Metabolic disorders exacerbate the formation of glial scar after stroke.

Metabolic disorders are risk factors for stroke exacerbating subsequent complications. Rapidly after brain injury, a glial scar forms, preventing excessive inflammation and limiting axonal regeneration. Despite the growing interest in wound healing following brain injury, the formation of a glial scar in the context of metabolic disorders is poorly documented. In this study, we used db/db mice to investigate the impact of metabolic perturbations on brain repair mechanisms, with a focus on glial scarring. First, we confirmed the development of obesity, poor glucose regulation, hyperglycaemia and liver steatosis in these mice. Then, we observed that 3 days after a 30-min middle cerebral artery occlusion (MCAO), db/db mice had larger infarct area compared with their control counterparts. We next investigated reactive gliosis and glial scar formation in db/+ and db/db mice. We demonstrated that astrogliosis and microgliosis were exacerbated 3 days after stroke in db/db mice. Furthermore, we also showed that the synthesis of extracellular matrix (ECM) proteins (i.e., chondroitin sulphate proteoglycan, collagen IV and tenascin C) was increased in db/db mice. Consequently, we demonstrated for the first time that metabolic disorders impair reactive gliosis post-stroke and increase ECM deposition. Given that the damage size is known to influence glial scar, this study now raises the question of the direct impact of hyperglycaemia/obesity on reactive gliosis and glia scar. It paves the way to promote the development of new therapies targeting glial scar formation to improve functional recovery after stroke in the context of metabolic disorders.

Curcumin-Encapsulated Nanomicelles Promote Tissue Regeneration in Zebrafish Eleutheroembryo.

Regenerative medicine is an emerging field of research aiming to understand the wound healing mechanisms and to develop new therapeutic strategies. Nanocarriers are used to improve drug bioavailability, solubility, and therapeutic abilities. In this study, we used for the first time curcumin loaded oligo kappa-carrageenan-graft-polycaprolactone (oligoKC-g-PCL) nanomicelles to investigate their regenerative potential using a model of tail amputation in zebrafish eleutheroembryo. First, we showed that curcumin encapsulated oligoKC-g-PCL spherical micelles had a mean size of 92 ± 32 nm and that micelles were successfully loaded with curcumin. These micelles showed a slow and controlled drug release over 72 h. The toxicity of curcumin nanomicelles was then tested on zebrafish eleutheroembryo based on the survival rate after 24 h. At nontoxic concentration, curcumin nanomicelles improved tail regeneration within 3 days postamputation, compared with empty micelles or curcumin alone. Furthermore, we demonstrated that curcumin nanomicelles increased the recruitment of neutrophils and macrophages 6 h postlesion. Finally, our study highlights the efficiency of oligoKC-g-PCL nanomicelles for encapsulation of hydrophobic molecules such as curcumin. Indeed, our study demonstrates that curcumin nanomicelles can modulate inflammatory reactions in vivo and promote regenerative processes. However, further investigations will be required to better understand the mechanisms sustaining regeneration and to develop new therapeutics.

High Content Imaging and Quantification of Microglia Phagocytosis In Vitro.

Microglia function as the tissue-specific resident macrophages of the nervous system, performing immune and non-immune functions. These functions are critical to development and to maintain homeostasis in the nervous system throughout the lifespan, and during brain injury or disease. One method by which microglia maintain homeostasis is phagocytosis of aberrant proteins, extracellular debris, synapses, or apoptotic cells. Phagocytic function can be changed by environmental or genetic risk factors that affect microglia. These protocols present a rapid and simple in vitro high-content imaging protocol for studying phagocytosis in the murine microglia BV-2 cell line. High-content imaging and analysis enable versatility of the assay, which can be used to test multiple experimental conditions, or as a screening tool. © 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. Basic Protocol 1: Phagocytosis of fluorescently labeled particles Basic Protocol 2: Examining modifications to phagocytosis by test substances Basic Protocol 3: High content imaging and analysis of phagocytic cells.

Distribution of microglia/immune cells in the brain of adult zebrafish in homeostatic and regenerative conditions: Focus on oxidative stress during brain repair.

