Rat Head Research Articles

Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet

Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH.

Reference-free unwarping of single-shot spatiotemporally encoded MRI using asymmetric self-refocused echoes acquisition

This paper presents a phase evolution rewinding algorithm for correcting the geometric and intensity distortions in single-shot spatiotemporally encoded (SPEN) MRI with acquisition of asymmetric self-refocused echo trains. Using the field map calculated from the phase distribution of the source image, the off-resonance induced phase errors are successfully rewound through deconvolution. The alias-free partial Fourier transform reconstruction helps improve the signal-to-noise ratio of the field maps and the output images. The effectiveness of the proposed algorithm was validated through 7T MRI experiments on a lemon, a water phantom, and in vivo rat head. SPEN imaging was evaluated using rapid acquisition by sequential excitation and refocusing (RASER) which produces uniform T2 weighting. The results indicate that the new technique can more robustly deal with the cases in which the images obtained with conventional single-shot spin-echo EPI are difficult to be restored due to serious field variations.

Architectural constraints are a major factor reducing path integration accuracy in the rat head direction cell system.

Head direction cells fire to signal the direction in which an animal's head is pointing. They are able to track head direction using only internally-derived information (path integration)In this simulation study we investigate the factors that affect path integration accuracy. Specifically, two major limiting factors are identified: rise time, the time after stimulation it takes for a neuron to start firing, and the presence of symmetric non-offset within-layer recurrent collateral connectivity. On the basis of the latter, the important prediction is made that head direction cell regions directly involved in path integration will not contain this type of connectivity; giving a theoretical explanation for architectural observations. Increased neuronal rise time is found to slow path integration, and the slowing effect for a given rise time is found to be more severe in the context of short conduction delays. Further work is suggested on the basis of our findings, which represent a valuable contribution to understanding of the head direction cell system.

Immunologically augmented skin flap as a novel dendritic cell vaccine against head and neck cancer in a rat model.

Local recurrence is a major clinical issue following surgical resection in head and neck cancer, and the dissemination and lymph node metastasis of minimal residual disease is relatively difficult to treat due to the lack of suitable therapeutic approaches. In the present study, we developed and evaluated a novel immunotherapy using a skin flap transfer treated with sensitized dendritic cells (DC), termed the “immuno-flap,” in a rat tumor model. After the local round area of skin was resected, SCC-158 cells (a rat head and neck cancer cell line) were inoculated into the muscle surface; lastly, the groin skin flap injected with mature DC was overlaid. Two weeks after the second DC injection, systemic immunological reactions and tumor size were measured. The DC-treated group showed a significant reduction in tumor size compared with the control. Although the induction of CTL activity in spleen cells was marginal, Th1 cytokines such as interleukin-2 and interferon-γ were elevated in the DC-treated group. These results suggest that a novel immunotherapy based on the immuno-flap method has the potential for clinical application to prevent the local recurrence of head and neck cancer patients.

1908 Basic Study for Developing Rat's Head Positioner

1908 Basic Study for Developing Rat's Head Positioner

Impaired generation of high-frequency oscillations in a rat model of schizophrenia

