Modafinil Improves Autism-like Behavior in Rats by Reducing Neuroinflammation.

To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male Wistar rats were used in the study, divided into 3 groups of ten subjects. One group served as a control, the subjects in the other two were given 250 mg/kg/day of PPA by intraperitoneal injection over the course of 5 days to induce autism. The experimental design was as follows: Group 1: Normal control (orally-fed control, n = 10); Group 2 (PPA + saline, n = 10): PPA and 1 ml/kg/day % 0.9 NaCl saline via oral gavage; Group 3 (PPA + Modafinil, n = 10) PPA and 30 mg/kg/day Modafinil (Modiodal tablets 100 mg, Cephalon) via oral gavage. All of the groups were investigated for behavioral, biochemical, and histological abnormality. Autism-like behaviors were reduced significantly in the rats treated with PPA. TNF-α, Nerve Growth Factor (NGF), IL-17, IL-2, and NF-KB levels as well as MDA levels and lactate were significantly higher in those treated with PPA compared to the control group. Using immunohistochemical methods, the number of neurons and GFAP immunoreactivity was significantly altered in PPA-treated rats compared to the control. Using Magnetic Resonance Spectroscopy (MRS), we found that lactate levels were significantly higher in the PPA-treated rats, while creatinine levels were significantly decreased. In the rats administered with Modafinil, behavior, neuroinflammation, and histopathological changes brought about by PPA were significantly reversed. Our results demonstrate the potential role of Modafinil in ameliorating PPA-induced neuroinflammation in rats.

Clinical-epidemiological and radiological characteristics of stroke patients: A multicentre study.

INTRODUCTION AND AIM: Stroke is the leading cause of disability in adults and the second most common cause of death, at a rate of 11.8% worldwide. The purpose of this study was to examine the aetiological, demographic, and clinical characteristics of patients admitted to hospital because of acute strokes. MATERIALS AND METHODS: This multicentre study retrieved information for all patients admitted to hospital because of an acute cerebrovascular event over a six-month period, and sociodemographic, aetiological, and clinical characteristics were recorded. RESULTS: A total of 1136 patients, 520 of whom were women (45.7%), with a mean age of 70.3 ± 12.8 years, were included in the study. Of these, 967 were diagnosed with ischaemic stroke (IS) (85.1%), 99 with haemorrhagic stroke (HS) (8.7%), and 70 with transient ischaemic attack (6.1%). The most common risk factor for stroke was hypertension (73%). Carotid disease and hyperlipidaemia rates were higher in patients with HS. Numbers of functionally dependent patients with severe neurological status according to the National Institutes of Health Stroke Scale and modified Rankin scale were significantly higher in the HS group (P < .001). When IS was classified according to the Trial of Org 10172 in Acute Stroke Treatment, small vessel disease emerged as the most common cause (41%). The most common lesion localisations were the parietal lobe (23%) in the IS group and the thalamus (35.3%) in the HS group. Eighty-eight patients (7.7%), 62 (6.4%) in the ischaemic subgroup, and 26 (26.3%) in the haemorrhagic subgroup, died within the first month. CONCLUSION: Current and accurate evaluations of stroke aetiology are essential for stroke prevention and treatment planning. This study, shows that no change occurred in the aetiology of stroke and epidemiological characteristics and that accurate identification of modifiable stroke risk factors is still a major goal.

Exposure to hypertonic solutions during pregnancy induces autism-like behaviors via the NFAT-5 pathway in offspring in a rat model.

OBJECTIVES: to investigate the effects of hyperosmolar state (HS) on immune response and inflammation via the NFAT5 pathway and examine whether immune-mediated conditions trigger autism-like behavior in offspring. METHODS: a pregnant rat model was performed by administering hyperosmotic solutions. Pregnant rats were divided into 2 main groups; control (group I) and hyperosmolar groups (group II). Control group rats were given % 0.25 NaCI (tap water) (n = 6), the Hyperosmolar (HO) group was further subdivided into 3 groups as; Group II a rats which were given % 3 hypertonic NaCl (n = 6), Group II b rats were given mineral water (% 3 NaHCO3+magnesium+calcium content) (n = 6), and Group II c rats were given Ayran (% 0.8 NaCl content) (n = 6). Their offspring were examined for behaviors, biochemical and histological abnormality. RESULTS: in offspring, TNF- α, IL-17, NFAT-5, and NGF levels in the brain were significantly higher in hyperosmotic solution groups than in control rats. Exposure of pregnant rats to hyperosmotic solution resulted in autism-like behaviors in their offspring. Through immunohistochemical methods, we found that CA1 and CA2 of the hippocampus indicated decreased number of neurons in hyperosmotic solution groups compared with the control group. CONCLUSIONS: our findings once again emphasized that the immune-mediated conditions involved in the pathophysiology of autism. NFAT5 pathway may be a key factor in the development of neuroinflammation by hyperosmotic solutions.