Microglia are macrophage-like cells exerting determinant roles in neuroinflammatory and oxidative stress processes during brain regeneration. We used zebrafish as a model of brain plasticity and repair. First, by performing L-plastin (Lcp1) immunohistochemistry and using transgenic Tg(mpeg1.1:GFP) or Tg(mpeg1.1:mCherry) fish, we analyzed the distribution of microglia/immune cells in the whole brain. Specific regional differences were evidenced in terms of microglia/immune cell density and morphology (elongated, branched, highly branched, and amoeboid). Taking advantage of Tg(fli:GFP) and Tg(GFAP::GFP) enabling the detection of endothelial cells and neural stem cells (NSCs), we highlighted the association of elongated microglia/immune cells with blood vessels and rounded/amoeboid microglia with NSCs. Second, after telencephalic injury, we showed that L-plastin cells were still abundantly present at 5 days post-lesion (dpl) and were associated with regenerative neurogenesis. Finally, RNA-sequencing analysis from injured telencephalon (5 dpl) confirmed the upregulation of microglia/immune cell markers and highlighted a significant increase of genes involved in oxidative stress (nox2, nrf2a, and gsr). The analysis of antioxidant activities at 5 dpl also revealed an upregulation of superoxide dismutase and persistent H2 O2 generation in the injured telencephalon. Also, microglia/immune cells were shown to be a source of oxidative stress at 5 dpl. Overall, our data provide a better characterization of microglia/immune cell distribution in the healthy zebrafish brain, highlighting some evolutionarily conserved features with mammals. They also emphasize that 5 days after injury, microglia/immune cells are still activated and are associated to a persistent redox imbalance. Together, these data raise the question of the role of oxidative stress in regenerative neurogenesis in zebrafish.

The Antiviral Potential of AdipoRon, an Adiponectin Receptor Agonist, Reveals the Ability of Zika Virus to Deregulate Adiponectin Receptor Expression.

Zika virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique characteristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the absence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce the in vitro infection of A549 epithelial cells, a well-known cell model for flavivirus infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to downregulate adiponectin receptor expression and thereby limit adiponectin signaling.

Distribution of Adiponectin Receptors in the Brain of Adult Mouse: Effect of a Single Dose of the Adiponectin Receptor Agonist, AdipoRON, on Ischemic Stroke.

Adiponectin exhibits pleiotropic effects, including anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective ones. Although some studies have documented brain expression in different rodent models of its receptors, AdipoR1 and AdipoR2, their global distribution remains incomplete. Here, we demonstrated that both AdipoR are widely distributed in the brains of adult mice. Furthermore, by double immunostaining studies, we showed that AdipoR1 and AdipoR2 are mainly expressed in neurons and blood vessels. Then, considering the wide distribution of both receptors and the neuroprotective effects of adiponectin, we tested the therapeutic effect of a single injection of the adiponectin receptor agonist, AdipoRON (5 mg.kg-1), 24 h after stroke in a model of middle cerebral artery occlusion technique (MCAO). Under our experimental conditions, we demonstrated that AdipoRON did not modulate the infarct volume, cell death, neuroinflammatory parameters including microglia activation and oxidative stress. This study suggests that a protocol based on multiple injections of AdipoRON at a higher dose after MCAO could be considered to promote the therapeutic properties of AdipoRON on the brain repair mechanism and recovery.

Genital inflammatory status and the innate immune response to contraceptive initiation.

PROBLEM: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation. METHODS: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors. RESULTS: Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines. CONCLUSION: We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.

ApoA-I Nanoparticles as Curcumin Carriers for Cerebral Endothelial Cells: Improved Cytoprotective Effects against Methylglyoxal.

