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Background: Neuropathic pain (NP) is a complex disease that remains challenging to treat. Low-frequency dense-and-disperse (DD) electroacupuncture (EA) has been used as adjuvant therapy for neuropathic pain; however, its analgesic effect decreases as stimulation time increases, or when it is repeatedly used. We hypothesized that a new frequency parameter could improve the effectiveness of EA, and aimed to compare the efficacy and duration of the analgesic effect between classic DD-EA and non-repetitive and non-sequential frequency (random frequency (RF)-EA) in neuropathic rats. Furthermore, the effect of RF-EA at local traditional acupuncture point locations versus auricular vagus nerve stimulation (aVNS) was evaluated. Methods: Male Wistar rats with peripheral neuropathy were subjected to a single session of DD-EA or RF-EA for 20 or 40 min at ST36 + GB34. An additional group of rats was treated with RF-EA for 20 min using aVNS at the appropriate ear point locations. Paw pressure test, von Frey filaments and spontaneous pain scores were evaluated. Sham-operated rats were used as controls. Results: In all, 20 min of RF-EA reversed hyperalgesia (for 24 h) and allodynia (for 8 h), showing a longer analgesic effect than DD-EA. Both RF-EA and DD-EA induced partial inhibition of spontaneous pain for 8 h. Forty minutes of DD-EA did not interfere with the NP phenomena; however, RF-EA induced significant long-term analgesia. aVNS induced an analgesic effect similar to local stimulation. Conclusion: This pilot study shows that RF-EA at both local traditional acupuncture point and auriculotherapy point locations induces long-lasting analgesia in neuropathic rats, and more effectively so than classical DD-EA.

Blast-induced traumatic brain injury is the signature injury of modern military conflicts. To more fully understand the effects of blast exposure, we placed rats in different holder configurations, exposed them to blast overpressure, and assessed the degree of eye and brain injury. Anesthetized Long-Evans rats received blast exposures directed at the head (63 kPa, 195 dB-SPL) in either an "open holder" (head and neck exposed; n = 7), or an "enclosed holder" (window for blast exposure to eye; n = 15) and were compared to non-blast exposed (control) rats (n = 22). Outcomes included optomotor response (OMR), electroretinography (ERG), and spectral domain optical coherence tomography (SD-OCT) at 2, 4, and 6 months post-blast, and cognitive function (Y-maze) at 3 months. Spatial frequency and contrast sensitivity were reduced in ipsilateral blast-exposed eyes in both holders (p 0.01), while contralateral eyes showed greater deficits with the enclosed holder (p 0.05). Thinner retinas (p 0.001) and reduced ERG a- and b- wave amplitudes (p 0.05) were observed for both ipsilateral and contralateral eyes with the enclosed, but not the open, holder. Rats in the open holder showed cognitive deficits compared to rats in the enclosed holder (p 0.05). Overall, the animal holder configuration used in blast exposure studies can significantly affect outcomes. Enclosed holders may cause secondary damage to the contralateral eye by concussive injury or blast wave reflection off the holder wall. Open holders may damage the brain via rapid head movement (contrecoup injury). These results highlight additional factors to be considered when evaluating patients with blast exposure or developing models of blast injury.

To evaluate the use of mirror test in an open field arena as a visual function assessment tool in a rodent model of diabetes. Male Sprague-Dawley rats were divided into diabetic rats, that received intraperitoneal streptozotocin (55 mg/kg body weight) for induction of diabetes, and control rats that similarly received citrate buffer. Rats with a blood glucose level of more than 20 mmol/L were considered diabetic. Blood glucose was monitored weekly throughout the experimental period. General behavioural assessment of the rats was done at week 12 post-induction using open field arena, followed by visual-behavioural assessment with mirror and reversed mirror added in the arena. Subsequently, rats were euthanised and subjected to haematoxylin and eosin staining (H&E) staining to assess changes in retinal morphology. In the open field test, diabetic rats showed a lesser number of zone crossings (3.73-fold, p

Introduction: Venovenous extracorporeal membrane oxygenation (VV ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV ECMO in ARDS rats. Methods: A total of 18 Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV ECMO was established through cavoatrial cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV ECMO. Results: Following ARDS induced by OA, ten rats were successfully established on VV ECMO without failure and survived the ECMO procedure. VV ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygenation. VV ECMO was associated with decreased lung injury score, wet/dry weight ratio, and fluid leakage into airspaces. Conclusion: We have established a reliable, economical, and functioning ARDS rat model of VV ECMO.