Repeated gadoteric acid and gadobutrol exposure causes deterioration of behavior and memory functions in rats: MRI, histopathological and biochemical evidence.

Gadolinium-based contrast agents (GBCAs) exert effects in different regions of the brain; however, studies on this topic are mostly focused on radiological outcomes of GBCA exposure. This paper is a preliminary attempt to identify whether there are changes in behavioral, cognitive, histopathological, radiological and biochemical characteristics with repeated exposure to gadobutrol and gadoteric acid. The effects of GBCAs were tested with the assessment of 4 groups -each comprised of 6 rats [controls, gadobutrol, gadoteric acid (Doteram), and gadoteric acid (Clariscan)]. Respective treatments of 0.1 ml/kg were administered for 3 weeks, followed by a recovery period of 1 week without any treatment. At the end of this regimen, behavioral tests (open field and passive learning test) were performed. Additionally, histopathological analysis of the hippocampal CA1 and CA3 regions (GFAP measurement and total neuron count), biochemical measurements [TNF-a, Malondialdehyde (MDA), Superoxide dismutase (SOD), homovalinic acid (HVA) and choline acetyl transferase (ChAT) levels], and radiological findings (MRI-region of interest) were carried out in each group. There was a significant impairment in all groups that had received gadolinium in open field and passive avoidance learning tests. Oxidative stress and inflammation markers were significantly elevated in all gadolinium groups. Additionally, increased hippocampal gliosis and decreased MRI-ROIs were observed in rats exposed to gadolinium. Chronic gadoteric acid and gadobutrol exposure causes hippocampal gliosis and elevates oxidative stress and inflammation in rats. Radiological outcomes are also consistent with these findings. Long-term studies might be required to conclude whether gadolinium deposition in the brain causes subtle neurological deficits.

Assessment of the relation between the neutrophil to lymphocyte ratio and severity of ischemic stroke in a large cohort.

AIM OF STUDY: The NLR is a simple and inexpensive parameter that is useful as a marker of subclinical inflammation. The purpose of this study was to investigate the clinical characteristics of patients diagnosed with acute cerebral ischemia at the time of initial evaluation in the emergency department. PATIENTS AND METHODS: The study was designed as a multicentre cross-sectional study of acute ischemic stroke patients. Neurological evaluations were assessed using the NIHSS and mRS. Evaluations included the results of patients' laboratory tests performed at the time of presentation to the emergency department. RESULTS: Seven hundred and thirty-five ischemic stroke patients were included in the study. Stroke cases assessed by the mRS as mild or severe showed significant differences with respect to age, leukocyte counts, neutrophil counts, NLR, LDL cholesterol values, and serum glucose values (P = .001). When analysed using NIHSS, lymphocyte levels were significantly higher in very severe stroke cases compared with mild, moderate, and severe cases. NLR was also significantly higher in very severe stroke cases and severe stroke cases as compared with the mild and moderate stroke groups. Neurological evaluations assessed using the mRS showed a mild positive correlation with neutrophil and leukocyte count and a weak correlation with the NLR. CONCLUSION: The NLR exhibited a significant correlation with the results of the mRS and NIHSS. The NLR measured in the very early period was also significantly associated with clinical condition. These results suggest that high NLR values may be a marker of stroke' severity.What's known Stroke is an important disease that has a significant impact on mortality and morbidity and is closely related to the aging world population. In recent years, highly innovative approaches have been developed in the treatment of stroke. Although a long distance has been covered in the early diagnosis of stroke, the ability to predict the severity of the disease with many parameters is still up to date. What's new At the time of admission, in the absence of infection, parameters such as leukocytelymphocyte count and NLR may be telling about stroke severity. Demonstrating the utility of these simple, practical, inexpensive and naninvasive parameters to predict stroke severity can contribute to the scoring to be established at the time of initial diagnosis.