Methylglyoxal (MGO) is a highly reactive metabolite of glucose present at elevated levels in diabetic patients. Its cytotoxicity is associated with endothelial dysfunction, which plays a role in cardiovascular and cerebrovascular complications. Although curcumin has many therapeutic benefits, these are limited due to its low bioavailability. We aimed to improve the bioavailability of curcumin and evaluate a potential synergistic effect of curcumin and reconstituted high-density lipoprotein (rHDL) nanoparticles (Cur-rHDLs) on MGO-induced cytotoxicity and oxidative stress in murine cerebrovascular endothelial cells (bEnd.3). Cur-rHDL nanoparticles (14.02 ± 0.95 nm) prepared by ultracentrifugation and containing curcumin were quantified by LC-MS/MS. The synergistic effect of cur-rHDL nanoparticles was tested on bEnd.3 cytotoxicity, reactive oxygen species (ROS) production, chromatin condensation, endoplasmic reticulum (ER) stress, and endothelial barrier integrity by impedancemetry. The uptake of curcumin, alone or associated with HDLs, was also assessed by mass spectrometry. Pretreatment with Cur-rHDLs followed by incubation with MGO showed a protective effect on MGO-induced cytotoxicity and chromatin condensation, as well as a strong protective effect on ROS production, endothelial cell barrier integrity, and ER stress. These results suggest that Cur-rHDLs could be used as a potential therapeutic agent to limit MGO-induced dysfunction in cerebrovascular endothelial cells by enhancing the bioavailability and protective effects of curcumin.

Selection and use of reference panels: a case study highlighting current gaps in the materials available for foot and mouth disease.

The World Organisation for Animal Health (OIE) Manual of Diagnostic Tests and Vaccines for Terrestrial Animals describes a diverse array of assays that can be used to detect, characterise and monitor the presence of infectious agents of farmed livestock. These methods have been developed in different laboratories, at different times, and often include tests or kits provided by the commercial sector. Reference panels are essential tools that can be used during assay development and in validation exercises to compare the performance of these varied (and sometimes competing) diagnostic technologies. World Organisation for Animal Health Reference Laboratories already provide approved international standard reagents to help calibrate diagnostic tests for a range of diseases, but there remain important gaps in their availability for comparative purposes and the calibration of test results across different laboratories. Using foot and mouth disease (FMD) as an example, this review highlights four specific areas where new reference reagents are required. These are to: reduce bias in estimates of the diagnostic sensitivity and inter-serotypic specificity of tests used to detect diverse strains of FMD virus (FMDV), provide bio-safe positive controls for new point-of-care test formats that can be deployed outside high containment, harmonise FMDV antigens for post-vaccination serology, and address inter-laboratory differences in serological assays used to measure virus-specific FMD antibody responses. Since there are often limited resources to prepare and distribute these materials, sustainable progress in this arena will only be achievable if there is consensus and coordination of these activities among OIE Reference Laboratories.

Le Manuel des tests de diagnostic et des vaccins pour les animaux terrestres de l'Organisation mondiale de la santé animale (OIE) décrit une vaste panoplie d'essais utilisables pour la détection, la caractérisation et la surveillance des agents pathogènes affectant les animaux d'élevage. Ces méthodes ont été mises au point par des laboratoires différents à diverses périodes et intègrent souvent des tests ou des kits fournis par le secteur privé. Les panels de référence sont des outils essentiels aussi bien lors de la conception d'un essai que lors d'exercices de validation, leur but étant alors de comparer les performances de technologies diagnostiques variées (et parfois concurrentes). Les Laboratoires de référence de l'OIE fournissent des réactifs de référence internationaux validés afin d'aider à calibrer les tests de diagnostic pour un certain nombre de maladies animales ; toutefois, on constate que nombre de ces réactifs ne sont pas disponibles pour la comparaison et le calibrage interlaboratoires des résultats de tests. À partir de l'exemple de la fièvre aphteuse, les auteurs soulignent quatre domaines spécifiques pour lesquels il conviendrait de disposer de nouveaux réactifs de référence. Il s'agit des réactifs nécessaires pour : (1) réduire les biais dans l'estimation de la sensibilité diagnostique et de la spécificité pour différents sérotypes des tests utilisés pour détecter diverses souches du virus de la fièvre aphteuse ; (2) fournir des contrôles positifs sûrs au plan biologique pour les nouveaux formats de tests utilisables sur le lieu d'intervention et non plus dans des laboratoires de confinement à haute sécurité ; (3) harmoniser les antigènes du virus de la fièvre aphteuse pour la sérologie post-vaccinale ; (4) résoudre le problème des différences obtenues entre laboratoires lors d'essais sérologiques visant à mesurer la réponse en anticorps spécifiques du virus de la fièvre aphteuse. Compte tenu des ressources souvent limitées consacrées à la préparation et à la distribution de ces réactifs, des progrès durables ne seront obtenus que s'il existe un consensus en la matière et une coordination de ces activités parmi les Laboratoires de référence de l'OIE.