Introduction Traditional cigarette use influences cost-benefit decision making by promoting impulsive choice. However, the impact of nicotine exposure via electronic nicotine delivery systems on impulsivity remains unclear. Hence, the present study examined the short- and long-term effects of nicotine vapor on impulsive choice. Methods Twenty-four adult male rats were trained in the delay discounting task to choose between small immediate food rewards and large delayed food rewards. After 24 days of training in the task rats were exposed to vapor containing either 0, 12, or 24 mg/mL of nicotine for 10 days. To validate inhalation of nicotine vapor serum cotinine levels were analyzed on exposure days 1, 5, and 10 using enzyme-linked immunosorbent assay. Following vapor exposure, rats were retrained in the discounting task until rats displayed stable responding and the effects of nicotine vapor on choice preference were assessed. Results Rats exposed to 12 and 24 mg/mL nicotine vapor displayed higher serum cotinine levels than control rats exposed to 0 mg/mL vapor. There were no differences in impulsive choice between any vapor exposure groups when tested 15 days after exposure, across 6 days of stable responding, suggesting that nicotine vapor does not have long lasting effects on impulsive choice. Interestingly, a subsequent nicotine vapor challenge revealed short-term increases in impulsive choice immediately following a single exposure to 24 mg/mL nicotine vapor, relative to choice preference immediately following exposure to 0 mg/mL vapor. Conclusions These results suggest that exposure to nicotine vapor causes immediate, short-term increases in impulsive choice. Implications E-cigarette use is increasing at an alarming rate, particularly among adolescents and young adults. This is concerning given the lack of research into the effects of nicotine vapor exposure on the brain and behavior. The present study describes a viable rodent model of human e-cigarette use and suggests that exposure to nicotine vapor produces short-term increases in impulsive choice.

Purpose: To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia. Materials and Methods: Male rats were allocated into 4 groups: sham (S), sham quercetin (SQ), ischemia (I), and ischemia quercetin (IQ). Groups SQ and IQ received quercetin (50mg/kg) before and after surgery. Groups I and IQ had their left renal vessels clamped for 60 minutes. All animals were euthanized four weeks after the procedure, and serum urea and creatinine levels were measured. Renal weight and volume, cortex-non-cortex area ratio (C-NC), cortical volume (CV), glomerular volumetric density (Vv[glom]), volume-weighted glomerular volume (VWGV) and number of glomeruli per kidney (N[glom]) were evaluated by stereological methods. Results were considered statistically significant when p

BACKGROUND Near-infrared spectroscopy can detect changes in tissue oxygenation postoperatively that predict flap necrosis. The authors hypothesized that this technology can be applied along with topical nitroglycerin to measure an improvement in tissue oxygenation that correlates with tissue salvage. METHODS Dorsal, random pattern flaps measuring 10 × 3 cm were raised using Sprague-Dawley rats. Tissue oxygenation was measured after flap elevation in 10 locations using the ViOptix Intra.Ox. Animals were divided into three groups that received 30 mg of topical nitroglycerin daily, twice-daily, or not at all. Oxygenation measurements were repeated on postoperative day 1 and animals were euthanized on day 7 and evaluated for tissue necrosis. RESULTS Tissue necrosis was greatest in controls (51.3 mm) compared to daily (28.8 mm) and twice-daily nitroglycerin (18.8 mm; p = 0.035). Three flap perfusion zones were identified: healthy (proximal, 50 mm), necrotic (distal, 20 mm), and watershed. Immediate postoperative tissue oxygenation was highest in healthy tissue (57.2 percent) and decreased to 33.0 and 19.3 percent in the watershed and necrotic zones, respectively (p < 0.001). One day after treatment with nitroglycerin, oxygenation in the healthy zone did not increase significantly (mean difference, -1.5 percent). The watershed (17.8 percent; p < 0.001) and necrotic zones (16.3 percent; p

