Autistic-like behaviors are attenuated by agmatine consumption during pregnancy: Assessment of oxidative stress profile and histopathological changes in the prefrontal cortex and CA1 region of the hippocampus.

Objectives: Due to the crucial role of polyamines during fetal growth and development, we aimed to determine the effect of prenatal administration of agmatine, an endogenous active metabolite of arginine, and a nutritional supplement, on autistic-like behaviors, oxidative-anti-oxidative profile, and histopathological changes of the prefrontal cortex (PFC) and CA1 area of the hippocampus in valproic acid (VPA) model of autism in male rats. Materials and Methods: VPA was injected intraperitoneally on embryonic days (ED) 12.5, and the pregnant rats were gavaged with agmatine between E6.5 to E18.5 (13 days), at doses of 0.001, 0.01, and 0.1 mg/kg. The autism-like behaviors and memory of male pups were analyzed via open-field, three-chamber, and novel object recognition tests. Serum oxidative stress and the histological changes in the PFC and CA1 were assessed at the end of the study. Results: The results suggest that prenatal agmatine reduced autistic-like behaviors by decreasing cell loss in CA1 and PFC. We observed no alterations in superoxide dismutase (SOD) level and total anti-oxidant capacity (TAC) between groups. VPA decreased catalase (CAT) activities, while agmatine decreased malondialdehyde (MDA) activity. Conclusion: Overall, this investigation suggests that agmatine may be a potential candidate for the early treatment and even prevention of appearance of autism symptoms.

Peroxisome proliferator-activated receptor-γ doesn't modify altered electrophysiological properties of the CA1 pyramidal neurons in a rat model of hepatic cirrhosis.

Regarding the low quality of life due to the cognitive complications in the patients with hepatic cirrhosis (HC), the goal of this study was to examine the possible neuroprotective effect of pioglitazone (PIO) on the electrophysiological alterations of hippocampus, a major area of cognition, in the experimental model of bile duct ligation (BDL). We used adult male Wistar rats in the present study to perform BDL or sham surgery. Pioglitazone was administered in BDL rats two weeks after the surgery for the next continuous four weeks. The effects of pioglitazone on BDL-induced electrophysiological alterations of the CA1 pyramidal neurons in the hippocampus were evaluated by whole-cell patch clamp recordings. Our findings demonstrated that chronic administration of PIO could not reverse the electrophysiological changes in the CA1 pyramidal neurons of the hippocampus in BDL rats but could improve the hepatic dysfunction.Together, the results of this study suggest that PIO administration cannot counteract altered intrinsic properties of the hippocampal neurons which has been shown recently as an involved mechanism of the cognitive impairments in hepatic encephalopathy (HE).

A Systematic Review of Death Anxiety and Related Factors Among Nurses.

This systematic review aimed to summarize the evidence regarding death anxiety (DA) and related factors among nurses. Scopus, PubMed, Web of Science, Iranmedex, and Scientific Information Database (SID) databases were extensively searched using purpose-related keywords from the earliest to October 5, 2021. A total of 6819 nurses were included in 31 studies. The DA of nurses based on the Templer's Death Anxiety Scale was moderate. Factors such as personal anxiety, frequency and severity of job stress, burnout, dying patient avoidance behavior, euthanasia, sex, mental health status, social desirability, attitude toward the elderly, humor, social maturity, psychological hardiness, quality of life, lack of social activity, self-efficacy, coping with death, and life satisfaction were associated with nurses' DA. Therefore, nursing policymakers can promote nurses' health to improve the quality of nursing care by considering these related factors.

Effect of Hydroalcoholic Extract of Stachys lavandulifolia on Pentylenetetrazole-induced Seizures in Male Mice: The Role of GABAergic and Opioidergic Systems.

