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.
Studies performed on a variety of species (pigs, sheep, rabbits, rats) indicate the existence of a local transfer system of substances between blood vessels located at the base of the cranium (the cavernous sinus - carotid artery vascular complex). This local transfer allows for some hormones synthesized in the brain and hypophysis, as well as biologically active substances absorbed from the nasal mucosa, and drained to the cavernous sinus to reach the brain vasculature in a concentration locally higher than that measured in systemic circulation. The present paper gives an overview of: 1. the major anatomical structure engaged in the transfer, 2. experimental evidence for substance transfer in the vascular complex, 3. factors affecting the transfer and 4. possible physiological importance.
Interaction between the immune system and pineal gland seems to be bidirectional. The feedback effect of an inflammatory response on the pineal gland is poorly understood, however. This study was performed to analyse the pattern of mRNA expression of receptors belonging to the Toll-like receptors (TLR) family in the pineal gland of ewes under different photoperiod conditions. TLRs are involved in the initiation of the innate immune response because they recognize different pathogen-associated molecular patterns (PAMPs). The experiment was carried out on adult Blackface ewes during long-day (LD, 18:6, June; n = 6) and short-day (SD, 6:18, December; n = 6) periods. The animals were euthanized 5 h after sunset (at 21:00 during SD and 2:00 during LD). The mean concentration of circulating melatonin in the last hour of the experiment was higher (P < 0.05) during the SD (270 ± 15 pg· ml–1) compared with the LD period (108 ± 5 pg · ml–1). The expression of genes encoding each TLR was differentiated. TLR3 had the highest mRNA expression, followed by TLRs 1, 2, 5, 7, 9, 8, 4, 10 and 6. Gene expression also varied for each TLR and was influenced by the photoperiod and/or melatonin. The gene whose expression varied the most was TLR10 (coefficient of variation, 42%) during the LD period, but during the SD period, the expression of TLR6 varied most (coefficient of variation, 42%). The study showed that the cells of the pineal gland express transcripts for all ten members of the TLR family, therefore, the functioning of this gland may be affected by number of PAMPs recognized by these receptors.
Thyroid hormones (THs) are obligatory for transition from breeding season to anestrus in sheep. In this process, THs act during a very limited time of the year and primarily within the brain. In ewes chronically equipped for sampling cerebrospinal fluid (CSF) from the third ventricle, we have characterized the concentrations of total and free thyroxine (T4), triiodothyronine (T3), and total reverse T3 (rT3) in the CSF during breeding season, anestrus and during a critical period required for transition to anestrus (December-March). The total T4, T3, rT3 and free T3 average concentrations (± SEM) in CSF were 1.5 ± 0.07 ng/ml, 14.5 ± 1.2 pg/ml, 43 ± 7.4 pg/ml, and 0.6 ± 0.05 pg/ml, respectively, and all were significantly lower (p < 0.001) than in blood plasma except free T4 (12.6 ± 1.1 pg/ml), which was similar to that in plasma. There was a seasonal trend (p < 0.05) in the concentration of total T3 (highest in December) and free T4 (highest in November) in the CSF that does not follow that in blood plasma. During the period of transition to anestrus the CSF total T3/TT4 molar ratio and free T3/ T4 ratio were significantly lower (p < 0.05 and p < 0.01, respectively) than in blood plasma, while the total rT3/T4 ratio was significantly higher (p < 0.01) at the end of this period (March). Additionally, the CSF total rT3 concentrations were also significantly correlated with the CSF total T4 levels (r = 0.57; p < 0.05). In conclusion, the CSF in sheep may serve as a considerable source of thyroid hormones for neuroendocrine events. The lack of significant changes in THs concentrations in the CSF during the period of transition to anestrus indicate that neither seasonal changes of THs circulating in the blood plasma nor THs circulating in the CSF actively drive the transition to anestrus.
The contractile effects of PGF₂α (3 × 10⁻⁶ to 10⁻⁴ M) and PGE₂ (10⁻⁷ to 10⁻⁵ M) were examined on isolated branches of ovarian artery (OA) and extramyometrial branches of uterine artery (UA) collected from pigs in the luteal (day 10-12) and follicular phase (day 17-20) of the estrous cycle, and during early pregnancy (day 10-12). Strong contraction was demonstrated in both arteries during all investigated periods in response to PGF2α, which was significantly higher (P < 0.01) than to PGE₂, being negligible in the follicular phase. In UA, the effective dose of PGF₂α (ED50) amounted 7.9 × 10⁻⁶ M and 6.3 × 10⁻⁶ M in the luteal and follicular phase, and 5.0 × 10⁻⁶ M in early pregnancy. ED50 for PGE₂ reached 5.0 × 10⁻⁷ M in the luteal phase, and 4.1 × 10⁻⁷ M in early pregnancy. For both prostaglandins, the contraction was much stronger (P < 0.01) in OA than in UA branches. In OA, the ED50 for PGF₂α was 1.2 × 10⁻⁵ M in the luteal phase and was significantly higher (P < 0.05) than in the follicular phase (3.1 × 10⁻⁶ M) and early pregnancy (2.7 × 10⁻⁶ M). ED50 for PGE2 amounted 7.3 × 10⁻⁷ M in the luteal phase and 1.7 × 10⁻⁷ M in early pregnancy. Studies showed the influence of the estrous cycle and early pregnancy on OA branches sensitivity to the contractile effect of PGF₂α and the lack of this effect on UA branches, and the influence of the estrous cycle on UA and OA branch contraction in response to PGE2.
