith simulant to construct a DEM model with realistic particle shapes and conducted an angle of repose (AoR) simulation test. The optimal DEM parameters were calibrated using a combination of the Plackett–Burman test, steepest ascent test, and Box–Behnken design. The results indicate that the sliding friction coefficient, rolling friction coefficient, and surface energy significantly influence the simulation AoR. By optimizing against the measured AoR using a second-order regression model, the optimal parameter values were determined to be 0.633, 0.401, and 0.2, respectively. Under these optimal parameters, the error between the simulation and experimental AoR was 2.1%. Finally, the calibrated mesoscopic parameters were validated through a lifting cylinder test, showing an error of 6.3% between the simulation and experimental results. The high similarity in the shape of the AoR further confirms the accuracy and reliability of the parameter calibration method. This study provides a valuable reference for future DEM-based research on the mechanical and engineering properties of lunar regolith.

Experimental and numerical studies on the collapse of Titanium alloy ring-stiffened cylinder

This paper investigates the collapse of ring-stiffened Titanium alloy cylinders used for subsea resource exploration under hydrostatic pressure through experimental and numerical methods. Extensive material tests were first conducted on Titanium alloy specimens to obtain the fundamental mechanical properties and variation characteristics. Then, a 4236 mm-long test cylinder was fabricated with an inner radius of 650 mm and a thickness (ts) of 18.85 mm. The initial geometric imperfection was measured at evenly-spaced positions in the axial direction and 48 locations around the circumference by dial gauges. Afterward, the test cylinder was transferred into a custom hyperbaric pressure vessel and pressurized to collapse. As to the numerical analysis, a user-defined material subroutine implementing the incremental J2 deformation theory was developed to predict plastic bifurcation pressure. Moreover, a nonlinear finite element (FE) model, which incorporated the measured geometric imperfection and material nonlinearity, was used to reproduce the experiment. The numerical results were found to exhibit reasonably good agreement with the test data. In addition, parametric studies were conducted regarding material properties, geometric parameters, and imperfection sizes on the load-carrying capacity of Titanium alloy ring-stiffened cylinders.

Post-fire flexural buckling and resistances of square recycled aggregate concrete-filled stainless steel tube (RACFSST) columns

The flexural buckling behaviour and residual resistances of square recycled aggregate concrete-filled stainless steel tube (RACFSST) columns after exposure to fire are studied in this paper, based on experiments and numerical modelling. Twelve column specimens, fabricated from concretes with three recycled coarse aggregate replacement ratios (0%, 35% and 70%), were tested after exposure to the ISO 834 standard fire for 0 min (i.e. at ambient temperature), 15 min, 30 min and 45 min. The experimental investigation included heating of specimens, cylinder tests as well as post-fire initial global geometric imperfection measurements, tensile coupon tests and pin-ended column tests. The test setups, procedures and results were fully reported and the ductility indices, lateral deflection distributions and longitudinal strains were discussed and analysed. A numerical investigation was afterwards carried out, where the test results were used to validate thermal and mechanical finite element models; upon validation, parametric studies were conducted to expand the test data bank over a wider range of cross-section dimensions and member lengths. On the basis of the test and numerical data, the relevant design rules for square natural aggregate concrete-filled carbon steel tube columns at ambient temperature, as set out in the European code, Australian/New Zealand standard and American specification, were assessed, using post-fire material properties, for their applicability to square RACFSST columns after exposure to fire. It was found from the assessment results that the three design codes resulted in overall accurate and consistent post-fire flexural buckling resistance predictions but some were unsafe.

Modulation of human induced neural stem cell-derived dopaminergic neurons by DREADD reveals therapeutic effects on a mouse model of Parkinson’s disease

BackgroundStem cell-based therapy is a promising strategy for treating Parkinson’s disease (PD) characterized by the loss of dopaminergic neurons. Recently, induced neural stem cell-derived dopaminergic precursor cells (iNSC-DAPs) have been emerged as a promising candidate for PD cell therapy because of a lower tumor-formation ability. Designer receptors exclusively activated by designer drugs (DREADDs) are useful tools for examining functional synaptic connections with host neurons.MethodsDREADD knock-in human iNSCs to express excitatory hM3Dq and inhibitory hM4Di receptors were engineered by CRISPR. The knock-in iNSCs were differentiated into midbrain dopaminergic precursor cells (DAPs) and transplanted into PD mice. The various behavior test such as the Apomorphine-induced rotation test, Cylinder test, Rotarod test, and Open field test were assessed at 4, 8, or 12 weeks post-transplantation with or without the administration of CNO. Electrophysiology were performed to assess the integrated condition and modulatory function to host neurons.ResultsDREADD expressing iNSCs were constructed with normal neural stem cells characteristics, proliferation ability, and differentiation potential into dopaminergic neuorns. DAPs derived from DREADD expressing iNSC showed matched function upon administration of clozapine N-oxide (CNO) in vitro. The results of electrophysiology and behavioral tests of transplanted PD mouse models revealed that the grafts established synaptic connections with downstream host neurons and exhibited excitatory or inhibitory modulation in response to CNO in vivo.ConclusioniNSC-DAPs are a promising candidate for cell replacement therapy for Parkinson’s disease. Remote DREADD-dependent activation of iNSC-DAP neurons significantly enhanced the beneficial effects on transplanted mice with Parkinson’s disease.

