[Impairments of rats' behavioral reactions, concentration of corticosterone and expression of cytokine's gene under experimental postviral fatigue].

The aim of the main research was investigated of interaction of neural, endocrine and immune systems under experimental postviral fatigue, behavioral reactions, level of corticosterone, changes of IL-3 and IL-10 gene expression in rats' hypothalamus and INF-α in hypothalamus and spleen were analyzed. It has been shown the decrease of physical activity, increasing of corticosterone's level and gene expression of cytokines after injection of Poly I:C as a model of postviral fatigue. After remedication of Poly I:C increasing of physical activity was shown.

Hypolocomotive behaviour associated with increased microglia in a prenatal immune activation model with relevance to schizophrenia.

Over the past decade a neurodevelopmental animal model with high validity for schizophrenia has been developed based on the environmental risk factor known as maternal immune activation (MIA). The immunological basis of this model, together with extensive data from clinical and preclinical context, suggests the involvement of an aberrant neuro-immune system in the pathophysiology of schizophrenia. The goal of this study was to examine microglia activation in adult behaviourally phenotyped MIA offspring. MIA was induced in pregnant rats using viral mimetic Poly I:C at gestational day 15. Adult offspring were behaviourally phenotyped at postnatal days (PND) 56, 90 and 180 through the evaluation of prepulse inhibition (PPI) of the acoustic startle and spontaneous locomotion. Finally, the presence of activated microglia in brain regions associated with schizophrenia was evaluated using post-mortem immunohistochemistry against OX-42 (CD11b) and ED-1 (CD68). Although a deficit in PPI could not be replicated despite the high number of animals tested, we found an overall decrease in basal startle response and spontaneous locomotion in offspring born to Poly I:C- compared to saline-treated dams, accompanied by increased microglial density with characteristics of non-reactive activation in the chronic stage of the model. These findings provide additional evidence for a role played by microglial activation in schizophrenia-related pathology in general and psychomotor slowing in particular, and warrant extensive research on the underlying mechanism in order to establish new drug targets for the treatment of schizophrenia patients with an inflammatory component.

Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and immunohistological study in Wistar rats.

Cerebral stroke is the third largest cause of death and the severe leading cause of disability, thus have astronomical financial and social burden worldwide. Accumulated evidence suggests that ROS can be scavenged through utilizing natural antioxidant compounds present in foods and medicinal plants. In this study, we examined whether silymarin, an antioxidant, present in the milk of thistle can prevent or slowdown neuronal injury in focal cerebral ischemia. Male Wistar rats were pre-treated with silymarin (200mg/kg body weight, dissolved in 0.3 % sodium carboxymethyl cellulose, once orally) for 15 days. On day 16, they underwent a transient 2h suture-occlusion of the middle cerebral artery followed by 22 h of reperfusion. Rats were tested for neurobehavioral activity after 22 h reperfusion. Silymarin was found to be successful in upregulating the antioxidant status and lowering the apoptotic responses, and functional recovery returned close to the baseline. This study revealed that silymarin, a naturally occurring flavone from the milk thistle (Silybum marianum), may be helpful in slowing down the progression of neurodegeneration in focal cerebral ischemia. These results suggest that the neuroprotective potential of silymarin is mediated through its anti-oxidative and anti-apoptotic properties.

Evaluation of the efficacy and safety of olopatadine and fexofenadine compared with placebo in Japanese cedar pollinosis using an environmental exposure unit.

BACKGROUND: Second-generation oral H1-antihistamines have become a mainstay of treatment for the symptoms of seasonal allergic rhinitis; however, the effect of olopatadine has not been widely reported to date. OBJECTIVES: To evaluate the efficacy of 2 oral H1-antihistamines, olopatadine and fexofenadine, in the treatment of the nasal symptoms of Japanese cedar pollinosis and their possible side effects. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study conducted in an environmental exposure unit (EEU). Twenty volunteers suffering from Japanese cedar pollinosis were randomly divided into 3 groups and exposed to cedar pollen in the EEU with oral administration of olopatadine hydrochloride (5 mg), fexofenadine hydrochloride (60 mg), or placebo 1 hour prior to pollen exposure. Nasal symptoms, activity impairment, and subjective sleepiness were self-assessed during the study period. Attention was measured using the digit cancellation test. The trial was repeated after 4 and 7 weeks. RESULTS: Compared with placebo, olopatadine significantly improved nasal symptoms and activity impairment during pollen exposure (P < .05). There was no significant relief of nasal discharge or nasal congestion with fexofenadine throughout the 5-hour exposure to cedar pollen. Furthermore, olopatadine significantly reduced nasal congestion during the first 2 hours, as well as sneezing and nasal discharge 4 hours after admission to the EEU compared with fexofenadine (P < .05). There was no significant difference in the effect on subjective sleepiness among the 3 groups, and all 3 agents had little effect on attention. CONCLUSIONS: These findings suggest that olopatadine is more effective than placebo and fexofenadine in improving nasal symptoms of Japanese cedar pollinosis.

Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection.

The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups. Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.

Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior.