Background: Lipid homeostasis and gut flora can be related to many metabolic diseases, especially autism. Lipid metabolism in the brain can control neuronal structure and function and can also take part in signal transduction pathways to control metabolism in peripheral tissues, especially in the liver. Impaired phospholipid metabolism promotes oxidative stress and neuroinflammation and is, therefore, directly related to autism. Objective: The effect of propionic acid (PPA) toxicity on lipid homeostasis in the gut-liver-brain axis was evaluated to understand their inter-connection. Cytosolic phospholipase A2 (cPLA2) concentration and activity was measured in autistic model and protective role of omega-3 (ω-3) and vitamin B12 was evaluated. Methods: Animals were divided into five groups: Group I (control group); Group II (autistic model treated with neurotoxic dose of PPA); Group III (treated with vitamin B12 (16.7 mg/kg/day) for 30 days post PPA treatment); Group IV (treated with ω-3 (200 mg/kg body weight/day) for 30 days post PPA treatment; Group V (combined dose of ω-3 and Vitamin B12, for 30 days post PPA treatment). Phospholipase A2 activity and protein expression level in the liver homogenate of all the groups was analyzed by western blotting and was compared to brain cPLA2. Results: PPA increased the levels of liver and brain cPLA2. However, independent or combined treatment with ω-3 and vitamin B12 was effective in neutralizing its effect. Moreover, PPA-induced dysbiosis, which was ameliorated with the above treatments. Conclusions: This study showed the role of cPLA2 as a lipid metabolism marker, related to PPA-induced inflammation through a highly interactive gut-liver-brain axis.

The purpose of this study was to evaluate the use of Fiji Image J application for digital fundus image analysis of retinal vessel diameter in diabetic retinopathy rat model. Male Sprague-Dawley rats, weighing 200-250 grams, were divided into two groups: normal and diabetic. The diabetes was induced by intraperitoneal (IP) injection of streptozotocin (STZ, 55 mg/kg body weight). Normal rats received IP citrate buffer. Fundus images were captured at week 0, 6 and 12 post-induction to observe changes in retinal veins and arteries. Images obtained were then analyzed using Fiji Image J software. Retinal venous diameter was increased in both groups at week 6 and 12 compared to baseline (p

Objectives The underlying mechanisms behind the therapeutic and side effects of deep brain stimulation (DBS) need further investigation. The utilization of transgenic mouse lines is a suitable approach to better understand the cellular and network effects of DBS. However, not many bilateral DBS studies have been conducted in mice. This might be due to a lack of commercially available bilateral DBS constructs.Materials and Methods We developed an approach to perform repetitive long-term DBS in freely moving mice. In this study, we implanted an in-house custom-made DBS construct containing two bipolar concentric electrodes to target the subthalamic nucleus (STN) bilaterally. Subsequently, we stimulated half of the animals with clinically relevant parameters three to five times a week with a duration of 20 min for ten weeks. Several behavioral tests were conducted of which the open field test (OFT) is shown to validate the reliability of this electrode construct and implantation method. Furthermore, we performed fiber photometry measurements to show the acute effect of STN-DBS on serotonin network activity in the dorsal raphe nucleus.Results Repetitive DBS and long-term behavioral testing were performed without complications. STN-DBS resulted in an increase of the distance traveled in the OFT and a reduction of calcium levels in serotonergic neurons of the dorsal raphe nucleus. None of the mice had lost their electrodes and postmortem evaluation of the tissue showed accurate targeting of the STN without excessive gliosis.Conclusion The DBS electrode construct and implantation method described can be used for long-term DBS studies to further investigate the mechanisms underlying DBS.

