Acute Effect of Caffeine on the Synthesis of Pro-Inflammatory Cytokines in the Hypothalamus and Choroid Plexus during Endotoxin-Induced Inflammation in a Female Sheep Model.

This study was designed to determine the effect of acute caffeine (CAF) administration, which exerts a broad spectrum of anti-inflammatory activity, on the synthesis of pro-inflammatory cytokines and their receptors in the hypothalamus and choroid plexus (ChP) during acute inflammation caused by the injection of bacterial endotoxin-lipopolysaccharide (LPS). The experiment was performed on 24 female sheep randomly divided into four groups: control; LPS treated (iv.; 400 ng/kg of body mass (bm.

Identification of Reference Genes for Circadian Studies on Brain Microvessels and Choroid Plexus Samples Isolated from Rats.

Delivery of putative compounds of therapeutic value to the brain is limited by brain barriers: the blood-brain barrier located in the endothelium of the brain microvessels (BrMVs) and the blood-cerebrospinal fluid barrier located in the epithelium of the choroid plexus (ChP). Understanding their function and modulation by the circadian clock may enhance the efficacy of brain-targeting therapies. The aim of the present study was to evaluate the stability of 10 reference genes in the BrMV and ChP, isolated from male and female rats at six time points (ZT1, 5, 9, 13, 17, and 21).

Effect of Lipopolysaccharide-Induced Inflammatory Challenge on β-Glucuronidase Activity and the Concentration of Quercetin and Its Metabolites in the Choroid Plexus, Blood Plasma and Cerebrospinal Fluid.

Quercetin-3-glucuronide (Q3GA), the main phase II metabolite of quercetin (Q) in human plasma, is considered to be a more stable form of Q for transport with the bloodstream to tissues, where it can be potentially deconjugated by β-glucuronidase (β-Gluc) to Q aglycone, which easily enters the brain. This study evaluates the effect of lipopolysaccharide (LPS)-induced acute inflammation on β-Gluc gene expression in the choroid plexus (ChP) and its activity in blood plasma, ChP and cerebrospinal fluid (CSF), and the concentration of Q and its phase II metabolites in blood plasma and CSF. Studies were performed on saline- and LPS-treated adult ewes ( = 40) receiving Q3GA intravenously ( = 16) and on primary rat ChP epithelial cells and human ChP epithelial papilloma cells.

Chokeberry anthocyanins and their metabolites ability to cross the blood-cerebrospinal fluid barrier.

The aim of this study was to determine whether anthocyanins and their phase II metabolites permeate the blood-cerebrospinal fluid barrier (B-CSF-B) of sheep and to profile these compounds in sheep biofluids after chokeberry intraruminal administration. Anthocyanins were analyzed using micro-HPLC-MS/MS. After chokeberry administration, anthocyanins were absorbed and occurred in body fluids mainly in the form of methylated, glucuronidated, and sulfated derivatives (in total, 21 derivatives were identified).

Photoperiod Affects Leptin Action on the Choroid Plexus in Ewes Challenged with Lipopolysaccharide-Study on the mRNA Level.

The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (), proinflammatory cytokines (, ), their receptors (, , , , ) and inflammasome components necessary for pro-IL-1β activation (, , ), chemokine (), leptin receptor isoforms (, ) and a suppressor of cytokine signalling () in the ChP of ewes treated or not with lipopolysaccharide (LPS).

Effect of Central Injection of Neostigmine on the Bacterial Endotoxin Induced Suppression of GnRH/LH Secretion in Ewes during the Follicular Phase of the Estrous Cycle.

Induced by a bacterial infection, an immune/inflammatory challenge is a potent negative regulator of the reproduction process in females. The reduction of the synthesis of pro-inflammatory cytokine is considered as an effective strategy in the treatment of inflammatory induced neuroendocrine disorders. Therefore, the effect of direct administration of acetylcholinesterase inhibitor-neostigmine-into the third ventricle of the brain on the gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretions under basal and immune stress conditions was evaluated in this study.

Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation.

The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin-lipopolysaccharide (LPS; 400 ng/kg)-attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed ( < 0.

Plasma and cerebrospinal fluid interleukin-1β during lipopolysaccharide-induced systemic inflammation in ewes implanted or not with slow-release melatonin.

Background: Interleukin-1β (IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid (CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain.

Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle.

The study was designed to test the hypothesis that the inhibition of acetylcholinesterase (AChE) activity at the periphery by Neostigmine (0.5 mg/animal) will be sufficient to prevent inflammatory dependent suppression of the gonadotropin-releasing hormone (GnRH)/luteinising hormone (LH) secretion in ewes in the follicular phase of the estrous cycle, and this effect will be comparable with the systemic AChE inhibitor, Donepezil (2.5 mg/animal).

PCB153 (2,2',4,4',5,5'-hexachlorobiphenyl) differentially affects the VEGF/VEGFR system depending on photoperiod in the ovine choroid plexus.

Ortho-substituted polychlorinated biphenyls (PCBs) preferentially accumulate in the brain and cerebrospinal fluid (CSF) compared with other PCBs. We previously demonstrated in ewes that an identical dose of PCB153, the most environmentally prevalent congener, resulted in a higher plasma concentration during short days (SD: 1200pg/ml) than during long days (LD: 200pg/ml). Moreover, PCB153 treatment only reduced the SD tight junction protein content in the choroid plexus (CP), which was followed by a significant increase of the PCB153 concentration in the CSF.

Quercetin and isorhamnetin aglycones are the main metabolites of dietary quercetin in cerebrospinal fluid.

Scope: Reports on the protective effect of certain foods on brain functions are numerous; however, the permeability of the brain barriers by food components is still hardly recognised. There have been in vitro studies aimed at demonstrating this possibility, but not much is known about this phenomenon in in vivo systems. The objective of the study was to determine the metabolites of dietary quercetin (Q) in urine, blood plasma and cerebrospinal fluid (CSF) after intra-rumen administration of Q rich onion dry skin in an animal model.

Caffeine stimulates in vitro pituitary LH secretion in lipopolysaccharide-treated ewes.

The study was designed to determine the effects of caffeine on luteinizing hormone (LH) secretion and gene expression of caffeine-associated receptors in anterior pituitary (AP) explants obtained from saline- and lipopolysaccharide (LPS)-treated ewes. Animals had been treated with LPS or saline daily for seven days. Three hours after the last injection of LPS/saline, the AP were collected and divided into four explants.

Profile of toll-like receptor mRNA expression in the choroid plexus in adult ewes.

The blood-cerebrospinal fluid barrier (BCSFB) located in the epithelial cells of the choroid plexus (CP) forms the interface between the cerebrospinal fluid (CSF) and pathogen components circulating in the blood. The CP is also implicated in the passage of peripheral immune signals and circulation of immune cells into the central nervous system. Toll-like receptors (TLRs) are patternrecognition receptors that play a crucial role in the recognition of pathogens and triggering of the innate immune response.

Effect of a two-week treatment with a low dose of 2,2'4,4',5,5'-hexachlorobiphenyl (PCB153) on tight junction protein expression in ovine choroid plexus during long and short photoperiods.

Ortho-substituted polychlorinated biphenyls (PCBs) preferentially accumulate in the brain and cerebrospinal fluid (CSF) compared to other PCBs. We previously reported that the same dose of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) induced higher concentrations in the CSF of treated animals compared to controls during short days (SD), while no differences were observed during long days (LD). Similarly, the plasma concentration of PCB153 in treated ewes was higher during SD than LD.

Pattern of expression of vascular endothelial growth factor and its receptors in the ovine choroid plexus during long and short photoperiods.