En el Manual de pruebas de diagnóstico y vacunas para los animales terrestres de la Organización Mundial de Sanidad Animal (OIE) se describe todo un conjunto de ensayos que se pueden emplear para detectar y caracterizar agentes infecciosos del ganado doméstico y hacer así controles sistemáticos de su eventual presencia. Estos métodos, concebidos en distintos laboratorios en distintos momentos, suelen acompañarse de pruebas o estuches analíticos que proporcionan empresas privadas. Los paneles de referencia son una herramienta esencial, que se puede emplear durante la concepción de ensayos y en los procesos de validación para comparar el funcionamiento de estas diferentes técnicas de diagnóstico, que a veces compiten unas con otras. Los laboratorios de referencia de la OIE ya facilitan reactivos de referencia internacional aprobados que ayudan a calibrar las pruebas de diagnóstico de una serie de enfermedades, pero todavía hay importantes carencias por lo que respecta a la posibilidad de procurárselos con fines de comparación y a la calibración de los resultados que obtienen diferentes laboratorios. Sirviéndose del ejemplo de la fiebre aftosa, los autores destacan cuatro aspectos específicos para los que hacen falta nuevos reactivos de referencia. Se trata de los siguientes: reducir el sesgo a la hora de calcular la sensibilidad de diagnóstico y la especificidad interserotípica de las pruebas empleadas para detectar diversas cepas del virus de la fiebre aftosa; proporcionar controles positivos que ofrezcan seguridad biológica para nuevos modalidades de ensayo utilizables en el lugar de consulta, esto es, en condiciones que no sean de alta contención; armonizar los antígenos víricos para la práctica de análisis serológicos tras la vacunación; y solventar las diferencias entre laboratorios por lo que respecta a los ensayos serológicos empleados para medir la respuesta de anticuerpos específicos contra el virus de la fiebre aftosa. Dado que suele haber escasos recursos para preparar y distribuir este tipo de material, solo será posible avanzar duraderamente en la materia si los laboratorios de referencia de la OIE consensúan y coordinan estas actividades.

A one-generation reproductive toxicity study of the mycotoxin ochratoxin A in Fischer rats.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium molds. Grain-based foods account for most human dietary exposures to OTA. OTA is a teratogen, but its reproductive and developmental effects are poorly understood. A one-generation reproductive toxicity study was conducted with groups of 16 male and 16 female Fischer rats exposed to 0, 0.026, 0.064, 0.16, 0.4 or 1.0 mg OTA/kg in diet. Dams exposed to 1.0 mg OTA/kg diet had statistically significant F1 pup losses between implantation and postnatal day (PND 4). Delays in preputial separation (PPS) and vaginal opening (VO) were indicative of delayed puberty in F1 rats. Mild renal lesions in nursing pups indicated that exposure prior to weaning impacted the kidneys. The developing kidney was more susceptible to OTA than the adult kidney. Significant increases in multi-oocyte follicles (MOFs) and proportional changes in resting and growing follicles were observed in F1 female ovaries. Plasma testosterone was reduced in F0 males, and there were negative effects on sperm quality in F0 and F1 male rats. The results confirm that continuous dietary exposure to OTA causes post-implantation fetotoxicity in dams, and renal and reproductive toxicity in their male and female offspring.

Deleterious Effects of Overfeeding on Brain Homeostasis and Plasticity in Adult Zebrafish.