We designed a novel malabsorptive procedure named as jejunal-ileal loop bipartition (JILB), in which a jejunal-ileal loop is created to reduce the effective length of food chyme passage in the small bowel, but without exclusion of any segment of the intestine. This study is to investigate the feasibility and efficacy of JILB on weight loss and glycemic control in obese diabetic mouse model. High-fat diet-induced C57BL/6 mice with typical obese and diabetic phenotypes were randomly divided into two groups according to the surgical procedure performed, including JILB (n = 8) and sham group (n = 8). Age-matched naive C57BL/6 mice fed with rodent chow diet were adopted as normal controls. Body weight, food intake, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and oral glucose tolerance test (OGTT) were measured in vivo before and 2, 4, and 8 weeks after surgery. Plasma glucagon-like peptide 1 (GLP-1) was assayed before and 15 min after oral glucose challenge at the 8th week postoperatively. Comparing to the sham animals, JILB group consumed similar amount of food, but had lower body weight after surgery (P

Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). To appropriately evaluate new therapies for infarct-mediated reentrant arrhythmia in the preclinical setting, chronologic characterization of the preclinical animal model pathophysiology is critical. This study aimed to evaluate the rigor and reproducibility of mmVT incidence in a rodent model of HF. We hypothesize a progressive increase in the incidence of mmVT as the duration of HF increases. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation or SHAM surgery and were maintained for either 6 or 10 wk. At end point, SHAM and HF rats underwent echocardiographic and invasive hemodynamic evaluation. Finally, rats underwent electrophysiologic (EP) assessment to assess susceptibility to mmVT and define ventricular effective refractory period (ERP). In 6-wk HF rats (n = 20), left ventricular (LV) ejection fraction (EF) decreased (P < 0.05) and LV end-diastolic pressure (EDP) increased (P < 0.05) compared with SHAM (n = 10). Ten-week HF (n = 12) revealed maintenance of LVEF and LVEDP (P > 0.05), (P > 0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and 6-wk HF (P = 0.0016) and ERP prolongation (P = 0.0186). The incidence of mmVT and ventricular ERP did not differ between 6- and 10-wk HF (P = 1.0000), (P = 0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the 6- and 10-wk period post-MI, no echocardiographic, invasive hemodynamic, or electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF. NEW & NOTEWORTHY Rodent model of ischemic cardiomyopathy exhibits a plateau of inducible monomorphic ventricular tachycardia incidence between 6 and 10 wk postinfarction.

Abnormal joint kinematics are commonly reported in the acute and chronic stages of recovery after anterior cruciate ligament (ACL) injury and have long been mechanistically implicated as a primary driver in the development of post-traumatic osteoarthritis (PTOA). Though strongly theorized, it is unclear to what extent biomechanical adaptations after ACL injury culminate in the development of PTOA, as data that directly connects these factors does not exist. Using a pre-clinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on joint kinematics and the pathogenetic mechanisms involved in the development of PTOA. Thirty-two, sixteen-week-old Long-Evans rats were exposed to a non-invasive ACL injury. Marker-less deep learning software (DeepLabCut) was used to track animal movement for sagittal-plane kinematic analyses and micro computed tomography was used to evaluate subchondral bone architecture at days 7, 14, 28 and 56 following injury. There was a significant decrease in peak knee flexion during walking (p

The article presents an analysis of current literature covering general information, as well as clinical and experimental research on autism spectrum disorder. Autism is a complex mental disorder. A growing body of literature suggests the association of autism spectrum disorder with dysfunction of the autonomic nervous system, especially those affecting the gastrointestinal tract and bladder. In addition, there are problems with nutrition, metabolism, immune and endocrine systems, and microbiota. Prevalence of autism has increased significantly over the past 40 years. As more and more children with autism become adults, understanding this condition throughout life is of paramount importance. Although many research has focused on understanding how diagnosis and treatment can help little children, few are focused on adults with autism and how primary care groups can better help these people. Despite significant progress toward identifying the factors influencing the development of autism spectrum disorder, the etiology of the disease remains uncertain. In this regard, scientists are trying to obtain models of autism in rodents to continue further research. Based on the data obtained during clinical and experimental researches, a hypothesis about the possible role of the purinergic system in the pathogenesis of autism spectrum disorder is considered. The results are encouraging, but further research is required. Thus, somatic disorders can worsen the main symptoms of autism, which affect communication and behavior functioning. In this regard, further research is necessary, including in a rodent model of autism spectrum disorder to contribute to identifying the possible causes of the disorder.