Introduction: Epilepsy is one of the most common neurological disorders. Though there are several effective drugs for treating epilepsy, most drugs are associated with side effects and drug interactions. Stachys lavandulifolia used in Iranian traditional medicine has proven anti-anxiety and sedative properties. The current study aimed to evaluate the anticonvulsant effect of hydroalcoholic extract of S. lavandulifoliaon the Pentylenetetrazole (PTZ)-induced seizure in male mice and the role of benzodiazepine and opioid receptors. Methods: This study was conducted on 100 male mice, randomly categorized into 10 groups: Normal Saline (NS), two diazepam groups (0.025 and 0.1 mg/kg), three S. lavandulifolia extract groups (50, 100, and 200 mg/kg), diazepam 0.025 mg/kg+S. lavandulifolia extract 50 mg/kg, and three groups that pretreated with NS, flumazenil, or naloxone, 5 min before injection of 200 mg/kg S. lavandulifolia extract. After 30 min, PTZ (80 mg/kg) was injected into animals, and seizure indices were evaluated. Results: The S. lavandulifoliaextract attenuated the PTZ-induced seizures in a dose-dependent manner, and pretreatment with flumazenil reversed this effect. However, pretreatment with naloxone could not reverse this effect because seizure indices in the naloxone pretreated group were lower than that in the normal saline group. The combination of an ineffective dose of diazepam and S. lavandulifoliaextract decreased PTZ-induced seizures. Conclusion: The results of our study showed the anticonvulsant properties of hydroalcoholic extract of S. lavandulifolia. These effects might be due to the impact of the components of this extract on the central benzodiazepine system. Highlights: Hydroalcoholic extract of S. lavandulifolia attenuated the PTZ-induced seizures in a dose dependent manner.Pretreatment with flumazenil (blocker of benzodiazepines receptor) reversed anti-seizure effect of S. lavandulifolia extract.Combination of an ineffective dose of diazepam and S. lavandulifolia extract decreased PTZ-induced seizures. Plain Language Summary: Epilepsy is one of the most common neurological disorders after stroke and is characterized by recurrent seizures due to abnormal excessive neural activity in the brain. Although there are many anticonvulsant drugs on the market, not all patients with epilepsy can be treated and one-third of patients suffer from recurring epilepsy despite using different antiepileptic drugs and more than 50% of them show side effects drugs during treatment. So, it is necessary to conduct further studies to develop more effective anti-epilepsy drugs with the minimum side effects. In recent years, plenty of studies have been conducted on medical plants, and S. lavandulifolia reported among the Iranian traditional medicine with antianxiety and sedative features. Some studies have mentioned the sedative and anti-inflammatory function of S. lavandulifolia, and its significant effects on anxiety have been approved comparable to diazepam. Overall, considering the anti-anxiety, analgesic, and sedative effects of the hydroalcoholic extract of S. lavandulifolia, it might possess anti-convulsive effects, too. The purpose of the current study was designed to investigate whether the effect of intra peritoneal injection of hydroalcoholic extract of S. lavandulifolia on the PTZ-induced convulsion in male mice and assessed the role of benzodiazepine and opioid receptors. Results of this study demonstrated that S. lavandulifolia extract attenuated the PTZ-induced seizures in a dose dependent manner, and pretreatment with flumazenil (blocker of benzodiazepines receptor) reversed this effect. However, pretreatment with naloxone (Non-selective blocker of opioids receptor) could not reverse this effect but the combination of an ineffective dose of diazepam and S. lavandulifolia extract decreased PTZ-induced seizures, thus anti-epileptic effect of S. lavandulifolia mediated by benzodiazepine receptors.

Successful restoration of knee extension after transferring of the anterior branch of the obturator nerve: a case study.

Objective: Femoral nerve palsy occurs after trauma, surgical procedures and tumors and leads to loss of quadriceps functions, disability and decreased quality of life. The aim of this report was to describe a successful restoration of knee extension by transferring the anterior branch of the obturator nerve to selective branches of the femoral nerve at the thigh level.Methods: We describe a 27-year-old male who had quadriceps femoris muscle paralysis after surgical evacuation for retroperitoneal hematoma five months ago. Since proximal stump of femoral nerve was not accessible, we transferred anterior branch of obturator nerve to selective branches of femoral nerve for reconstruction of quadriceps femoris muscle.Results: After four months, he regained quadriceps muscle strength M3 and began to walk. He achieved full muscle strength (M5) nine months after surgery and was able to walk up-stairs easily 14 months after surgery and atrophy of the quadriceps was improved.Conclusion: The anterior branch of the obturator nerve is an available donor nerve with an excellent functional recovery for the reconstruction of knee extension when proximal stump of femoral nerve is not reachable or the repair needs a long graft.

Vitamin D status and disability among patients with multiple sclerosis: a systematic review and meta-analysis.