Overweight and obesity are worldwide epidemic health threats. They recently emerged as disruptors of brain homeostasis leading to a wide variety of neurologic disorders. This study aims at developing a fast and easy overfeeding model using zebrafish for investigating the impact of overweight on brain homeostasis. We established a 4-week overfeeding protocol using commercially available dry food in an ad libitum-like feeding. In the diet-induced obesity/overweight (DIO) fish model, weight, size, and body mass index were increased compared with controls. Also, DIO fish displayed hyperglycemia, and had higher levels of advanced glycation end products and oxidative stress (4-hydroxynonenal [4-HNE]) in a peripheral organ (tail). Although overfed fish did not display major blood-brain barrier leakage, they showed an increased cerebral oxidative stress, blunted brain cell proliferation as well as a striking decreased locomotor activity. Interestingly, switching from an overfeeding to a normal diet partially improved peripheral and central disruptions induced by overfeeding in solely 2 weeks. As a conclusion, this study provides a rapid and easy overfeeding model in zebrafish with relevant peripheral and central disruptions. This model could open the way for further investigations to better understand by which mechanisms overfeeding could disturb brain homeostasis. It also reinforces and contrasts with another zebrafish overweight model, showing that the type of the food provided could impair differently brain homeostasis.

Effects of three contraceptive methods on depression and sexual function: An ancillary study of the ECHO randomized trial.

OBJECTIVE: To compare the effects of depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and copper intrauterine device (IUD) on mood and sexual function. METHODS: At the Effective Care Research Unit in South Africa, women already randomized in the ECHO Trial to the three methods were asked to participate in this study. Participants were interviewed at 3 and 12 months after enrollment using the Beck Depression Inventory and Arizona Sexual Experiences Scale, and at 12 months using the WHO-5 Wellbeing Index and the Patient Global Impression scale. RESULTS: A total of 605 women participated. There was little difference in depression at 3 months across the three study groups. Contrary to our hypothesis, at 12 months, depression was lowest among DMPA-IM users (16/167, 9.6%) and highest among IUD users (28/158, 17.7%) (p = 0.032). There was little difference in sexual function at any time-point. More women in the DMPA-IM group felt "very much better" on the PGI scale than in the IUD and LNG implant groups (p = 0.003). CONCLUSION: Depression may be less likely with DMPA-IM than with the other methods 1 year after initiation. Major differences in sexual functioning are unlikely. Unhappiness related to not using DMPA-IM, the most popular method in our setting, may have skewed results. TRIAL REGISTRATION NUMBER: PACTR201706001651380.

Clinical and dosimetric impact of totally implantable venous access devices in radiotherapy of supra diaphragmatic Hodgkin Lymphoma.

PURPOSE: To evaluate attenuation of the totally implantable vascular access device (TIVAD) and assess its clinical and dosimetric impact on radiotherapy (RT) of lymphoma patients. MATERIALS AND METHODS: The first part of the study consisted of an in vitro approach by irradiating the TIVAD with different electron and photon energies. The attenuation data measured were compared with data calculated by our treatment planning system. All patients treated by radiotherapy for Hodgkin's lymphoma with their TIVAD in the target volume were then reviewed to assess the clinical outcome and dosimetric comparison using different plan metrics. All patients were treated by 3D conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy delivered by Helical Tomotherapy (HT). RESULTS: Nineteen patients treated for stage I-III HL were studied. Seven patients were treated exclusively on the side of TIVAD and 12 were treated bilaterally. Median prescription dose was 30Gy. No significant clinical or dosimetric differences were observed between the side of the TIVAD and the contralateral side in patients treated bilaterally. HT resulted in a significantly higher conformity index (P<0.0022) and a significantly lower healthy tissue coverage (P=0.0008) than 3DCRT. The observed attenuation was 79% for 6 MeV, 59% for 9 MeV, and 46% for 12 MeV for electrons and 9% for 4 MV, 8% for 6 MV, 5% for 10 MV and 15 MV and 3% for 20 MV for X photons. CONCLUSION: TIVADs induce significant beam attenuation when using electrons, which can be overcome by using high-energy photons or by creating an exclusion zone in when HT is used.

Impaired brain homeostasis and neurogenesis in diet-induced overweight zebrafish: a preventive role from A. borbonica extract.