Background Tracheal transplantation seems to be the logical step in the process of reconstruction of the trachea following a long-segment resection, which is usually done to treat malignant disease or benign stenosis of the airway caused by a traumatic, congenital, inflammatory, or iatrogenic lesion. Immunosuppression following transplant is essential but not ideal after oncoresection. Methods The tracheal allografts, harvested from Sprague Dawley rats, were implanted in the Wistar strain rat. The harvested tracheal grafts were divided into groups and subgroups, based on the layers of trachea, method of decellularization, and immunosuppression. The antigenicity of different layers of trachea and the effect of various decellularization methods were studied within three time frames, that is, day 3, 9, and 15. Result On structural analysis, the day 3 and day 15 samples showed no meaningful comparison could be made, due to extensive neutrophil infiltration in all three layers. The day 9 tracheal grafts showed loss of epithelium, with no signs of regeneration in most of the allografts. The subepithelial lymphoid infiltration was found to be severe in nonimmunosuppressed allografts. The group in which both inner and outer layers were removed showed moderate-to-severe infiltrate of lymphoid cells in all the allografts, but there was no cartilage loss, irrespective of the method of decellularization. The irradiated specimens retained the cartilage but showed extensive ischemic damage. Conclusion Rat trachea is a good model for tracheal transplant research but not adequately sturdy to sustain mechanical debridement. Irradiation and chemical decellularization eliminates the immune response but causes intense ischemic damage. Out of the three time frames, day 9 seemed to be the best to study the immune response. To substantiate the results obtained in this study, the immunohistochemical study of the allografts is needed to be performed among a larger group of animals.

Synapse loss is a hallmark of Alzheimer’s disease (AD) and correlates with cognitive decline. The validation of a noninvasive in vivo imaging approach to quantify synapse would greatly facilitate our understanding of AD pathogenesis and assist drug developments for AD. As animal models of neurodegenerative and neuropsychiatric disorders play a critical role in the drug discovery and development process, a robust, objective, and translational method for quantifying therapeutic drug efficacy in animal models will facilitate the drug development process. In this study, we tested the quantification reliability of the SV2A PET tracer, [18F]SynVesT-1, in a mouse model of AD (APP/PS1) and wild-type controls, and developed a simplified quantification method to facilitate large cohort preclinical imaging studies. We generated nondisplaceable binding potential (BPND) and distribution volume ratio (DVR) values using the simplified reference tissue model (SRTM) on the 90-min dynamic PET imaging data, with brain stem and cerebellum as the reference region, respectively. Then, we correlated the standardized uptake value ratio (SUVR)-1 and SUVR averaged from different imaging windows with BPND and DVR, using brain stem and cerebellum as the reference region, respectively. We performed homologous competitive binding assay and autoradiographic saturation binding assay using [18F]SynVesT-1 to calculate the Bmax and Kd. Using brain stem as the reference region, the averaged SUVR-1 from 30 to 60 min postinjection correlated well with the BPND calculated using SRTM. Using cerebellum as the reference region, the averaged SUVR from 30 to 60 min postinjection correlated well with the SRTM DVR. From the homologous competitive binding assay and autoradiographic saturation binding assay, the calculated the Bmax and Kd were 4.5–18 pmol/mg protein and 9.8–19.6 nM, respectively, for rodent brain tissue. This simplified SUVR method provides reasonable SV2A measures in APP/PS1 mice and their littermate controls. Our data indicate that, in lieu of a full 90-min dynamic scan, a 30-min static PET scan (from 30 to 60 min postinjection) would be sufficient to provide quantification data on SV2A expression, equivalent to the data generated from kinetic modeling. The methods developed here are readily applicable to the evaluation of therapeutic effects of novel drugs in this rodent model using [18F]SynVesT-1 and small animal PET.