The prevalence of restless legs syndrome in patients undergoing coronary angiography and its relationship with the severity of coronary artery stenosis.

PURPOSE: Results from studies on the relationship between restless legs syndrome (RLS) and coronary artery disease (CAD) are conflicting. Some studies associate RLS with CAD by heart rate variability, blood pressure variability, and other autonomic, neuronal reasons, while other studies do not support these observations. The aim of this study was to investigate the prevalence of RLS in patients undergoing coronary angiography for CAD and to assess RLS prevalence with severity of CAD. METHODS: After inclusion and exclusion criteria were applied, enrolled patients with less than 50% coronary artery stenosis by angiography (0-49%) were assigned to group 1, and patients with 50% or more coronary artery stenosis were assigned to group 2. Patients were diagnosed with RLS if they met all five essential criteria of the International RLS study group. RLS prevalence and other comorbidities were compared between the two groups. RESULTS: Of 126 patients, 74 men (59%), mean age 64.0 ± 8.7 years, mean BMI 29.6 kg/m2, 47 (37%) were assigned to group 1 (no or nonobstructive CAD) and 79 (63%) were assigned to group 2 (obstructive CAD). No significant differences were found between the groups in terms of mean age, BMI, gender, or prevalence of hypertension, hypercholesterolemia, and DM. The prevalence of RLS in group 2 (29%) was significantly higher than in group 1 (15%), p = 0.013. CONCLUSION: These results suggest that prevalence of RLS is associated with CAD and with CAD severity. We conjecture that RLS may be related to vascular endothelial dysfunction in cardiovascular disease.

Chronic Oxytocin treatment has long lasting therapeutic potential in a rat model of neonatal hypercapnic-hypoxia injury, through enhanced GABAergic signaling and by reducing hippocampal gliosis with its anti-inflammatory feature.

Previous studies have shown that, oxytocin has anticonvulsant and neuroprotective effects. One of the most important complications of Hypercapnic-hypoxia is drug resistance epilepsy. Effects of chronic intraperitoneal oxytocin treatment on gliosis, neuroinflammation and seizure activity was investigated in a model in which rats were exposed to hypoxia on postnatal day 1 and later challenged to the seizure-inducing pentylenetetrazol Forty pups were included in the study on their first day of birth. 16 pups were exposed to 100% CO2 for 5 minutes and other 16 pups for 10 minutes. The remaining 8 pups comprised the control group. Groups were classified according to oxytocin administration within the first 4 weeks. Pentylenetetrazol was administered 6 months after the oxytocin treatment. The Racine's Convulsion Scale and onset times of first myoclonic jerk (FMJ) were evaluated. To determine the mechanisms by which oxytocin exerted its effects on hypercapnic-anoxia exposed rats, we performed CA1 total neuron count & CA1 GFAP immunostaining, and measured brain levels of TNF-α and GAD-67. The Racine scale and TNF-α values were significantly lower in both groups that received oxytocin, while time-to-FMJ and GAD-67 level were significantly higher. The histopathological evaluations showed that oxytocin had significant ameliorative effects (especially regarding gliosis) on the hippocampus of hypoxic rats. Regarding the results of present study, it can be speculated that after acute hypercapnic-anoxia exposure, chronic Oxytocin treatment has long lasting therapeutic potential on rats, possibly by reducing the gliosis with its anti-inflammatory feature and by activating the GABA pathway.

Exenatide, a GLP-1 analog, has healing effects on LPS-induced autism model: Inflammation, oxidative stress, gliosis, cerebral GABA, and serotonin interactions.