Association between the serum vitamin D level and disability of patients with multiple sclerosis (MS) has been investigated during several researches. However, these studies reported different results. The current study aims to estimate the correlation between the concentrations of 25 (OH) vitamin D and the level of disability among MS patients. Using Mesh and non-Mesh terms related to MS, disability level and vitamin D, different data banks were searched. Required information was extracted from the selected eligible primary articles. Stata version 11 software was applied for combining the primary correlation coefficients using random effect model. The effect of MS type and patients' age was assessed using meta-regression models. Sensitivity analysis was performed to investigate the role of each primary study in the pooled estimate. Egger test was applied to find any publication bias. Of 14 eligible studies, the total correlation coefficient (95% confidence interval) between 25 (OH) vitamin D level and disability in both sexes as well as among female was estimated as of -0.29 (-0.40, -0.17) and -0.35 (-0.46, -0.24) respectively. Two articles carried out among male did not report significant results. Our meta-analysis showed a significant negative correlation between 25 (OH) vitamin D level and disability of MS patients so that the disability reduces with increasing the 25 (OH) vitamin D level.

Ischemic Postconditioning Attenuates Bilateral Renal Ischemia-induced Cognitive Impairments.

Introduction: Acute Kidney Injury (AKI) is a frequent complication of kidney failure with high mortality, leading to brain dysfunction. This study aimed to investigate the possible protective effect of Ischemic Postconditioning (IPo) against brain dysfunction induced by Bilateral Renal Ischemia (BRI). Methods: Male Wistar rats underwent BRI, sham, or IPo surgery 24h and 1w after reperfusion. The rats' explorative behaviors and motor function were evaluated by an open field, rotarod, and wire grip tests. The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Western blotting was performed to evaluate hippocampal Brain-Derived Neurotrophic Factor (BDNF) expression. Results: The impairment of balance function induced by BRI was not reversed; however, passive avoidance learning impairment was reversed by postconditioning 24h after reperfusion. IPo increased muscle strength compared to the BRI group; however, explorative behaviors and balance function had no difference 1w after reperfusion. BRI significantly decreased the BDNF protein expression in the hippocampus, and postconditioning increased 24h after reperfusion. Conclusion: The obtained results demonstrated the deleterious effect of BRI on cognitive and balance function 24h after reperfusion. IPo indicated a curative effect against cognitive dysfunction probably by enhancing BDNF protein expression in the hippocampus. Highlights: IPo improved passive avoidance learning impairment induced by BRI.IPo increased muscle strength compared to the BRI group.BRI significantly decreased the BDNF protein expression in the hippocampus.IPo increased BDNF protein expression 24h after reperfusion. Plain Language Summary: Acute kidney injury may be associated with numerous complications in different regions of brain, as it may alter the permeability of the blood-brain barrier, accumulate the toxins, decreased blood flow to the brain, increased risk of encephalopathy, higher mental dysfunctions like delirium, stroke, memory and thinking problems (dementia) in people with kidney failure. It has been demonstrated that the most common causes of mortality in acute kidney injury is brain dysfunction. Therefore, discovering new treatments can decrease the brain injuries and help the patients with kidney dysfunction to have a higher quality of life. Ischemic postconditioning, which refers to a series of brief ischemia and reperfusion cycles applied immediately at the site of the ischemic organ after reperfusion, results in reduced injuries induced by ischemia. The purpose of the current study was designed to investigate whether ischemic postconditioning exerts neuroprotective effects against brain dysfunctions induced by renal ischemia in rats. Results of this study demonstrated that acute kidney injury triggers distant organ dysfunction and leads to cognitive and balance dysfunction 24h after induction of renal ischemia and ischemic postconditioning protects the brain as a remote organ against cognitive dysfunction from the injury induced by renal ischemia.

Interaction of morphine tolerance with pentylenetetrazole-induced seizure threshold in mice: The role of NMDA-receptor/NO pathway.