Vascular endothelial growth factor (VEGF-A) plays an important role in maintaining cerebrospinal fluid (CSF) homeostasis and the function of the choroid plexuses (CPs). The objective of the study was to determine the expression of vascular endothelial growth factor (VEGF-A), tyrosine kinase receptors Flt-1 and KDR and KDR co-receptor neuropilin 1 (NRP-1) in ovine CPs during different photoperiods. CPs were collected from the lateral brain ventricles from ovariectomized, estradiol-treated ewes during long day (LD; 16L:8D, n = 5) and short day (SD; 8L:16D, n = 5) photoperiods.

Photoperiod modulates access of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) to the brain and its effect on gonadotropin and thyroid hormones in adult ewes.

The effects of photoperiod on the cerebrospinal fluid (CSF) concentration of six ortho-substituted polychlorinated biphenyls (PCBs: PCB28, PCB52, PCB101, PCB138, PCB153, and PCB180), the effects of an orally administered low dose of PCB153 (0.3mg/kg, three times a week for three weeks) on PCBs and thyroid hormones (THs) concentrations in the CSF and plasma, and the release of luteinizing hormone (LH) were determined in ovariectomized, estradiol-implanted ewes (2.5 years old) maintained indoors under artificial long day (LD, 16L: 8D) and short day (SD, 8L: 16D) conditions.

Tight junction proteins vary in the choroid plexus of ewes according to photoperiod.

Sheep from temperate latitudes exhibit seasonal variations in many physiological functions such as reproduction, food intake, body weight, and pelage growth. Majority of seasonal changes are controlled by the annual photoperiodic cycle and melatonin secretion. For reproduction, the resulting key event is a modulation of the negative feedback of steroids on gonadotropin secretion.

The choroid plexus--cerebrospinal fluid system: undervaluated pathway of neuroendocrine signaling into the brain.

The cerebrospinal fluid (CSF) is a major part of the extracellular fluid of the central nervous system. The function of the CSF and the tissue that secretes it, the choroid plexus (CP) has traditionally been thought as providing the brain with essential nutrients, removing products of neuronal activity of the central nervous system, and providing mechanical support for the brain's fragile cellular network. More recent studies suggest, however, that the CP and CSF system play a much more active role in the function of the central nervous system being a target, source and pathway for neuroendocrine signaling within the brain.

Luteinising hormone attenuates the vascular response to norepinephrine.

The present study examines the direct effect of luteinising hormone (LH) on the reactivity of the porcine uterine artery to norepinephrine (NE). Three-mm-long arterial segments collected during the luteal phase of the oestrous cycle were mounted in an organ bath for isometric tension recording. After 30 min of equilibration in optimal passive tone, one part of the vessels was treated with 10 ng/ml of LH in PBS (experimental), while a second part of the arterial segments was treated with 10 ng/ml of bovine serum albumin (BSA) in PBS (control).

Luteinizing hormone and prolactin are not retrograde transferred in perihypophyseal vascular complex in ewes.

The objective of the study was to determine whether luteinizing hormone (LH) and prolactin (PRL) can access the brain by way of transfer from the venous blood of the cavernous sinus to the arterial blood supplying the brain and hypophysis. Studies were performed on heads of 22 mature sheep isolated during different phases of the estrous cycle and perfused with autologous blood. We were not able to demonstrate any transfer of LH and PRL in the investigated periods.

Access of dopamine to the median eminence and brain throughout local vascular pathways in sheep.

In female sheep, estradiol-dependent dopaminergic inhibition exerted by the A15 nucleus during long days (LD) results in a blockade of reproductive activity. This effect could involve the GnRH cell bodies or their terminals in the median eminence (ME). However, a vast majority of terminals of the A15 nucleus are located in neurohypophysis and only a few in the ME.

Local vascular pathway for progesterone transfer to the brain after nasal administration in gilts.

In the present study we examined whether local transfer of intranasally administrated tritiated progesterone (3H-P4) would increase its concentration in blood supplying the brain and hypophysis in comparison with other organs. Additionally, the effect of estrous cycle on the P4 transfer was evaluated on isolated gilts' heads. In the first experiment 3H-P4 was instilled into the nasal cavities of anaesthetized, immature pigs (n=10).