Previous studies have established anti-inflammatory, antioxidant, and neuroprotective effects of Exenatide in the central nervous system. Since these mechanisms are thought to have important roles in the pathophysiology of autism, we hypothesized that Exenatide may have healing effects in autism. We tested this hypothesis by examining the effects of Exenatide in an experimental autism model created by lipopolysaccharide (LPS) exposure in the womb, with behavioral tests, histopathological examinations, and biochemical measurements. The autism model was created by administration of LPS (i.p) to pregnant rats on the 10th day of their pregnancy at a dose of 100 µg/kg. On postnatal 21st day, a total of four groups were formed from offspring with regard to sex distribution and treatment. After a 45-day treatment, behavioral analysis tests were performed on rats. Subsequently, the rats were sacrificed and biochemical analysis [superoxide dismutase, tumor necrotizing factor alpha, nerve growth factor, 5-hydroxyindoleacetic acid, and glutamic acid decarboxylase-67] and histopathological analysis were performed. On the 10th day of the intrauterine period, LPS exposure was found to disrupt behavioral findings, increase inflammation and hippocampal gliosis, and decrease 5-HIAA, GAD-67, and NGF, especially in male rats. However, among the rats exposed to LPS in the intrauterine period, recipients of Exenatide demonstrated significant amelioration of findings. Exenatide therapy shows positive effects on behavioral disorders in an LPS-induced autism model. This agent probably exerts its effects by suppressing inflammation and oxidative stress and reducing hippocampal gliosis. In addition, Exenatide has also been shown to positively affect cerebral serotonergic and GABAergic effects.

Erythropoietin shows gender dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide induced rat model of autism.

We aimed to evaluate the effects of EPO in the lipopolysaccharide (LPS) induced rat model of autism in terms of social deficits, learning and memory impairments, as well as their neurochemical correlates. Sixteen female Sprague Dawley rats randomly distributed into two equel groups, then were caged with fertile males for mating. At the 10th day of pregnancy, 0.5 ml %0,9 NaCl saline was given to first group, 100 µg/kg LPS was given to second group to induce autism. On postnatal 21th day, forty-eight littermates were divided into four groups as; 8 male, 8 female controls, 16 male and 16 female LPS-exposed. Then, LPS groups were also divided in to two groups as saline (1 mg/kg/day) and EPO 600 U/kg/day groups, and animals were treated 45 days. At 50th day, after behavioral evaluations, brain levels of TNF-α, nerve growth factor (NGF) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed. Three-chamber sociability and social novelty test, passive avoidance learning test were revealed significant differences among the EPO and control groups. Histologically, hippocampal CA1 & CA3 regions displayed significant alterations regarding gliosis (GFAP-positive cells) and regarding frontal cortical thickness in EPO groups compare to controls. Biochemical measurements of the brain levels of TNF-α and NGF levels showed significant differences between controls and EPO groups. According to our findings EPO treatment has beneficial effects on ASD-like symptoms, learning and memory processes, neuronal loss and neuroinflammation in the LPS induced rat model of autism, with some gender differences through inflammatory and neurotrophic pathways.

Papaverine Has Therapeutic Potential for Sepsis-Induced Neuropathy in Rats, Possibly via the Modulation of HMGB1-RAGE Axis and Its Antioxidant Prosperities.

AIM: Our aim was to investigate the possible neuroprotective properties of papaverine in sepsis-induced critical illness neuropathy (SCIN) through the evaluation of various inflammatory biochemical markers, including interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), and oxidative stress biomarkers, such as malondialdehyde (MDA) and lactic acid. Additionally, evaluation of the HMGB1/RAGE interactions in SCIN was another target of this research. METHOD: To create a sepsis model, a procedure involving intraperitoneal injection of feces was performed on 48 rats. The rats were divided into four equal groups: sham operated, controls and those receiving 20 and 40 mg/kg/day papaverine. After five-day treatments, compound muscle action potential (CMAPs) with electroneuromyography (ENMG) was recorded in all rats. Following ENMG evaluations, the plasma levels of sRAGE, HMGB1, TNF-α, IL-6, CRP, MDA and lactic acid were measured. RESULTS: TNF-α, CRP, IL-6, HMGB1, MDA, and lactic acid levels were significantly elevated in the SCIN group, and sRAGE levels were significantly decreased. In recipients of papaverine (20 and 40 mg/kg) treatment, these biochemical findings were improved. Furthermore, electrophysiological findings also showed significant improvement in both 20 and 40 mg/kg papaverine treated groups. CONCLUSION: Papaverine demonstrates neuroprotective effects in a rat model of SCIN. Considering its anti-inflammatory and antioxidant properties, papaverine's neuroprotective effects possibly stem from the suppression of the RAGE-HMGB1 axis.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy.