Quality Management In Ready-Mix Concrete Production In Zambia

The construction industry, a significant contributor to global economies, is projected to yield substantial economic output by 2030 of around $135 trillion. Central to construction is concrete, a widely used material. Ready-mix concrete (RMC), a specialised form of concrete, is gaining prominence due to its rapid setting and superior quality. In Zambia, the increasing demand for RMC highlights the need for stringent quality management to hedge potential structural risks. This study aimed to determine the quality management in ready-mix concrete production in Zambia. Employing a parallel convergent mixed-methods research design to achieve the objectives, qualitative data was collected through semi-structured interviews and desk study and quantitative data was gathered through a structured questionnaire and an observation checklist. The findings of the study reveal that while guidelines exist, adherence varies. Regulatory bodies for standards, engineering and construction play pivotal roles in overseeing RMC quality. However, their execution faces inconsistencies and challenges due to limited resources and a lack of sense of responsibility. Quality control practices were investigated unveiling variations in forward, immediate, and retrospective control phases. Notable trends in proper storage and equipment calibration showed a commitment to precision. Immediate control practices, encompassing sampling and non-compliance management, demonstrated both positive aspects and areas for improvement. Retrospective control showed commitment to comprehensive strength testing and minimal towards split cylinder testing and on-site slump evaluation. In the realm of quality assurance (QA), RMC facilities show substantial adherence to documented QA standard operating procedures and thorough raw material inspections. However, deficiencies in batching and mixing practices and limited adoption of modern weighing systems require improvement. The study recommends creating an industry association for collaboration, enhancing standardised practices, introducing third-party quality audits, and proposing compulsory RMC standards to boost progress in the Zambian RMC industry. Key Words: Quality Management, Ready Mix Concrete, Observation, Desk Study, Zambia.

PET imaging of synaptic vesicle glycoprotein 2 subtype A for neurological recovery in ischemic stroke.

[18F]SynVesT-1 is a novel radiopharmaceutical for assessing synaptic density in vivo. This study aims to investigate the potential of [18F]SynVesT-1 positron emission tomography (PET) in evaluating neurological recovery in the rat model of ischemic stroke, and to compare its performance with [18F]FDG PET. Sprague-Dawley rats were subjected to photothrombotic cerebral infarction, and safinamide was administered intraperitoneally from day 3 to day 14 post-stroke to alleviate neurological deficits. Cylinder test and forelimb placing test were performed to assess the neurological function. MRI, [18F]SynVesT-1 PET/CT and [18F]FDG PET/CT imaging were used to evaluate infarct volume, synaptic density, and cerebral glucose metabolism pre- and post-treatment. [18F]SynVesT-1 and [18F]FDG PET images were compared using Statistical Parametric Mapping (SPM) and region of interest (ROI)-based analysis. Post-mortem histological analysis was performed to validate PET images. Safinamide treatment improved behavioral outcomes in stroke-damaged rats. Both [18F]SynVesT-1 and [18F]FDG PET detected stroke-induced injury, with the injured region being significantly larger in [18F]FDG PET than in [18F]SynVesT-1 PET. Compared with the saline group, radiotracer uptake in the injured area significantly increased in [18F]SynVesT-1 PET after safinamide treatment, whereas no notable change was observed in [18F]FDG PET. Additionally, [18F]SynVesT-1 PET imaging showed a better correlation with neurological function recovery than [18F]FDG PET. Post-mortem analysis revealed increased neuronal numbers, synaptic density, and synaptic neuroplasticity, as well as decreased glia activation in the stroke-injured area after treatment. [18F]SynVesT-1 PET effectively quantified spatiotemporal dynamics of synaptic density in the rat model of stroke, and showed different capabilities in detecting stroke injury and neurological recovery compared with [18F]FDG PET. The utilization of [18F]SynVesT-1 PET holds promise as a potential non-invasive biomarker for evaluating ischemic stroke in conjunction with [18F]FDG PET.