C(60) is a potent antioxidant that has been reported to substantially extend the lifespan of rodents when formulated in olive oil (C(60)-OO) or extra virgin olive oil (C60-EVOO). Despite there being no regulated form of C(60)-OO, people have begun obtaining it from online sources and dosing it to themselves or their pets, presumably with the assumption of safety and efficacy. In this study, we obtain C(60)-OO from a sample of online vendors, and find marked discrepancies in appearance, impurity profile, concentration, and activity relative to pristine C(60)-OO formulated in-house. We additionally find that pristine C(60)-OO causes no acute toxicity in a rodent model but does form toxic species that can cause significant morbidity and mortality in mice in under 2 weeks when exposed to light levels consistent with ambient light. Intraperitoneal injections of C(60)-OO did not affect the lifespan of CB6F1 female mice. Finally, we conduct a lifespan and health span study in males and females C57BL/6 J mice comparing oral treatment with pristine C(60)-EVOO and EVOO alone versus untreated controls. We failed to observe significant lifespan and health span benefits of C(60)-EVOO or EVOO supplementation compared to untreated controls, both starting the treatment in adult or old age. Our results call into question the biological benefit of C(60)-OO in aging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-020-00292-z.

OBJECTIVES/HYPOTHESIS To analyze the use of highly translatable three-dimensional (3D)-printed auricular scaffolds with and without novel cartilage tissue inserts in a rodent model. STUDY DESIGN Preclinical rodent animal model. METHODS This prospective study assessed a single-stage 3D-printed auricular bioscaffold with or without porcine cartilage tissue inserts in an athymic rodent model. Digital Imaging and Communications in Medicine computed tomography images of a human auricle were segmented to create an external anatomic envelope filled with orthogonally interconnected spherical pores. Scaffolds with and without tissue inset sites were 3D printed by laser sintering bioresorbable polycaprolactone, then implanted subcutaneously in five rats for each group. RESULTS Ten athymic rats were studied to a goal of 24 weeks postoperatively. Precise anatomic similarity and scaffold integrity were maintained in both scaffold conditions throughout experimentation with grossly visible tissue ingrowth and angiogenesis upon explantation. Cartilage-seeded scaffolds had relatively lower rates of nonsurgical site complications compared to unseeded scaffolds with relatively increased surgical site ulceration, though neither met statistical significance. Histology revealed robust soft tissue infiltration and vascularization in both seeded and unseeded scaffolds, and demonstrated impressive maintenance of viable cartilage in cartilage-seeded scaffolds. Radiology confirmed soft tissue infiltration in all scaffolds, and biomechanical modeling suggested amelioration of stress in scaffolds implanted with cartilage. CONCLUSIONS A hybrid approach incorporating cartilage insets into 3D-printed bioscaffolds suggests enhanced clinical and histological outcomes. These data demonstrate the potential to integrate point-of-care tissue engineering techniques into 3D printing to generate alternatives to current reconstructive surgery techniques and avoid the demands of traditional tissue engineering. LEVEL OF EVIDENCE NA Laryngoscope, 131:1008-1015, 2021.

Hordeum vulgare L. (Barley) is an ancient and essential cereal grain crop with the claim that it has the potential to reduce cholesterol level and to lower oxidation activity in the liver.However, it hasn’t been proven scientifically. Hence,this study was conducted to investigate the total phenolic content (TPC), total antioxidant activity (TAC) and liver peroxidation activity of barley aqueous and ethanol extractas well as assess the effect of ethanol extract on cholesterol level of high-fat diet rats. TAC of barley extract was determined by using ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) assay andDPPH (2,2-diphenyl-1-picrylhydrazyl radical) assay. Meanwhile, Total Phenolic Content TPCwas determined by Folin-Ciocalteu assay. Atotal of 15 Sprague Dawley rats were tested for the lowering cholesterol properties in barley and its association with lipid peroxidation product (Melondialdhyhe level) by adding the barley into their daily diet. The result indicated that TAC and TPC value of ethanol barley extract was high. Barley ethanol extracts effectively lowering cholesterol level in Sprague Dawley rats. Meanwhile, the malondialdehyde level in the liver tissue was a significant difference between the high-fat diet group of rats and the high-fat diet group of rats treated with ethanol barley extract. Conclusion, ethanol barley extract possess more phenolic content, antioxidant component and reducing cholesterol level of high-fat diet rats.