N-methyl-d-aspartate receptor (NMDA-R)/nitric oxide (NO) pathway is involved in the intensification of the analgesic effect of opioids and the reduction of the intensity of opioids tolerance and dependence. In the current study, we investigated the involvement of NMDA-R/NO pathway in chronic morphine-treated mice in both the development of tolerance to the analgesic effect of morphine and in pentylenetetrazole (PTZ)-induced seizure threshold. Chronic treatment with morphine (30 mg/kg) exhibited increased seizure resistance in morphine-induced tolerant mice. The development of morphine tolerance was withdrawn when used concomitantly with NOS inhibitors and NMDA-R antagonist, suggesting that the development of tolerance to the anticonvulsant effect of morphine (30 mg/kg) is mediated through the NMDA-R/NO pathway. A dose-dependent biphasic seizure modulation of morphine was demonstrated in the acute treatment with morphine; acute treatment at a dose of 0.5 mg/kg shows the anticonvulsant effect and at a dose of 30 mg/kg shows proconvulsant effect. However, a different pattern was observed in the mice treated chronically with morphine: they demonstrated tolerance in the tail-flick test; five consecutive days of chronic treatment with a high dose of morphine (30 mg/kg) showed anticonvulsant effect while a low dose of morphine (0.5 mg/kg) showed a proconvulsant effect. The anticonvulsant effect of morphine was inhibited completely by the concomitant administration of NO synthase (NOS) inhibitors including nonspecific NOS inhibitor (L-NAME, 10 mg/kg), inducible NOS inhibitor (aminoguanidine, 50 mg/kg), and neuronal NOS inhibitor (7-nitroindazole (7-NI), 15 mg/kg) for five consecutive days. Besides, five days injection of NMDA-R antagonist (MK-801, 0.05 mg/kg) significantly inhibited the anticonvulsant effect of morphine on the PTZ-induced clonic seizures. The results revealed that chronic treatment with morphine leads to the development of tolerance in mice, which in turn may cause an anticonvulsant effect in a high dose of morphine via the NMDA-R/NO pathway.

Soleus nerve transfer to deep peroneal nerve for treatment of foot drop.

Different mechanisms including knee dislocation, replacement surgery, nerve tumor, lumbar disc herniation, sharp injury, and gunshot wound lead to foot drop. Several surgical techniques have been used for treatment of foot drop, however, they have had sub-optimal outcomes. Soleus branch of tibial nerve is a good donor for nerve transfer for treatment of foot drop. In this is retrospective study, we reviewed medical records of 6 consecutive patients with sustained foot drop following injury to lumbar root or peroneal nerve, who underwent transfer of the soleus branch of tibial nerve to deep peroneal nerve during 2014-2016. The mean age of the patients was 44.8 years and duration of injury to surgery and follow-up was 8.3 and 14.6 months, respectively. At the end of the follow-up, ankle dorsiflexion force was M4 in two patients (with traumatic peroneal nerve injury with M3 toe extension) and was M2 in one patient. There were three patients with lumbar degenerative disease. Of these patients, two showed M0 and one patient experienced M1 ankle dorsiflexion. We recommend that transfer of soleus nerve to deep peroneal nerve is used as an alternative technique for treatment of foot drop.

Effects of Hemodynamic Factors and Oxygenation on the Incidence of Pressure Ulcers in the ICU.

OBJECTIVE: To investigate the roles of hemodynamic factors and oxygenation on the incidence of pressure ulcers in patients in the ICU on mechanical ventilation. METHODS: This prospective analytical cross-sectional study was performed in several ICUs for a period of 8 months in Iran. Researchers checked patients for pressure ulcers on a daily basis. They collected demographic, hemodynamic, and oxygenation data until a pressure ulcer occurred, the patient's artificial airway was removed, the patient died, or the patient was discharged. RESULTS: From August 2017 to February 2018, a total of 2,581 patients were admitted to the study ICUs; of these, 133 patients were eligible for the study. The results indicated that 41.4% (n = 55) of the patients ended up with pressure ulcers. Investigation of the variables using a Cox regression model showed that, among other variables considered in this study, age, mean arterial pressure, and positive end-expiratory pressure in the mechanical ventilator can contribute to the risk of pressure ulcers. CONCLUSIONS: Providers should pay attention to changes in hemodynamic parameters, especially mean arterial pressure; carefully determine the most appropriate positive end-expiratory pressure for patients connected to mechanical ventilation; and take special care of susceptible groups such as older adults and hospitalized patients to decrease the incidence of pressure ulcers.

Methadone's effects on pentylenetetrazole-induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling.