Proinflammatory cytokines induce both sickness behavior and depression, but their respective neurobiological correlates are still poorly understood. The aim of the present study was therefore to identify in mice the neural substrates of sickness and depressive-like behavior induced by lipopolysaccharide (LPS, 830 microg/kg, intraperitoneal). LPS-induced depressive-like behavior was dissociated from LPS-induced sickness by testing mice either at 6 h (at which time sickness was expected to be maximal) or at 24 h post-LPS (at which time sickness was expected to be minimal and not to bias the measurement of depressive-like behavior). Concurrently, the expression of acute and chronic cellular reactivity markers (c-Fos and FosB/DeltaFosB, respectively) was mapped by immunohistochemistry at these two time points. In comparison to saline, LPS decreased motor activity in a new cage at 6 h but not at 24 h. In contrast, the duration of immobility in the tail suspension test was increased at both 6 and 24 h. This dissociation between decreased motor activity and depressive-like behavior was confirmed at 24 h post-LPS in the forced swim test. LPS also decreased sucrose consumption at 24 and 48 h, despite normal food and water consumption by that time. At 24 h post-LPS, LPS-induced depressive-like behavior was associated with a delayed cellular activity (as assessed by FosB/DeltaFosB immunostaining) in specific brain structures, particularly within the extended amygdala, hippocampus and hypothalamus, whereas c-Fos labeling was markedly decreased by that time in all the brain areas at 6 h post-LPS. These results provide the first evidence in favor of a functional dissociation between the brain structures that underlie cytokine-induced sickness behavior and cytokine-induced depressive-like behavior, and provide important cues about the neuroanatomical brain circuits through which cytokines could have an impact on affect.

Long term alterations in neuroimmune responses of female rats after neonatal exposure to lipopolysaccharide.

Male and female rats display significant gender-associated differences in their responses to an immune challenge, and gender-specific alterations in many aspects of physiology are seen after a variety of interventions during the neonatal period. It is well-established that neonatal exposure to an immune challenge can alter centrally mediated inflammatory responses in adult male rats and yet little is known about female responses after a similar challenge. We therefore asked if neonatal exposure to lipopolysaccharide (LPS) would alter febrile and hypothalamic cyclooxygenase (COX)-2 responses to an adult immune challenge in female rats. Female Sprague-Dawley rats were administered a single injection of the bacterial endotoxin LPS at postnatal day 14 and were examined as adults for febrile, COX-2 and activity changes to LPS, as well as responses to interleukin (IL)-1beta. Adult female rat responses were similar to those we have seen previously for the males in that febrile and hypothalamic COX-2 responses to adult LPS were attenuated in neonatally LPS-treated animals. Responses to adult IL-1beta were unaffected. Interestingly, females did not display the elevated basal hypothalamic COX-2 that was previously seen in males. Thus we demonstrate that, like in the males, neonatal exposure to LPS has a powerful effect on adult responses to further LPS challenge in the female rats.

Relationships among the behavioral, noradrenergic, and pituitary-adrenal responses to interleukin-1 and the effects of indomethacin.

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.

Differential response of lymphocytes and neutrophils to high intensity physical activity and to vitamin C diet supplementation.

We have determined the effects of chronic vitamin C intake on neutrophil and lymphocyte antioxidant defences during the acute phase immune response induced by intense exercise. Blood samples were taken from 16 voluntary athletes in basal conditions, both immediately after and 1 h after a duathlon competition. Sportsmen's nutrient intakes were determined before the competition. After determining the basal plasmatic ascorbate levels, the results were analysed taking into account the vitamin C intake and their plasmatic levels. Two groups were constituted, the vitamin C supplemented group and the control group, with the dietary vitamin C intake as the only statistical difference between groups. The duathlon competition induced a significant neutrophilia, which was higher in the supplemented group. Lymphocyte antioxidant enzyme activities increased after the competition, with a higher increase in SOD activity in the control group than in the supplemented one. The competition decreased neutrophil antioxidant enzyme activities and neutrophil ascorbate concentration. The decrease in the SOD activity in the supplemented group was higher than in the control group. Finally, the duathlon competition increased the expression of MAC-1 neutrophil adhesion molecule in the supplemented group. High vitamin C intake influenced the response of neutrophils and lymphocytes to oxidative stress induced by exercise, increasing the neutrophil activation.

[Immunomodulating action of fat-soluble vitamins after intense physical loading at low ambient temperatures]. / Immunomoduliruiushchee deistvie preparatov zhirorastvorimykh vitaminov posle intensivnykh fizicheskikh nagruzok, vypolniavshikhsia pri nizkoi temperature okruzhaiushchei sredy.

Introduced separately, preparations of the fat-soluble vitamins A, E and K decreased the expression of changes in the immunological reactivity and nonspecific resistance of Wistar rats after a 4-h swimming in water at a temperature of 10 +/- 2 degrees C. Joint administration of the vitamin preparations A + E or A + K normalized both the the immunological reactivity and nonspecific resistance of rats after cold swim test, while the joint introduction of vitamins E + K produces no such effect.

Effects of localized injections of neuropeptide Y antibody on motor activity and other behaviors.

Neuropeptide Y (NPY) was shown to increase feeding when injected into the hypothalamus. Neuropeptide Y antibody (aNPY) decreased feeding in the ventromedial area of the hypothalamus as well as when it was injected into the ventromedial or ventrolateral areas of the thalamus, but not when injected into other hypothalamic areas. The decrease in feeding produced by aNPY in the hypothalamus was associated with a sterotypic increase in general activity in the hypothalamus, circling in the ventromedial thalamic area, and barrel rolling in the ventrolateral thalamic area. Neuropeptide Y antibody also reduced by 54-73% the time it required for mice to recover from anesthesia. The marked increase in stereotypic activity and enhanced recovery from anesthetic suggest that blocking endogenous NPY released the brain areas from inhibitory control. These studies further confirm a physiological role for NPY in the central nervous system.