Aim Development and characterization of a novel injury-free preclinical model of migraine-like pain allowing mechanistic assessment of both acute and preventive treatments. Methods A “two-hit” hyperalgesic priming strategy was used to induce vulnerability to a normally subthreshold challenge with umbellulone, a transient receptor potential ankyrin 1 (TRPA1) activator, in uninjured female and male C57BL/6 mice. Priming (i.e. the first hit) was induced by three consecutive daily episodes of restraint stress; repeated umbellulone was also evaluated for potential priming effects. Sixteen days after the first restraint stress, mice received inhalational umbellulone (i.e. the second hit) to elicit migraine-like pain. Medications currently used for acute or preventive migraine therapy including propranolol (a beta blocker) and sumatriptan (5HT1B/D agonist), as well as olcegepant, an experimental calcitonin gene related peptide (CGRP) receptor antagonist and nor-Binaltorphimine (nor-BNI), an experimental long-acting kappa opioid receptor (KOR) antagonist, were investigated for their efficacy to block priming and prevent or reverse umbellulone-induced allodynia in primed animals. To assess migraine-like pain, cutaneous allodynia was determined by responses to periorbital or hindpaw probing with von Frey filaments. Results Repeated restraint stress, but not umbellulone exposure, produced transient cutaneous allodynia that resolved within 16 d. Restraint stress produced long-lasting priming that persisted beyond 16 d, as demonstrated by reinstatement of cutaneous allodynia following inhalational umbellulone challenge. Pretreatment with propranolol or nor-BNI prior to restraint stress prevented both transient cutaneous allodynia and priming, demonstrated by a lack of umbellulone-induced cutaneous allodynia. Following establishment of restraint stress priming, olcegepant, but not propranolol or nor-BNI, prevented umbellulone-induced cutaneous allodynia. When administered 1 h after umbellulone, sumatriptan, but not olcegepant, reversed umbellulone-induced cutaneous allodynia in restraint stress-primed rats. Conclusion We have developed a novel injury-free model with translational relevance that can be used to study mechanisms relevant to migraine-like pain and to evaluate novel acute or preventive treatments. Restraint stress priming induced a state of vulnerability to a subthreshold stimulus that has been referred to as “latent sensitization”. The development of latent sensitization could be prevented by blockade of stress pathways with propranolol or with a kappa opioid receptor antagonist. Following establishment of latent sensitization, subthreshold stimulation with umbellulone reinstated cutaneous allodynia, likely from activation of meningeal TRPA1-expressing nociceptors. Accordingly, in restraint stress-primed animals, sumatriptan reversed umbellulone-induced cutaneous allodynia, supporting peripheral sites of action, while propranolol and nor-BNI were not effective. Surprisingly, olcegepant was effective in mice with latent sensitization when given prior to, but not after, umbellulone challenge, suggesting time-dependent contributions of calcitonin gene-related peptide receptor signaling in promoting migraine-like pain in this model. Activation of the calcitonin gene-related peptide receptor participates in initiating, but has a more limited role in maintaining, pain responses, supporting the efficacy of small molecule calcitonin gene-related peptide antagonists as preventive medications. Additionally, the effectiveness of sumatriptan in reversal of established pain thus suggests modulation of additional, non-calcitonin gene-related peptide receptor-mediated nociceptive mechanisms. Kappa opioid receptor antagonists may represent a novel preventive therapy for stress-related migraine.

Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat’s total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.

Objective This study investigated how a chemical-induced analgesia and inflammation could be managed by hot methanol extract of Leea macrophylla (Roxb.) root (LM). Methods Nature of secondary metabolites and the phytochemicals was studied by the established qualitative tests and GC-MS analysis. The analgesic potential was tested by acetic acid-induced writhing model, formalin test and tail immersion model. In contrast, carrageenan and histamine-induced paw edema models were applied to estimate the impact on inflammatogenic agents in Wistar albino rats. Results The LM was found to contain cardiac glycosides, flavonoids, tannins and triterpenoids. A list of about thirty compounds from the GC-MS study of LM has been recorded. The LM significantly (p Conclusion Results demonstrated that L. macrophylla (Roxb.) root extract could be very potential source of therapeutic formulation in pain and inflammation with further clarification.