Methadone is a synthetic opioid used to treat opiate withdrawal and addiction. Studies have demonstrated the impact of methadone on seizure susceptibility. This study investigated the modulatory impacts of acute and subchronic (three times daily for 5 days) intraperitoneal methadone treatment on pentylenetetrazole-induced clonic seizure threshold (CST) in mice, as well as the involvement of the nitric oxide, N-methyl-d-aspartate (NMDA), and µ-opioid pathways. Acute administration of different doses of methadone (0.1, 0.3, 1, and 3 mg/kg) 45 min before CST significantly decreased the seizure threshold. Additionally, pretreatment with noneffective doses of an opioid receptor antagonist (naltrexone) and NMDA receptor antagonists (ketamine and MK-801) inhibited methadone's proconvulsive activity in the acute phase, while l-NAME (a nonspecific nitric oxide synthase (NOS) inhibitor) did not affect that activity. In the subchronic phase, methadone (3 mg/kg) demonstrated an anticonvulsive effect. Although subchronic pretreatment with noneffective doses of l-NAME and 7-nitroindazole (a specific neuronal NOS inhibitor) reversed methadone's anticonvulsive activity, aminoguanidine (a specific inducible NOS inhibitor), naltrexone, MK-801, and ketamine did not change methadone's anticonvulsive characteristic. Our results suggest that NMDA and µ-opioid receptors may be involved in methadone's proconvulsive activity in the acute phase, while methadone's anticonvulsive activity may be modulated by neuronal NOS in the subchronic phase.

Peroxisome proliferator-activated receptor-γ activation attenuates harmaline-induced cognitive impairments in rats.

Cognitive and motor disturbances are serious concerns of the tremors induced by motor disorders. Despite the lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. Recent studies have shown that PPAR-γ agonists have neuroprotective effects. In the current study, the effects of pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma agonist, on harmaline-induced motor and cognitive impairment were studied. Male Wistar rats were divided into vehicle (normal saline), PIO (20 mg/kg i.p.), harmaline (10 mg/kg, i.p.) and PIO + harmaline (PIO injected 2 h before harmaline) groups. Open field, rotarod, wire grip, foot print and Morris water maze tests were used to evaluate the motor and cognitive performance. The results indicated that administration of PIO attenuated harmaline-induced locomotor, anxiety-like behaviors, and spatial learning and memory impairments, but it partially decreased the tremor score. The neuroprotective and anxiolytic effects of PIO demonstrated in the current study can offer the PPAR-γ receptor agonism as a potential therapeutic agent in the treatment of patients with tremor that manifest mental dysfunction.

Effects of erythropoietin on bile duct ligation-induced neuro-inflammation in male rats.

Hepatic encephalopathy (HE) is a brain disorder as a result of liver failure. Previous studies have indicated that erythropoietin (EPO) has neuroprotective effects in different neurological diseases. This study addressed the therapeutic effect of a four-week treatment with EPO on neuronal damages in bile duct-ligated rats. Forty male Wistar rats (250-280 g) were used in the present study. The animals were randomly divided into four groups consisting of 10 animals each, including sham, sham + EPO, bile duct ligation (BDL), and BDL + EPO. EPO was intraperitoneally administered every other day (5,000 U/Kg) in the last four weeks after BDL. Biochemical and histological studies were performed to evaluate neurodegeneration. The results revealed that BDL increases the level of hepatic enzymes and total bilirubin. Furthermore, neurodegeneration was significantly increased in the BDL group compared to sham groups. EPO preserved hepatic enzymes and total bilirubin in the treated group. In addition, EPO significantly decreased the neurodegeneration in BDL + EPO compared to the BDL group. Results of this study showed that EPO has neuroprotective effects in the rat model of HE, possibly due to its anti-inflammatory and anti-oxidant properties. Complementary studies are required to clarify the exact mechanisms.

Angiotensin II type 1 receptor blocker losartan attenuates locomotor, anxiety-like behavior, and passive avoidance learning deficits in a sub-chronic stress model.