Event Abstract Back to Event Impaired generation of high-frequency oscillations in a rat model of schizophrenia Lauren Harms1*, Deborah Hodgson1, William Fulham1, Markku Penttonen2, Ulrich Schall1, Juanita Todd1 and Patricia Michie1 1 University of Newcastle, Australia 2 University of Jyväskylä, Finland Background: Schizophrenia patients have an impaired capacity to generate high-frequency gamma (>30Hz) oscillations. Gamma oscillations play an integral role in cognition and their reduction in schizophrenia is a candidate neurophysiological mechanism underlying cognitive impairments. The neurobiological and behavioural implications of disrupted gamma oscillations can be best understood using an animal model. Methods: MIA was induced in Wistar rats by administering pregnant rats with Poly (I:C), a viral mimic, at gestational day 19. The offspring grew to adulthood, when they underwent surgery to implant EEG electrodes. A wireless telemetric headstage was fixed to the rat's head and the EEG recorded while rats were exposed to auditory steady-state white noise clicks, presented at a range of frequencies (10-50Hz). Recordings were made from three separate drug-free sessions, then rats were administered MK-801, an NMDAR antagonist, over three separate sessions at escalating doses (0.1, 0.3, 0.5mg/kg). Oscillatory power and inter-trial coherence were extracted for each stimulus frequency. Results: MIA-exposed rats demonstrated a reduction in frontal 50Hz aSSRs. MK-801 dose-dependently reduced these 50Hz aSSRs. Conclusions: MIA in rats altered the trajectory of brain development, affecting systems responsible for the generation of high-frequency gamma oscillations. MK-801, a NMDAR antagonist that also indirectly impairs inhibitory neurotransmission also was found to reduce 50Hz oscillatory activity, perhaps indicating that both MK-801 and MIA are affecting similar neurobiological pathways. Further experiments will focus on the cognitive and neurobiological correlates of MIA-associated reductions in gamma oscillations, with the ultimate goal of furthering our understanding of the neurobiology underlying cognitive impairments in schizophrenia. Keywords: Schizophrenia, EEG, gamma oscillations, animal model, maternal immune activation Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Sensation and Perception Citation: Harms L, Hodgson D, Fulham W, Penttonen M, Schall U, Todd J and Michie P (2015). Impaired generation of high-frequency oscillations in a rat model of schizophrenia. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00207 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Lauren Harms, University of Newcastle, Callaghan, Australia, lauren.harms@newcastle.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lauren Harms Deborah Hodgson William Fulham Markku Penttonen Ulrich Schall Juanita Todd Patricia Michie Google Lauren Harms Deborah Hodgson William Fulham Markku Penttonen Ulrich Schall Juanita Todd Patricia Michie Google Scholar Lauren Harms Deborah Hodgson William Fulham Markku Penttonen Ulrich Schall Juanita Todd Patricia Michie PubMed Lauren Harms Deborah Hodgson William Fulham Markku Penttonen Ulrich Schall Juanita Todd Patricia Michie Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

235 ラット用のヘッドポジショナー作製のための基礎検討

235 ラット用のヘッドポジショナー作製のための基礎検討

Oxidative Stress and Inflammatory Response in Early Stage of Diffuse Axonal Injury in Rats

Objective: To investigate the role of oxidative stress and immunoinflammatory reaction in early stage of diffuse axonal injury (DAI). Methods: 96 adult male SD rats were divided into 2 groups (n = 48 in each): sham group and DAI group. Rat diffuse axonal injury was induced by a rat instant lateral head rotation device, which was developed to let the rat head spin 90 degree at the moment to cause shearing injury. The modified neurological severity score (mNSS), histomorphology, PI staining, GFAP immunofluorescent staining, SOD activity, CAT activity, MDA content and western blotting (IL-6,IL-1, JNK and p-JNK) in parietal cortex were investigated at 6 h, 1 d and 3 d after DAI. Results: The neurological severity scores, GFAP positive cell, PI positive cells, MDA, IL-6, IL-1, JNK and p-JNK were significantly increased and the SOD and CAT activities were decreased after DAI. Conclusion: Oxidative stress and immunoinflammatory reaction played important roles in DAI pathophysiological process in acute phase.

Characterization of Closed Head Impact Injury in Rat.

The closed head impact (CHI) rat models are commonly used for studying the traumatic brain injury. The impact parameters vary considerably among different laboratories, making the comparison of research findings difficult. In this work, numerical CHI experiments were conducted to investigate the sensitivities of intracranial responses to various impact parameters (e.g., impact depth, velocity, and position; impactor diameter, material, and shape). A three-dimensional finite element rat head model with anatomical details was subjected to impact loadings. Results revealed that impact depth and impactor shape were the two leading factors affecting intracranial responses. The influence of impactor diameter was region-specific and an increase in impactor diameter could substantially increase tissue strains in the region which located directly beneath the impactor. The lateral impact could induce higher strains in the brain than the central impact. An indentation depth instead of impact depth would be appropriate to characterize the influence of a large deformed rubber impactor. The experimentally observed velocity-dependent injury severity could be attributed to the “overshoot” phenomenon. This work could be used to better design or compare CHI experiments.

Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.

BackgroundSteroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms.MethodsSteroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels.ResultsThe ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro.ConclusionABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

Gastrodin prevents steroid-induced osteonecrosis of the femoral head in rats by anti-apoptosis

Background Gastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH. Methods All 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups. Results The incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower. Conclusion Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.