INTRODUCTION: Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. OBJECTIVE - METHODS: Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. RESULTS: In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls (p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls (p < 0.001). CONCLUSION: We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.

Atorvastatin has therapeutic potential for the fatty liver-induced memory dysfunction in rats, likely via its antioxidant and anti-inflammatory properties.

This study aimed to evaluate the memory function in a rat model of fatty liver and to investigate the effects of statins on fatty liver, neuronal inflammation, oxidative stress and memory. In this study, 24 male rats were used and were divided into four groups consisting of 6 animals in each. Of them, 12 rats received liquid diet containing 35% fructose for 8 weeks in order to induce hepatosteatosis, while other animals had a normal nutrition. Group 1 served as controls and had a normal nutrition with no drug treatment. The animals in Group 2 had a normal nutrition and treated with atorvastatin. Group 3 received high-fructose diet with no drug treatment and Group 4 received high-fructose diet followed by atorvastatin treatment. After the two weeks of treatment period, passive avoidance tasks evaluating the memory were performed in both the study and control groups. The liver and brain were then removed for histologic, pathologic, and biochemical evaluation. In the non-treated rats with hepatosteatosis (Group 3), the lowest mean latency time and the highest mean histopathologic liver score, and brain TNF- α and MDA (Measurement of lipid peroxidation) were found (p < 0.00001). On the other hand, in the animals treated with atorvastatin, all these parameters were significantly higher than that of controls and significantly lower than that of Group 3 (p < 0.05). Fatty liver can increase inflammation and cause memory disorders, and atorvastatin may have a positive effect on cognitive disorders.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy

Abstract Introduction Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. Objective - methods Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. Results In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls ( p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls ( p < 0.001). Conclusion We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.(AU)

Do you have restless leg syndrome? I understood from your eyes.

PURPOSE: According to many studies in the literature, there is a strong association between restless leg syndrome and dopaminergic dysfunction. Dopamine is also the major catecholamine in the retina and is also a possible transmitter of the amacrine and interplexiform cells. The aim of this study is to investigate the possible association between RLS and retinal thickness. METHODS: In this study, we included 33 patients who were diagnosed with idiopathic RLS according to the "International RLS Study Group" criteria and 31 healthy subjects. All the patients and controls underwent routine ophthalmologic examination and had spectral-domain optical coherence tomography (OCT) performed. We compared the retinal thickness of the patients and control subjects. RESULTS: In the RLS group, foveal thickness was thinner then controls. Also, only inferior, superior, and temporal quadrant retina nerve fiber layer (RNFL) thickness were significantly thinner in the RLS group. The parafoveal ganglion cell complex (GCC) in the superior temporal, inferior temporal, inferior nasal quadrant, and perifoveal superior nasal thickness was also significantly thinner in the patient group. Pearson correlation analyses showed that there were statistically significant negative correlations between disease duration and macular GCC and RNFL thickness. Negative correlations were also detected between parafoveal superior, temporal, inferior and nasal macular thickness, parafoveal superior nasal, inferior temporal GCC thickness, and perifoveal superior nasal GCC thickness and disease duration. CONCLUSION: According to our results; most retinal layers are thinner in RLS patients, so it can be considered that OCT has a predictive value for progression of RLS.

Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy.

BACKGROUND: Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures. METHODS: Laboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ). RESULTS: Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant. CONCLUSIONS: Dapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.

Evaluation of the association between sexual dysfunction and demyelinating plaque location and number in female multiple sclerosis patients.