OBJECTIVES: Stress alters sensory and cognitive function in humans and animals. Angiotensin (AT) receptors have demonstrated well-established interactions in sets of physiological phenomena. AT1 receptors can play a part in stress-induced activation of hypothalamic-pituitary-adrenal (HPA) axis; besides angiotensinergic neurotransmission plays a pivotal role in stress-evoked physiological responses. AT1 receptors are also involved in nociception and memory. The objective of the current study was to evaluate the effects of losartan as an AT1R antagonist in locomotor activity, nociception and memory impairments induced by sub-chronic swim stress. MATERIALS AND METHODS: A two-session forced swimming stress protocol was administered to the rats. Pretreatment with losartan (10 mg/kg, IP) or saline was made before each swimming session. Locomotor activity, anxiety-like behavior, nociception, and passive avoidance learning were evaluated 24 hr after last swim stress session. RESULTS: Swim stress induced increased anxiety-like behavior in the open field test, which pretreatment with losartan did counterbalance. Increased thermal threshold was observed in the nociceptive measurement after swim stress. Pretreatment with losartan attenuated the increased threshold and also inhibited a decreased step-through latency that was observed in the memory paradigm after swim stress. CONCLUSION: The results of this study indicate that sub-chronic swim stress impairs passive avoidance learning, anxiety-like behaviors, and nociception; and AT1 receptor seems to have a modulatory role in these alterations. However, further studies are suggested to examine the protective effect of AT1R inhibitors on stress-induced impairments in sensory and cognitive function.

Effects of Modafinil on Clonic Seizure Threshold Induced by Pentylenetetrazole in Mice: Involvement of Glutamate, Nitric oxide, GABA, and Serotonin Pathways.

Epilepsy is the third most common chronic brain disorder. Modafinil is an awakening agent approved for narcolepsy. In addition to its clinical uses some reports revealed that modafinil was associated with some alterations in seizure threshold. The purpose of this study was to clarify the effect of acute administration of modafinil in clonic seizure threshold (CST) induced by pentylenetetrazole in mice and the involvement of glutamate, nitric oxide, gamma amino butyric acid (GABA), and serotonin systems in this feature. Modafinil at 80 and 150 mg/kg showed anti- and pro-convulsant effects respectively and expressed maximum anti- and pro-convulsant activities at 30 min after injection. Both modulatory effects were blunted by pretreatment of L-NAME [nonspecific nitric oxide synthase (NOS) inhibitor; 10 mg/kg, i.p.], 7-nitroindazole (a neuronal NOS inhibitor; 40 mg/kg, i.p.), and aminoguanidine (an inducible NOS inhibitor; 50 mg/kg, i.p.). Injection of the NOS precursor L-arginine (60 mg/kg, i.p.) before modafinil did not change the anti-convulsant effect, while thoroughly reversed the pro-convulsant one. Our experiments displayed that administration of diazepam (a GABAA receptor agonist; 0.02 mg/kg, i.p.) and MK-801 (a NMDA receptor antagonist; 0.05 mg/kg, i.p.) before different doses of modafinil significantly increased CST. Finally, pretreatment of citalopram (a selective serotonin reuptake inhibitor; 0.1 mg/kg, i.p.) did not modify the convulsant activities of modafinil. Therefore, nitric oxide system may mediate anti-convulsant activity, while glutamate, nitric oxide, and GABA pathways may involve in pro-convulsant property. Serotonin receptors have no role on convulsant effects of modafinil.

Pre-Treatment with Erythropoietin Attenuates Bilateral Renal Ischemia-Induced Cognitive Impairments.

One of the most common causes of mortality in acute kidney injury is brain dysfunction. Here we investigated the possible protective effect of erythropoietin (EPO) on cognitive impairments induced by bilateral renal ischemia (BRI). Eighty male Wistar rats were allocated into 8 groups: 1, 2) Sham +V (Vehicle), 3, 4) Sham+EPO, 5, 6) BRI+V, 7, 8) BRI+EPO. The groups followed by the reperfusion periods of 24hours (24 h) and 1week (1w). EPO or saline was administrated 30 min before surgery (1000 IU/kg, i.p). The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Hippocampal brain-derived neurotrophic factor (BDNF) protein expression was assessed by western blotting. BUN (blood urea nitrogen) and creatinine (Cr) concentrations were significantly increased in BRI+V group 24 h after reperfusion. BRI+V rats had just an increased level of BUN but not Cr 1w after reperfusion. EPO reversed passive avoidance learning impairments observed in BRI+V group 24 h after reperfusion. There were no significant differences in spatial and passive avoidance learning between experimental groups 1w after reperfusion and histological evaluation confirmed the behavioral data. BRI significantly decreased the BDNF protein expression in the hippocampus and EPO increased that 24 h after operation. These observations showed protective effect of EPO against cognitive dysfunctions following BRI 24 h after reperfusion through increase in BDNF protein expression.