COMP-angiopoietin1 potentiates the effects of bone morphogenic protein-2 on ischemic necrosis of the femoral head in rats.

Angiogenesis is considered essential for proper bone regeneration. The purpose of this investigation was to determine if a combined therapy of bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) can potentiate the therapeutic effect of BMP-2 in a rat model of ischemic necrosis of the femoral head (INFH). INFH was surgically induced in the femoral head of rats, and the animals were divided into the following groups: 1) a sham-operated group (sham group), 2) a bovine serum albumin-injected group (BSA group), 3) a BMP-2-injected group (BMP-2 group), and 4) a COMP-Ang1 and BMP-2-injected group (COMP-Ang1 + BMP-2 group) (n = 20/group). Radiologic, histologic, and histomorphometric assessments were performed to assess femoral head morphology, vascular density, and bone resorption activity. Western blots and immunohistochemical staining were performed to evaluate production of BMP-related signaling proteins in C3H10T1/2 cells and tissues. Real-time RT-PCR was performed to investigate expression of the target integrin gene, and the effect of integrin on C3H10T1/2 cells was determined using a cell adhesion assay. Radiographs obtained six weeks after injection revealed better preservation of the architecture of the femoral head in the COMP-Ang1 + BMP-2 group compared with the BSA and BMP-2 groups. Histological findings indicated increased trabecular bone and vascularity and decreased osteoclast bone resorption activity in the COMP-Ang1 + BMP-2 group compared with those in the BSA and BMP-2 groups. The combination of COMP-Ang1 and BMP-2 increased phosphorylation of Smad1/3/5, p38, and Akt. Increased integrin α3 and β1 mRNA expression in the COMP-Ang1 + BMP-2 group promoted cell adhesion. These results suggest that COMP-Ang1 preserved the necrotic femoral head through the potentiation of BMP-2 signaling pathways and angiogenesis. Combination treatment with COMP-Ang1 and BMP-2 may be a clinically useful therapeutic application in INFH.

Downhill exercise-induced changes in gene expression related with macrophage polarization and myogenic cells in the triceps long head of rats.

Macrophages are one of the most heterogenic immune cells involved in skeletal muscle regeneration. After skeletal muscle damage, M1 phenotypes exhibit pro-inflammatory reaction. In a later stage, they are converted to M2 phenotypes with anti-inflammatory properties. To study when gene expressions of macrophage polarization are changed after damage induced by downhill exercise to exhaustion is the objective of this paper. Before (CTRL) and 0 h (G0), 24 h (G24), 48 h (G48) and 72 h (G72) after 18 bouts of downhill exercise, the animals were euthanised, and the triceps were dissected. We measured gene expression of macrophages (CD68 and CD163), myogenic cells (MyoD and myogenin) and quantified cytokine secretion (interleukin (IL)-6, IL-10 and tumour necrosis factor alpha (TNF-α)). The CD68 expression was lower in G72 compared with G24 (P = 0.005) while CD163 was higher in G48 compared with G24 (P = 0.04). The MyoD expression was higher in G72 compared with G0 (P = 0.04). The myogenin expression was lower in G24 compared with CTRL (P = 0.01) and restored in G72 compared with G24 (P = 0.007). The TNF-α was significantly higher at all times after 24 h (all compared with CTRL, with P = 0.03). The CD68 and CD163 expressions behaved distinctly after exercise, which indicates macrophage polarization between 24 and 48 h. The distinct expression of myogenin, concomitantly with MyoD elevation in G72, indicates that myogenic cell differentiation and the significant change of TNF-α level show an important role of this cytokine in these processes.

Activity-dependent sensory signal processing in mechanically responsive slowly conducting meningeal afferents.