Overweight and obesity are worldwide health concerns leading to many physiological disorders. Recent data highlighted their deleterious effects on brain homeostasis and plasticity, but the mechanisms underlying such disruptions are still not well understood. In this study, we developed and characterized a fast and reliable diet-induced overweight (DIO) model in zebrafish, for (1) studying the effects of overfeeding on brain homeostasis and for (2) testing different preventive and/or therapeutic strategies. By overfeeding zebrafish for 4 weeks, we report the disruption of many metabolic parameters reproducing human overweight features including increased body weight, body mass index, fasting blood glucose levels and liver steatosis. Furthermore, DIO fish displayed blood-brain barrier leakage, cerebral oxidative stress, neuroinflammation and decreased neurogenesis. Finally, we investigated the preventive beneficial effects of A. borbonica, an endogenous plant from Reunion Island. Overnight treatment with A. borbonica aqueous extract during the 4 weeks of overfeeding limited some detrimental central effects of DIO. In conclusion, we established a relevant DIO model in zebrafish demonstrating that overfeeding impairs peripheral and central homeostasis. This work also highlights the preventive protective effects of A. borbonica aqueous extracts in DIO, and opens a way to easily screen drugs aiming at limiting overweight and associated neurological disorders.

Food toxins and the Caribbean Parkinson plus types.

In the 90's, clinico pathological studies have considerably improved the diagnosis of specific and rare neurodegenerative diseases. After a training in Parkinsons' disease in Paris, the author moved to French West Indies (Guadeloupe) and observed a high incidence of atypical parkinsonism with dementia, unresponsive to levodopa. Similar features were observed in Martinique. An environmental origin has been suspected with the exposure to toxins of annonaceae leaves and seeds. The candidate toxins are acetogenins acting as mitochondrial poison. This was demonstrated in neuronal cell cultures, and in animals. However, the agency for food security did not conclude that Annonaceae should not be used for herbal (medicinal) tea, even if the population is now aware about the possible risk of parkinsonism after exposure to annonaceae acetogenins.

Enhanced effects of curcumin encapsulated in polycaprolactone-grafted oligocarrageenan nanomicelles, a novel nanoparticle drug delivery system.

One of the most effective strategies to enhance the bioavailability and the therapeutic effect of hydrophobic drugs is the use of nanocarriers. We have used κ-carrageenan extracted from Kappaphycus alvarezii to produce oligocarrageenan via an enzymatic degradation process. Polycaprolactone (PCL) chains were grafted onto the oligocarrageenans using a protection/deprotection technique yielding polycaprolactone-grafted oligocarrageenan. The resulting amphiphilic copolymers formed spherical nanomicelles with a mean size of 187 ± 21 nm. Hydrophobic drugs such as curcumin were efficiently encapsulated in the micelles and released within 24-72 h in solution. The micelles were non-cytotoxic and facilitated the uptake of curcumin by endothelial EA-hy926 cells. They also increased the anti-inflammatory effect of curcumin in TNF-alpha-induced inflammation experiments. Finally, in vivo experiments supported a lack of toxicity in zebrafish and thus the potential use of polycaprolactone-grafted oligocarrageenan to improve the delivery of hydrophobic compounds to different organs, including liver, lung and brain as shown in mice.

Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair.

Adiponectin and its receptors (adipor) have been initially characterized for their role in lipid and glucose metabolism. More recently, adiponectin signaling was shown to display anti-inflammatory effects and to participate in brain homeostasis and neuroprotection. In this study, we investigated adipor gene expression and its regulation under inflammatory conditions in two complementary models: mouse and zebrafish. We demonstrate that adipor1a, adipor1b, and adipor2 are widely distributed throughout the brain of adult fish, in neurons and also in radial glia, behaving as neural stem cells. We also show that telencephalic injury results in a decrease in adipor gene expression, inhibited by an anti-inflammatory treatment (Dexamethasone). Interestingly, adiponectin injection after brain injury led to a consistent decrease (a) in the recruitment of microglial cells at the lesioned site and (b) in the proliferation of neural progenitors, arguing for a neuroprotective role of adiponectin. In a comparative approach, we investigate Adipor1 and Adipor2 gene distribution in the brain of mice and demonstrated their expression in regions shared with fish including neurogenic regions. We also document Adipor gene expression in mice after middle cerebral artery occlusion and lipopolysaccharide injection. In contrast to zebrafish, these inflammatory stimuli do no impact cerebral adiponectin receptor gene expression in mouse. This work provides new insights regarding adipor expression in the brain of fish, and demonstrates evolutionary conserved distribution of adipor with mouse. This is the first report of adipor expression in adult neural stem cells of fish, suggesting a potential role of adiponectin signaling during vertebrate neurogenesis. It also suggests a potential contribution of inflammation in the regulation of adipor in fish.