Psychological stress has a higher rate of developing addictive behaviors compared to physical stress in rat offspring.

Prenatal stress could have great influence on development of offspring and might alter cognitive function and other physiological processes of children. The current study was conducted to study the effect of physical or psychological prenatal stress on addictive and anxiety-like behavior of male and female offspring during their adolescence period (postnatal day (PND) 40). Adult female rats were exposed to physical (swimming) or psychological (observing another female rat swimming) stress from day six of gestation for 10 days. Male and female offspring were assayed for anxiety-like behavior, motor and balance function and morphine conditioned place preference using the open field, elevated plus maze (EPM), rotarod and wire grip assay and conditioned place preference. Offspring in both physical and psychological prenatal stress groups demonstrated significant increase in anxiety-like behavior in EPM paradigm, but no alterations were observed in motor and balance function of animals. Offspring in the psychological prenatal stress group had an increased preference for morphine in comparison to control and physical prenatal stress groups. Results of the current study demonstrated that animals exposed to psychological stress during fetal development are at a higher risk of developing addictive behaviors. Further research might elucidate the exact mechanisms involved to provide better preventive and therapeutic interventions.

Nitric oxide pathway presumably does not contribute to antianxiety and memory retrieval effects of losartan.

Nitric oxide (NO) and angiotensin (AT) receptors have demonstrated well-established interactions in various physiological phenomena. AT1 receptors can play a part in stress-induced activation of the hypothalamic-pituitary-adrenal axis; also, angiotensinergic neurotransmission plays a pivotal role in stress-evoked physiological responses. On the basis of the stress-modulating characteristics of NO, AT1, and AT2 receptors, the present study evaluated the roles of NO and AT1 receptors in the attenuation of stress-induced anxiety-like behaviors after administration of losartan, an AT1 antagonist. Male Wistar rats were exposed to the communication stress box, using a novel method to induce physical or emotional stress, and losartan (10 mg/kg), losartan+L-NG-nitroargininemethyl ester (L-NAME), L-NAME (1, 10, and 100 mg/kg), and normal saline-treated groups were compared. Losartan had reduced behavioral changes induced by both types of stressor and enhanced memory retrieval. Anxiety-like behaviors were significantly attenuated by administration of losartan, to a greater extent in the emotional rather than physical stress group. None of the injected dosages of L-NAME reversed the antianxiety and memory retrieval effects of losartan. Our results indicate that losartan probably improves memory retrieval and lessens anxiety-like behaviors through mechanisms other than the NO pathway.

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties.

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.

Evaluation of prepulse inhibition and memory impairments at early stage of cirrhosis may be considered as a diagnostic index for minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE), which represents the early stage of this condition, is not clinically apparent and is prevalent in up to 80% of patients. The poor outcomes of MHE encouraged us to identify more simple methods for early diagnosis of MHE. To this purpose, we evaluated the contemporary manifestations of motor, cognitive and sensorimotor gaiting deficits following bile duct-ligation (BDL). Male Wistar rats were undergone BDL to induce cirrhosis and locomotor, spatial learning and memory and sensorimotor gating were assessed 2, 3, and 4weeks after the operation by rotarod, Morris water-maze and prepulse inhibition (PPI) tests. PPI was examined 6weeks after BDL until appearance of hepatic encephalopathy. Results showed that although PPI was significantly enhanced in the 6-week BDL animals, locomotor activity reduced in 4-week BDL rats compared to the BDL rats after a 2-week period. The total distance travelled and swimming time to reach the platform increased in the 4-week BDL rats and, in contrast, the percentage of time spent and space travelled in correct quadrant decreased. Moreover, memory index decreased in the 3-week BDL group compared to sham-operated group. It was observed an increase in global PPI in 3- and 4-week BDL animals in comparison with either 2-week BDL or sham-operated rats. Consequently, it is indicated that BDL animals manifest spatial learning and memory deficits and PPI disruption in early stage of HE and evaluation of these factors can be considered as indices for simple and early diagnosis of MHE.