Activity-dependent processes in slowly conducting afferents have been shown to modulate conduction and receptive properties, but it is not known how the frequency of action potential firing determines the responses of such fibers to mechanical stimulation. We examined the responses of slowly conducting meningeal afferents to mechanical stimuli and the influence of preceding action potential activity. In hemisected rat heads with adhering cranial dura mater, recordings were made from meningeal nerves. Dural receptive fields of mechanically sensitive afferent fibers were stimulated with a custom-made electromechanostimulator. Sinusoidal mechanical stimuli of different stimulus durations and amplitudes were applied to produce either high-frequency (phasic) or low-frequency (tonic) discharges. Most fibers showed slowing of their axonal conduction velocity on electrically evoked activity at ≥2 Hz. In this state, the peak firing frequency of phasic responses to a 250-ms mechanical stimulus was significantly reduced compared with control. In contrast, the frequency of tonic responses induced by mechanical stimuli of >500 ms did not change. In a rare subtype of afferents, which showed conduction velocity speeding during activity, an increase in the phasic responses to mechanical stimuli was observed. Depending on the axonal properties of the afferent fibers, encoding of phasic components of mechanical stimuli is altered according to the immediate firing history. Preceding activity in mechanoreceptors slowing their conduction velocity seems to provide a form of low-pass filtering of action potential discharges predominantly reducing the phasic component. This may improve discrimination between harmless and potentially harmful mechanical stimuli in normal tissue.

Markerless motion tracking of awake animals in positron emission tomography.

Noninvasive functional imaging of awake, unrestrained small animals using motion-compensation removes the need for anesthetics and enables an animal's behavioral response to stimuli or administered drugs to be studied concurrently with imaging. While the feasibility of motion-compensated radiotracer imaging of awake rodents using marker-based optical motion tracking has been shown, markerless motion tracking would avoid the risk of marker detachment, streamline the experimental workflow, and potentially provide more accurate pose estimates over a greater range of motion. We have developed a stereoscopic tracking system which relies on native features on the head to estimate motion. Features are detected and matched across multiple camera views to accumulate a database of head landmarks and pose is estimated based on 3D-2D registration of the landmarks to features in each image. Pose estimates of a taxidermal rat head phantom undergoing realistic rat head motion via robot control had a root mean square error of 0.15 and 1.8 mm using markerless and marker-based motion tracking, respectively. Markerless motion tracking also led to an appreciable reduction in motion artifacts in motion-compensated positron emission tomography imaging of a live, unanesthetized rat. The results suggest that further improvements in live subjects are likely if nonrigid features are discriminated robustly and excluded from the pose estimation process.

DigiPET: sub-millimeter spatial resolution small-animal PET imaging using thin monolithic scintillators

A new preclinical PET system based on dSiPMs, called DigiPET, is presented. The system is based on thin monolithic scintillation crystals and exhibits superior spatial resolution at low-cost compared to systems based on pixelated crystals. Current dedicated small-rodent PET scanners have a spatial resolution in the order of 1 mm. Most of them have a large footprint, requiring considerable laboratory space. For rodent brain imaging, a PET scanner with sub-millimeter resolution is desired. To achieve this, crystals with a pixel pitch down to 0.5 mm have been used. However, fine pixels are difficult to produce and will render systems expensive. In this work, we present the first results with a high-resolution preclinical PET scanner based on thin monolithic scintillators and a large solid angle. The design is dedicated to rat-brain imaging and therefore has a very compact geometry. Four detectors were placed in a square arrangement with a distance of 34.5 mm between two opposing detector modules, defining a field of view (FOV) of 32 × 32 × 32 mm3. Each detector consists of a thin monolithic LYSO crystal of 32 × 32 × 2 mm3 optically coupled to a digital silicon photomultiplier (dSiPM). Event positioning within each detector was obtained using the maximum likelihood estimation (MLE) method. To evaluate the system performance, we measured the energy resolution, coincidence resolving time (CRT), sensitivity and spatial resolution. The image quality was evaluated by acquiring a hot-rod phantom filled with 18F-FDG and a rat head one hour after an 18F-FDG injection. The MLE yielded an average intrinsic spatial resolution on the detector of 0.54 mm FWHM. We obtained a CRT of 680 ps and an energy resolution of 18% FWHM at 511 keV. The sensitivity and spatial resolution obtained at the center of the FOV were 6.0 cps kBq−1 and 0.7 mm, respectively. In the reconstructed images of the hot-rod phantom, hot rods down to 0.7 mm can be discriminated. In conclusion, a compact PET scanner was built using dSiPM technology and thin monolithic LYSO crystals. Excellent spatial resolution and acceptable sensitivity were demonstrated. Promising results were also obtained in a hot-rod phantom and in rat-brain imaging.