Short communication: Relationships among plasma and milk vitamin B12, plasma free fatty acids, and blood ß-hydroxybutyrate concentrations in early lactation dairy cows.

This study was undertaken to evaluate the relationship between plasma and milk concentrations of vitamin B12 as well as the relationship between plasma or milk concentrations of vitamin B12 and plasma concentration of free fatty acids (FFA) or blood concentration of ß-hydroxybutyrate (BHB) of early lactating Ayrshire (AY) and Holstein (HO) cows. A total of 44 dairy herds (7 AY and 37 HO herds) and 62 AY (21 in first, 19 in second, and 22 in third and more lactations) and 228 HO (51 in first, 74 in second, and 103 in third and more lactation) cows between 3 and 40 d in milk were involved in the study. Hand-stripped milk samples and blood samples were taken 6 h after the morning milking. Milk and plasma samples were analyzed for vitamin B12 concentration and plasma samples were analyzed for FFA concentration. A handheld device was used for blood BHB concentration determination. Thresholds for elevated plasma FFA concentration and hyperketonemia were set at ≥0.70 and ≥1.2 mmol/L, respectively. Vitamin B12 concentration in milk of AY primiparous cows [2,557 (1,995-3,276) pg/mL] was lower than in milk from HO primiparous cows [3,876 (3,356-4,478) pg/mL], whereas no difference was observed among other parities and breeds. Regardless of breeds, plasma concentration of vitamin B12 of first and second parities was lower than plasma concentration of third and more lactation cows. Milk vitamin B12 concentration was positively correlated with plasma vitamin B12 concentration, but the relationship was stronger for AY (ρ averaging 0.63) than for HO cows (ρ averaging 0.36). For AY and HO breeds, a significant relationship between milk or plasma vitamin B12 concentrations and plasma FFA concentration (ρ between 0.29 and 0.59) was observed. Moreover, cows with elevated plasma FFA concentration had greater milk and plasma vitamin B12 concentrations than cows with normal plasma FFA concentration. No relationship between vitamin B12 concentration in milk or plasma and blood BHB concentration and hyperketonemia was noted. In summary, milk is not well correlated with plasma vitamin B12 concentration for HO. It could be hypothesized that elevated plasma concentration of FFA could have a negative effect on the use of vitamin B12 by cow cells, which increases the concentration of the vitamin in plasma and its secretion in milk.

Effect of feeding system and grain source on lactation characteristics and milk components in dairy cattle.

The objective of this study was to examine the effect of feeding systems [component and total mixed rations (TMR)] and dietary grain sources (barley, commercial concentrate, corn grain, and high-moisture corn) on lactation characteristics and milk composition. A total of 852,242 test-day records, information on animal characteristics, feed composition, and feeding systems from 104,129 Holstein cows in 4,319 herds covering a period of 5 yr were obtained from Quebec's Dairy Herd Improvement Association (Valacta). We performed descriptive statistics and graphical representations of the data for each type of feeding system and grain source by parity (1 to 3). The milk records were binned in 15-d in milk blocks. Mixed models using a combination of forward and backward stepwise selections were developed to predict milk and milk component yields. The TMR-fed cows had greater yield of milk, fat, protein, and lactose and lower milk urea N (MUN) concentration than component-fed cows at all parities. Cows fed a TMR had higher peak milk yields and greater persistency after peak lactation compared with component-fed cows. In addition, greater yields of milk fat and protein from peak to mid-lactation were found in TMR- versus component-fed cows. In general, greater milk fat and protein yields as well as lower MUN concentration were observed in cows fed corn grain or high-moisture corn compared with barley or commercial concentrate, but parity influenced these relationships. The feeding system by day in milk blocks interaction was significant in models of milk and components yields for all parities, but only for second-lactation cows for MUN concentration. This means that effect of TMR and component feeding differs with stage of lactation. In conclusion, feeding TMR and corn-based diets are associated with greater yield of milk and milk components under commercial conditions.