Expression of Toll-Like Receptors in the Animal Model of Bladder Outlet Obstruction.

INTRODUCTION: Bladder outlet obstruction (BOO) occurs in more than 20 percent of the adult population and may lead to changes in the structure and function of the bladder. The main objective of the study was to evaluate the expression of Toll-like receptor 4 (TLR 4) and Toll-like receptor 9 (TLR 9) in the animal model of BOO as potential triggers of the inflammation phase in the bladder. In addition, the modulating effect of alpha-1 adrenergic antagonist (tamsulosin) on TLR 4 and TLR 9 expression and inflammatory markers was assessed. Material and Methods. Thirty-two male, 9-week-old Sprague Dawley rats were randomly divided into 4 groups: SOP-sham-operated rats with a placebo (water); SOB-sham-operated rats with an alpha-1 adrenergic antagonist; BOOP-rats with BOO and a placebo; and BOOB-rats with BOO and an alpha-1 adrenergic antagonist. The rats were given a placebo or alpha-1 adrenergic antagonist for 15 days. Next, urine and the bladder were collected from the rats for histopathological and biochemical study. RESULTS: Histopathological analysis showed chronic inflammation without acute inflammation in the bladder. TLR 4 showed positive cytoplasmic reactivity in the urothelium and the smooth muscles of the bladder. TLR 9 showed positive cytoplasmic reactivity only in the urothelium. BOO caused an increase in TLR 4 and TLR 9 expression. Furthermore, treatment with an alpha-1 adrenergic antagonist had no significant effect on TLR 4 and TLR 9 expression in rats with BOO. BOO caused a significant increase in urine concentration of interleukin 6 (IL-6), while alpha-1 antagonist reduced the urine concentration of IL-6 and the concentration of interleukin 18 (IL-18). CONCLUSIONS: The results suggest the participation of TLR 4 and TLR 9 receptors in the induction of inflammation in the bladder, which is the first phase in the development of pathophysiological changes in BOO.

A rat model to study maternal depression during pregnancy and postpartum periods, its comorbidity with cardiovascular diseases and neurodevelopmental impact in the offspring.

This study aimed to develop an animal model of human depression during pregnancy and lactation to examine the effect of maternal, perinatal depression on offspring development. Maternal depression during pregnancy affects up to 20% of women and is a risk factor for both the developmental and long-term health issues. It is often comorbid with the cardiovascular disease (CVD) that affects the uteroplacental circulation and impacts offspring development. More than half of the expecting mothers with depression use antidepressants that cross the placenta and may interfere with the neurodevelopmental programming. Thus, depressed pregnant mothers face a difficult choice whether "to use or not to use" antidepressant therapy, since both untreated depression and antenatal antidepressant exposure present increased risks of neurodevelopmental pathologies. The ongoing clinical debate presents inconclusive data, while the existing animal models of maternal depression do not include early gestational periods, and, do not monitor depressive-like behavior nor address the cardiovascular abnormalities. The presented model includes pregestational depressive behavior extending into pregnancy and lactation, periods that have not been previously examined. Rat dams exposed to pre-gestational chronic mild stress (CMS) developed a sustained decrease in self-grooming behavior, correlated with hormonal, behavioral, and cardiac changes persisting through the postpartum period. Preliminary data indicate neurodevelopmental delays, behavioral and cardiac abnormalities, and altered levels of both the brain and the heart markers in the offspring of stressed dams. Furthermore, the preliminary data predict that maternal pregnancy during the perinatal period is likely to impact the neurodevelopmental process in a sex-dependent manner. Thus the presented here model (PG-LAC CMS) fulfills both the face and the construct validity criteria for maternal stress-induced depression during pregnancy and postpartum that may facilitate further studies of the relative risks of untreated vs. antidepressant-treated maternal depression during pregnancy to the mother and her offspring.

Effect of dimethyl fumarate on heme oxygenase-1 expression in experimental allergic encephalomyelitis in rats.

Multiple sclerosis (MS) is an autoimmunological disease leading to neurodegeneration. The etiology of the disease remains unknown, which strongly impedes the development of effective therapy. Most MS treatments focus on modulating the activity of the immune system. Dimethyl fumarate (DMF) exerts a broad spectrum of action, such as modulating immune cell differentiation towards anti-inflammatory subtypes, influencing cytokine production, regulating immune cell migration into the central nervous system, and activating intracellular antioxidant mechanisms. It is well established that activation of the nuclear factor E2 (Nrf2)-dependent pathway, leading to expression of the second-phase antioxidant enzymes, is influenced by DMF. In our experiments we used female Lewis rats in an animal model of MS - experimental allergic encephalomyelitis (EAE). The rats were fed with dimethyl fumarate to test the expression of heme oxygenase-1 (HO-1), one of the second-phase antioxidant enzymes, at specific time points of the symptomatic phases of the disease: on the first day of the occurrence of clinical symptoms (10th day post immunization, DPI); at the peak of clinical symptoms (14th DPI); and at the end of the relapse (21st DPI). The results showed that HO-1 expression, at both the mRNA and protein level, is influenced by DMF administration only at the very beginning of the symptomatic phase of EAE, and not at the peak of clinical symptoms, nor at the end of the relapse. This indicates that the regulation of the Nrf2-dependent antioxidant pathway by DMF occurs at a certain time interval (early EAE/MS) and strongly underlines the importance of the earliest introduction of the therapy to the patient. .