Huogu I formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARγ expression and activating Wnt/LRP5/β-catenin signaling

ObjectiveTo investigate the effects of Huogu I formula on regulation of lipid metabolism in steroid-induced osteonecrosis of the femoral head (SONFH) rats and verify our hypothesis that Huogu I formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma (PPARγ) expression and activating Wnt signaling pathways. MethodsEighty-five rats were divided into four groups: control, model, Huogu 15 g/kg and Huogu 30 g/kg. Six weeks later, animals were anaesthetized, femora were dissected for histopathological examination of the osteonecrotic changes and repair processes, micro computed tomography (Micro-CT)-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The expressions of PPARγ, Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5) and β-catenin were evaluated by immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction analyses. ResultsThe incidence of osteonecrosis, ratio of empty lacuna, adipose tissue area and adipocyte perimeter in the bone marrow were dramatically lower in the Huogu I formula treatment groups. By micro-CT quantification, Huogu I formula treatment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume and vessel thickness of the femoral heads of SONFH rats. Levels of serum lipid in Huogu 15 g/kg and Huogu 30 g/kg groups reduced significantly. Huogu I formula treatment could suppress the expression of PPARγ and increase the expressions of Wnt3a, LRP5 and β-catenin at both protein and mRNA levels. ConclusionThe results of our present study highlight the lipid-lowering potential of Huogu I formula, and provide further evidence of the involvement of the PPARγ inhibition and Wnt/LRP5/β-catenin signaling activation in the effects of Huogu I formula.

The WRAIR projectile concussive impact model of mild traumatic brain injury: re-design, testing and preclinical validation.

The WRAIR projectile concussive impact (PCI) model was developed for preclinical study of concussion. It represents a truly non-invasive closed-head injury caused by a blunt impact. The original design, however, has several drawbacks that limit the manipulation of injury parameters. The present study describes engineering advancements made to the PCI injury model including helmet material testing, projectile impact energy/head kinematics and impact location. Material testing indicated that among the tested materials, 'fiber-glass/carbon' had the lowest elastic modulus and yield stress for providing an relative high percentage of load transfer from the projectile impact, resulting in significant hippocampal astrocyte activation. Impact energy testing of small projectiles, ranging in shape and size, showed the steel sphere produced the highest impact energy and the most consistent impact characteristics. Additional tests confirmed the steel sphere produced linear and rotational motions on the rat's head while remaining within a range that meets the criteria for mTBI. Finally, impact location testing results showed that PCI targeted at the temporoparietal surface of the rat head produced the most prominent gait abnormalities. Using the parameters defined above, pilot studies were conducted to provide initial validation of the PCI model demonstrating quantifiable and significant increases in righting reflex recovery time, axonal damage and astrocyte activation following single and multiple concussions.

Synchrotron radiation X-ray microtomography and histomorphometry for evaluation of chemotherapy effects in trabecular bone structure

Three-dimensional microtomography has the potential to examine complete bones of small laboratory animals with very high resolution in a non-invasive way. One of the side effects caused by some chemotherapy drugs is the induction of amenorrhea, temporary or not, in premenopausal women, with a consequent decrease in estrogen production, which can lead to bone changes. In the present work, the femur heads of rats treated with chemotherapy drugs were evaluated by 3D histomorphometry using synchrotron radiation microcomputed tomography. Control animals were also evaluated for comparison. The 3D tomographic images were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. Results showed significant differences in morphometric parameters measured from the 3D images of femur heads of rats in both analyzed groups.

Cajan leaf combined with bone marrow-derived mesenchymal stem cells for the treatment of osteonecrosis of the femoral head.

The aim of the present study was to observe the curative effect of traditional Chinese cajan leaves, combined with administration of bone marrow-derived mesenchymal stem cells (BMSCs), on osteonecrosis of the femoral head (ONFH) in rats and to investigate the underlying mechanisms. A total of 40 rat ONFH models were established through liquid nitrogen freezing and were subsequently divided into groups: A, control; B, treated with cajan leaf; C, treated with BMSCs and D, treated with cajan leaf combined with BMSCs. Samples were obtained 30 days following treatment, and immunohistochemical staining of vascular endothelial growth factor (VEGF) and image analysis were performed. Chondrocytes and vascular endothelial cells were stained as a result of immunohistochemical staining and group D exhibited markedly deeper staining, and a significantly larger number of stained cells, compared with group A. Thus, in the present study, cajan leaf combined with BMSCs was shown to promote VEGF expression and improve ONFH repair.