Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model.

Probiotics are referred to species of living microscopic organisms may help conserve the normal balance of the digestive system and/or manage diseases. A number of autoimmune, psychiatric, cardiovascular and cerebrovascular disorders may be associated with the imbalance of gut microbiota. This study examines the effect of 21 days consumption of multistrain probiotics on hippocampus injury, spatial and learning memory and some potential molecular mechanisms in a mouse model with cerebral hypoperfusion. Cerebral hypoperfusion was established in the mouse model by bilateral common carotid artery occlusion (BCCAO) for 20 min and 24 h reperfusion. Mixtures of several probiotic bacteria at concentrations of 107, 108 and 109 CFU/day were orally administrated for 3 weeks before the BCCAO. Spatial and learning memory, histological damage and apoptosis were assessed in the CA1, CA3 and dentate gyrus (DG) of the hippocampus 24 h after ischemia. The malondialdehyde (MDA) content and brain-derived neurotrophic factor (BDNF) level were measured by ELISA technique. Prophylactic of probiotic considerably reduced the number of apoptotic cells and neuronal death in the CA1, CA3 and DG of the hippocampus at all three concentrations (P < 0.001). In addition, probiotics reduced spatial memory impairment and neurological dysfunction only at the 109-CFU/day (P < 0.01). Nonetheless, probiotics did not change the levels of BDNF and MDA in the hippocampus (P > 0.05). According to the findings, the daily prophylactic ingestion of probiotics reduced hippocampus damage and prevented the spatial learning and memory deficit by suppressing apoptosis in the mouse model with cerebral hypoperfusion. Probiotic supplementation may be suggested as a useful preventive dietary strategy for groups susceptible to cerebrovascular diseases.

Effect of valerian on cognitive disorders and electroencephalography in hemodialysis patients: a randomized, cross over, double-blind clinical trial.

BACKGROUND: The prevalence of cognitive disorders in hemodialysis patients is twice as high as the general population, while these disorders often are undiagnosed. Timely prevention and treatment can improve their personal and social functions. Aim of study was determined the effect of Valerian on cognitive disorders and electroencephalography (EGG) in hemodialysis patients. METHODS: This crossover, double-blind clinical trial was conducted on 39 hemodialysis patients. The patients were randomly divided into two groups. Group A (n = 19) took Valerian capsules and Group B (n = 20) received placebo capsules 60 min before bedtime for one month. The type of treatment was replaced between the two groups after a one-month wash-out. The Mini Mental State Examination (MMSE) questionnaire was completed and EGG was performed before and after intervention in both periods. RESULTS: The cognitive scores of the Group valerian were increased significantly in the first (p = 0.003) and the second (p = 0.005) periods. In addition, the mean increase in the cognitive scores in the Group valerian was significant in the first (p = 0.028) and the second periods (p = 0.030). However, the changes in EGG showed no significant difference before and after intervention in two groups. CONCLUSION: The findings of this study indicated that valerian could be effective and significantly improve patients' cognitive status; however, no significant changes were observed in the electroencephalography of the hemodialysis patients. TRIAL REGISTRATION: IRCT201606076318N7 -2016-06-17.

Effects of extremely low frequency magnetic field on the development of tolerance to the analgesic effect of morphine in rats.

This study examined the effects of low frequency magnetic field (MF) on tolerance to analgesic effect of morphine in rats. Rats were made tolerant to morphine by injecting morphine (10 mg/kg, s) once daily for 8 consecutive days. Rats were simultaneously exposed to an MF (50 Hz at 1, 50, and 100 µT for 30 min) before, immediately, or 30 min after injection of morphine, and also exposed to a 0.5, 6, 12, and 30 Hz at 100 µT for 30 min before injection of morphine. The percentage of maximum possible effect of morphine (% MPE) was measured on the 1st, 4th, and 8th days by hot plate test. We observed that MF radiation (50 Hz at 1 µT and 30 Hz at 100 µT) immediately before and MF radiation (50 Hz at 100 µT) after morphine injection prevented the development of morphine tolerance compared to control. Also, we found that exposure to MF (50 Hz at 1, 50, and 100 µT) 30 min after injection of morphine failed to maintain the analgesic effect of morphine. Our results showed that exposure to low frequency electromagnetic field (30 and 50 Hz) immediately before or after the injection of morphine may be a potential method for treating the development of morphine tolerance in rats. Bioelectromagnetics. 38:618-625, 2017. © 2017 Wiley Periodicals, Inc.

Involvement of dopaminergic receptors of the rat nucleus accumbens in decreasing the conditioned place preference induced by lateral hypothalamus stimulation.

Our previous study showed that chemical stimulation of the lateral hypothalamus (LH) by carbachol can produce conditioned place preference (CPP) in rats. Also, it has been indicated that orexin activates the mesolimbic dopamine projecting neurons to the nucleus accumbens (NAc) and promotes the development of reward in rodents. Therefore, in this study, we tried to determine the role of intra-accumbal D1 and D2 dopamine receptors in the development (acquisition) of reward-related behaviors induced by chemical stimulation of the LH. Eighty-eight adult male Wistar rats were unilaterally implanted by two separate cannulae into the LH and NAc. For chemical stimulation of LH, carbachol (250nmol/0.5µl saline) was microinjected once daily during 3-days conditioning phase (acquisition period) of CPP paradigm. In the next experiments, different doses of D1 receptor antagonist, SCH23390 (0.25, 1 and 4µg/0.5µl saline) or sulpiride (0.25, 1 and 4µg/0.5µl DMSO) as a D2 receptor antagonist were unilaterally microinjected into the NAc, 5min prior to LH stimulation. One-way ANOVA showed that intra-accumbal administration of SCH23390 or sulpiride can decrease the development of LH stimulation-induced CPP in the rats. However, this decrease is more effective after blockade of the D2 dopamine receptor in the NAc. It seems that the dopaminergic system in this area is involved in place preference induced by LH stimulation.

Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats.

Although it is well established that chronic stress impairs spatial learning and memory, few studies have investigated possible ways to prevent its deleterious effects. Here, we investigated the effects of Crocus sativus L., commonly known as saffron, and its active constituent crocin on learning and memory loss and the induction of oxidative stress in the hippocampus by chronic stress. Rats were injected with saffron extract, crocin or vehicle over a period of 21 days while being exposed to chronic restraint stress (6 h/day). After this, they were trained and tested on a water-maze spatial memory task. They performed four trials per day for 5 consecutive days, and this was followed by a probe trial two days later. At the end of the behavioral testing, several parameters of oxidative stress in the hippocampus were measured. Treatment with saffron extract or crocin blocked the ability of chronic stress to impair spatial learning and memory retention. Relative to controls that received vehicle, stressed animals that received saffron extract or crocin had significantly higher levels of lipid peroxidation products, significantly higher activities of antioxidant enzymes including glutathione peroxidase, glutathione reductase and superoxide dismutase and significantly lower total antioxidant reactivity capacity. Finally, crocin significantly decreased plasma levels of corticosterone, as measured after the end of stress. These observations indicate that saffron and its active constituent crocin can prevent the impairment of learning and memory as well as the oxidative stress damage to the hippocampus induced by chronic stress. Thus, using these substances may be useful in pharmacological alleviation of cognitive deficits.

Evaluation of topical Matricaria chamomilla extract activity on linear incisional wound healing in albino rats.

In this investigation, the effect of Matricaria chamomilla extract on linear incisional wound healing was studied. Thirty male Wistar rats were subjected to a linear 3 cm incision made over the skin of the back. The animals were randomly divided into three experimental groups, as control, olive oil, and treatment. Control group did not receive any drug or cold cream. Olive oil group received topical olive oil once a day from beginning of experiments to complete wound closure. Treatment group were treated topically by M. chamomilla extract dissolved in olive oil at the same time. For computing the percentage of wound healing, the area of the wound measured at the beginning of experiments and the next 2, 5, 8, 11, 14, 17, and 20 days. The percentage of wound healing was calculated by Walker formula after measurement of the wound area. Results showed that there were statistically significant differences between treatment and olive oil animals (p < 0.05) in most of the days. We conclude that the extract of M. chamomilla administered topically has wound healing potential in linear incisional wound model in rats.

Antinociceptive effects of hydroalcoholic extract of Thymus vulgaris.

Previous investigation has shown that Thymus Vulgaris (TV) modulates pain. The aim of this work was to examine the role of TV on acute and chronic pain and compares its effect with dexamethasone (DEX) and stress (ST) by using hot plate, tail flick and formalin tests in mice. In this study male albino mice (25-30 g.) in 21 groups (n=147) were used. TV (100, 500 and 1000 mg/kg), DEX (0.5, 1 and 2 mg/kg) and vehicle (VEH) were injected 30 minutes before pain assessment tests. Stress was applied by 1 min swimming in cold water (18-22 degrees ). Acute and chronic pain was assessed by hot plate, tail flick and formalin tests. For assessment of the role of opioid receptors in antinoceception of TV extract, Naloxon (NAL, 2mg/kg, ip) as opioid receptor antagonist was injected before the injection of the more effective dose (500 mg/kg) of TV extract. Results indicated that TV, DEX and ST have analgesic effects in all tests (P<0.01 in comparison with control group). Above findings showed that TV extract, DEX and ST have modulatory effects on acute and chronic pain. Further research is required to determine the mechanisms by which TV extract has an inhibitory effect on pain sensation.

Antispasmodic effect of hydroalcoholic extract of Thymus vulgaris on the guinea-pig ileum.

The effects of Thymus vulgaris hydroalcoholic extract on the contractile responses of the isolated guinea-pig ileum were investigated. Contraction changes in the terminal ileum of guinea pigs were monitored using a force displacement transducer amplifier connected to a physiograph. Thymus vulgaris extract inhibited the contractile responses in a dose-dependent manner and also decreased the amplitude of peristaltic waves. It is concluded that T. vulgaris has an antispasmodic action on guinea pig ileum by decreasing the amplitudes of the muscle contractions during peristalsis. The EC50 was calculated as 1.7 mg mL(-1). In guinea-pig ileum the extract led to an antispasmodic effect, possibly by affecting the anticholinergic and serotoninergic pathways.

Antimotility effect of hydroalcoholic extract of yarrow (Achillea millefolium) on the guinea-pig ileum.

The use of medicinal herbs among the general population gives rise to the possibility of therapeutic or toxic effects in patients that use these plants. The effects of Achillea millefolium hydroalcoholic extract on the contractile responses of the isolated guinea-pig ileum were investigated. The effect of the Achillea millefolium extracts at five concentrations ranging form 0.05 to 5 mg mL(-1) was tested. The terminal ileum was removed. Segments were fixed in an organ bath containing in Tyrode solution. Contraction changes in the tissues were monitored using force displacement transducer amplifier connected to physiograph. Each segment served as its own control. Achillea millefolium inhibited the contractile response in a dose-dependent manner. The 50% effective concentration values (EC50) were calculated, which was 1.5 mg mL(-1). Regression analysis had shown that with increasing in extract concentration the effect of extract was increased. The coefficient of extract dose was 0.031 mg. Present results demonstrate that extract prepared from the plant of Achillea millefolium inhibited electrical induced contractions of the guinea-pig ileum when tested in vitro. This effect is dose dependent and reversible.