Purpose To investigate the frequency of sexual dysfunction (SD) in female multiple sclerosis (MS) patients and to explore its association with the location and number of demyelinating lesions. Material and Methods We evaluated 42 female patients and 41 healthy subjects. All patients underwent neurological examination and 1.5 T brain and full spinal MRI. All subjects completed the female sexual function index (FSFI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Short-Form 36 Quality of Life Scale (SF-36). All participants were also evaluated for serum thyroid stimulating hormone (TSH), T4, estradiol, and total testosterone. Results No statistically significant differences between the MS and control groups were found for age, body mass index (BMI), serum TSH, T4, E2, and total testosterone level. MS patients had a statistically significantly lower FSFI and SF-36 scores and higher BDI and BAI scores compared with healthy subjects. The location and number of demyelinating lesions were not associated with SD. Conclusion In our cohort, this difference in SD appears unrelated to the location and number of demyelinating lesions. These findings highlight the importance of the assessment and treatment of psychiatric comorbidities, such as depression and anxiety, in MS patients reporting SD.

Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study.

The aim of the present study was to compare the effects of artificial sweeteners (aspartame, saccharin, and sucralose) on rat brain. Twenty-four adult male Sprague-Dawley rats were included in the study. The control group (n = 6) received regular tap water, whereas other groups received aspartame (3 mg/kg/day, n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test was performed to evaluate the neurobehavioral effects of sweeteners. The brains were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake of sweeteners significantly impaired PAL performance in all groups. Hippocampal CA1-CA3 areas revealed significantly lower neuronal count in aspartame and increased GFAP expression in all groups. Brain lipid peroxides were significantly higher in all groups. Our findings suggest that long-term consumption of artificial sweeteners may have harmful effects on cognition and hippocampal integrity in rats.

Neuroprotective Effects of Eexenatide in a Rotenone-Induced Rat Model of Parkinson's Disease.

BACKROUND: Several studies suggest an association between Parkinson's disease (PD) and type 2 diabetes mellitus; these 2 diseases are both known to affect the common molecular pathways. As a synthetic agonist for the glucagon-like peptide 1 receptor, exenatide has been evaluated as a neuroprotective agent in multiple animal models. Rotenone models of PD have great potential for the investigation of PD pathology and motor and nonmotor symptoms, as well as the role of gene-environment interactions in PD causation and pathogenesis. Therefore, in this study, the neurochemical, behavioral and histologic effects of exenatide on a rotenone-induced rat model of PD were examined. MATERIALS AND METHODS: Eighteen adult male rats were randomly divided into the following 3 groups (n = 6): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1) and the others received stereotaxical infusion of rotenone (groups 2 and 3). Apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered exenatide for 28 days. RESULTS: Malondialdehyde and tumor necrosis factor alpha levels increased in the rats with PD induced by rotenone, whereas malondialdehyde and tumor necrosis factor alpha levels markedly decreased in the rats treated with exenatide. The apomorphine-induced rotation test scores of exenatide-treated rats were determined to be lower compared with the untreated group. Additionally, treatment with exenatide significantly reduced the loss of dopaminergic neurons in striatum. CONCLUSIONS: These results have shown that exenatide has neuroprotective, anti-inflammatory and antioxidant effects in a rotenone-induced rat model of PD.

Evaluation of Overactive Bladder in Male Antidepressant Users: A Prospective Study.

PURPOSE: In this study, we investigated overactive bladder (OAB) functions in male patients who used antidepressant drugs (ADs) that were previously examined in female patients, based on conflicting data in literature regarding the effects of AD on OAB and the differences between male and female urinary system physiologies (anatomical and hormonal). METHODS: The study included 202 male patients (a control group of 90 healthy subjects, and an experimental group of 112 patients taking ADs for different disorders). All the patients completed the overactive bladder-validated 8 (OAB-V8) questionnaire, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and the Beck Depression Inventory (BDS). RESULTS: The OAB-V8, ICIQ-SF, and BDS scores for the antidepressant users were significantly higher than those of the control group. The highest prevalence of OAB symptoms was observed in patients taking venlafaxine (68.2%), and the lowest prevalence was in patients taking sertraline (28.0%). Moreover, the frequency of OAB between the antidepressant groups was statistically significant. The univariate logistic regression analyses showed a significant relationship between the presence of OAB, antidepressant usage, BDS score, and the age of a patient. In the multivariate logistic regression analyses, the association between the presence of OAB and antidepressant usage was statistically significant. CONCLUSIONS: The present study showed that the incidence of OAB and the severity of OAB symptoms increased in males using antidepressants for various disorders. This may have been due to unique pharmacological effects, on a molecular or individual level, of serotonin-norepinephrine reuptake inhibitors.