Spontaneously Hypertensive Rats Present Exacerbated Focal Stroke Behavioral Outcomes.

This study aimed to analyze the effects of systemic arterial hypertension (SAH) in a model of permanent ischemic stroke (focal ischemia due to thermocoagulation of pial vessels) on sensorimotor function (cylinder test and patch removal test), behavioral tasks (novelty habituation memory open field task) and cerebral infarct size in adult male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 42 days after the occurrence of a stroke. We observed that the stroke caused asymmetry in the front paws and delayed adhesive removal. These effects were spontaneously reduced in WKY rats, but not in SHR. Short- and long-term novelty habituation memories were abolished by stroke in WYK and SHR. On the 3rd day after stroke, the size of the focal cerebral infarct was the same in WKY and SHR. However, on the 7th day, the infarct size decreased in WKY rats, but not SHR. These results suggested that SAH impairment of sensorimotor recovery in rats subjected to cerebral ischemia could be related to augmented focal cerebral infarct size. Moreover, the behavioral tasks used in this study were unaffected by Systemic Arterial Hypertension. Our results highlight the need for animal models of comorbidities in stroke research.

Lactate administration causes long-term neuroprotective effects following neonatal hypoxia-ischemia

Neonatal hypoxia-ischemia (HI) is one of the main causes of mortality and long-term disabilities in newborns, and the only clinical approach to treat this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models of HI. Lactate is a preferential metabolic substrate of the neonatal brain and has already been shown to produce beneficial neuroprotective outcomes in neonatal animals exposed to HI. Here, we administered lactate as a treatment in neonatal rats previously exposed to HI and evaluated the impact of this treatment in adulthood. Seven-day-old (P7) male and female Wistar rats underwent permanent common right carotid occlusion combined with an exposition to a hypoxic atmosphere (8% oxygen) for 60 min. Animals were assigned to one of four experimental groups: HI, HI+LAC, SHAM, SHAM+LAC. Lactate was administered intraperitoneally 30 min and 2 h after hypoxia in HI+LAC and SHAM+LAC groups, whereas HI and SHAM groups received vehicle. Animals were tested in the behavioral tasks of negative geotaxis and righting reflex (P8), cylinder test (P24), and the modified neurological severity score was calculated (P25). Open field (OF), and novel object recognition (NOR) were evaluated in adulthood. Animals were killed at P60, and the brains were harvested and processed to evaluate the volume of brain injury. Our results showed that lactate administration reduced the volume of brain lesion and improved sensorimotor and cognitive behaviors in neonatal, juvenile, and adult life in HI animals from both sexes. Thus, lactate administration might be considered as a potential neuroprotective strategy for the treatment of neonatal HI, which is a prevalent disorder affecting newborns.

Neuroprotective effects of Hibiscus sabdariffa var. altissima on cerebral ischemia‒Reperfusion injury in rats

BackgroundHibiscus sabdariffa var. altissima, which is known for its high-quality fiber, is commonly used in Traditional Chinese Medicine (TCM) for its diuretic, choleretic, analgesic, antitussive, and hypotensive effects. Furthermore, the flowers have been used to treat diabetes, hypertension, atherosclerosis, and obesity. However, there are no studies assessing its neuroprotective effects on cerebral ischemia, unlike the sabdariffa variety known for its neuroprotective effects. Therefore, this study was aimed to investigate the potential efficacy of Hibiscus sabdariffa var. altissima extract (HAS) and its underlying mechanism on oxidative stress and neuroinflammation during cerebral ischemia-reperfusion (I/R) injury. MethodsA model of cerebral ischemia was established in male Wistar rats through middle cerebral artery occlusion (MCAO) and reperfusion. Rats were randomly divided into the sham, IR, IR + HSA100, IR + HSA200, IR + HSA400 and IR + Eda groups and were treated for 14 consecutive days. The neurological deficit score and the cylinder test were performed to assess neurological impairment. Oxidative stress was determined by measuring the levels of malondialdehyde (MDA) and antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured to evaluate antioxidant activities. In addition, the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were also determined. ResultsOur results demonstrated that HSA significantly ameliorated neurological impairment and reduced the volume of brain infarct. HSA also decreased the levels of MDA and enhanced the antioxidant activities of GSH, SOD and CAT in brain tissues. Furthermore, HSA decreased the expression of the proinflammatory cytokines TNF-α, IL-1β and IL-6 in the serum. ConclusionThese findings demonstrated that HSA exhibited a potential neuroprotective effect against cerebral I/R injury, possibly by improving oxidative stress and attenuating inflammatory responses. Therefore, HSA could be used as a potential therapeutic option for cerebral ischemic injuries.