Local counter current transfer of substances between venous and arterial vessels has been found in the perihypophyseal vascular complex after administration into the supraorbital vein. The present experiments investigate whether similar transfer could be found after nasal administration of testosterone. Experiments were conducted on the model of isolated pig's head perfused with autologous blood through one carotid artery. Tritium labelled testosterone was infused onto the nasal mucous. Radioactivity was measured in blood samples collected from the contralateral carotid artery (indicator of transfer), in the venous effluent from the jugular veins (indicator of absorption), and in tissue samples from the olfactory bulb, olfactory triangle, hypothalamus, mammillary body, cortex, pons, cerebellum, neurohypophysis, adenohypophysis, pia vessels and perihypophyseal vascular complex. The absorption was 11.4 ±4.6 per cent (mean ± SEM) and 0.4 ±0.3 per cent of the instilled testosterone was transferred during the 25 min collection period. The uptake of radioactivity was seen in many of the brain tissue samples representing the brain, pituitary, pia vessels and cavernous sinus - carotid rete complex, although a clear pattern was not seen. Nasally administered drugs may thus reach the brain in a relatively higher concentration than it reaches the rest of the body. This makes targeted treatment of the brain a distinct possibility. Additionally, the treatment will decrease the first-passage metabolism in the liver.
The aim of study was to evaluate the effect of oral Yersinia enterocolitica infection on the course and duration of pregnancy, litter parameters, and endocrine milieu in sows depending on the phase of pregnancy at the moment of infection. The studies were performed on 12 pregnant sows, divided into four groups (n=3) and infected per os on the first (33 d of pregnancy -dp), second (54 dp), and third (89 dp) trimester of pregnancy with the pathogenic Y. enterocolitica strain isolated from palatine tonsil of aborted swine foetus. The control group remained uninfected. The most deviations from physiological and clinical norms exhibited sows infected in the third trimester of pregnancy. In this group deliveries happened the latest (118 dp), the number of stillborn piglets was the highest (14.5%), and mean piglet body weight was the lowest (1.1 kg). In all sows from the group, vaginal purulent effluent occurred and lasted about two weeks after parturition. The least numerous litters were observed in group infected in the first trimester (11.1). Haematological examinations revealed only slight leukocytosis in all infected groups during 2 weeks post infection. No significant abnormalities in the concentration of the examined hormones were found but Y. enterocolitica infection could influence P₄ and E₁-S levels of pregnant animals and that influence was dependent on the pregnancy period when the infection happened.
Ortho-substituted polychlorinated biphenyl (PCB) congeners, which constitute a large part of PCB residues found in the environment and in animal tissues, are known to exert potent vascular effects and can activate endothelial cells in the periphery and in the brain. The choroid plexus (CP) is responsible for cerebrospinal fluid (CSF) production and its epithelial cell layer is responsible for structure and functions of the blood-CSF barrier. The aims of this study were: 1) to investigate if environmentally relevant doses of PCB153 and similar doses of PCB104 caused changes in the expression of vascular endothelial growth factor (VEGF) - receptor system, which maintains CP function, and 2) to determine the level of both congeners in blood plasma after their oral administration. Studies of both congeners were performed on ovariectomized ewes treated per os with low doses (0.1 mg/kg, three times a week for two weeks) of PCB153 (n=4) or PCB104 (n=4) and vehicle (control, n=4). The effects of PCB153 and PCB104 treatment on mRNA expression of two isoforms of VEGF (VEGF120 and VEGF164) and their receptors Flt-1 and KDR were determined using real-time PCR. Plasma concentration of PCBs was measured using high resolution chromatography/tandem mass spectrometry (HRGC/MS-MS). We observed that neither PCB153 nor PCB104 significantly altered the mRNA of the VEGF-receptor system in the CP. In PCB treated animals plasma concentration of PCB153 (1.425 ± 0.16 ng/g of dry mass, DM) was about 150 times higher than PCB104 (0.009 ± 0.007ng/g DM). In control animals the PCB153 level was 0.14 ± 0.031 ng/g DM, while the PCB104 level was below detection level. This indicates that increase in plasma PCB153 concentration to levels similar to those reported in humans and of PCB104 concentration to levels 100 times higher than those found in human plasma did not affect the VEGF-receptor system in the CP in adult ewes. The significantly lower increase of PCB104 than PCB153 concentration in blood after oral administration suggests different absorption of both congeners from the digestive tract.