Effect of l -Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role.

Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l -Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l -Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l -Dopa/benserazide administration in six groups (control, l -Dopa 25 mg/kg, l -Dopa 75 mg/kg, temozolomide, temozolomide +  l -Dopa 25 mg/kg, and temozolomide +  l -Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide +  l -Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l -Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l -Dopa antineuroinflammatory effects.

Gallic acid improves liver cirrhosis by reducing oxidative stress and fibrogenesis in the liver of rats induced by bile duct ligation.

Disturbance in the production and excretion of bile acid causes cholestatic liver disease. Liver cirrhosis is a disease that occurs if cholestasis continues. This study evaluated the protective effect of gallic acid (GA) on liver damage caused by biliary cirrhosis. Rats were randomly divided into 4 groups, each with 8 subjects: 1) control, 2) BDL, 3) BDL + GA 20, and 4) BDL + GA 30. The rats were anesthetized 28 days after the BDL, followed by collecting their blood and excising their liver. Their serum was used to measure liver enzymes, and the liver was used for biochemical analysis, gene expression, and histopathological analysis. Serum levels of liver enzymes, total bilirubin, liver Malondialdehyde level (MDA), expression of inflammatory cytokines and caspase-3, necrosis of hepatocytes, bile duct proliferation, lymphocytic infiltration, and liver fibrosis showed an increase in the BDL group compared to the control group (p < 0.05). In addition, BDL decreased the activity of liver antioxidant enzymes and glutathione (GSH) levels compared to the control group (p < 0.05). The groups receiving GA indicated a decrease in liver enzymes, total bilirubin, MDA, the expression of inflammatory cytokines and caspase-3, and a reduction in liver tissue damage compared to the BDL group (p < 0.05). The level of GSH in the BDL + GA 20 group showed a significant increase compared to the BDL group (p < 0.05). Moreover, it was found that GA, with its anti-fibrotic and anti-inflammatory properties, reduces liver damage caused by biliary cirrhosis.

Improving Swallowing Function and Ability in Post Stroke Dysphagia: A Randomized Clinical Trial.

Post-stroke dysphagia is a prevalent, life threatening condition. Scientists recommended implementing behavioral therapies with new technologies such as transcranial direct current of stimulation (TDCS). Studies showed promising TDCS effects, and scientists suggested the investigation of the effectiveness of different montages. Supramarginal gyrus (SMG) is important in swallowing function. Our study aimed to investigate the effectiveness of stimulating SMG in improving post-stroke dysphagia. Forty-four patients finished the study (a randomized, double-blind one). All of them received behavioral therapy. The real group received anodal (2 mA, 20 min) stimulation on the intact SMG, and the sham group received the same for 30 s (5 sessions). Patients were assessed with Functional Oral Intake Scale (FOIS) and Mann Assessment of Swallowing Ability (MASA) after treatment and at one-month follow-up. The results showed that the difference between groups at baseline was not significant. According to MASA both groups improved significantly during the time (p-value < 0.001). The improvement in the real group was significantly higher than in the sham group after treatment (p-value = 0.002) and after one-month follow-up (p-value < 0.001). According to FOIS, most of the patients in the real group (72.70%) reached level 6 or 7 after one-month follow-up which was significantly higher than the sham group (31.80%, p-value = 0.007). In conclusion, TDCS applied to the scalp's surface associated with SMG localization may improve swallowing function in the stroke patients with dysphagia.

Effect of High-Intensity Interval Training on Cardiac Apoptosis Markers in Methamphetamine-Dependent Rats.

Chronic methamphetamine use increases apoptosis, leading to heart failure and sudden cardiac death. Previous studies have shown the importance of high-intensity interval training (HIIT) in reducing indices of cardiac tissue apoptosis in different patients, but in the field of sports science, the molecular mechanisms of apoptosis in methamphetamine-dependent rats are still unclear. The present article aimed to investigate the changes in cardiac apoptosis markers in methamphetamine-dependent rats in response to HIIT. Left ventricular tissue was used to evaluate caspase-3, melusin, FAK, and IQGAP1 gene expression. Rats were divided into four groups: sham, methamphetamine (METH), METH-control, and METH-HIIT. METH was injected for 21 days and then the METH-HIIT group performed HIIT for 8 weeks at 5 sessions per week. The METH groups showed increased caspase-3 gene expression and decreased melusin, FAK, and IQGAP1 when compared to the sham group. METH-HIIT showed decreased caspase-3 and increased melusin and FAK gene expression compared with the METH and METH-control groups. The IQGAP1 gene was higher in METH-HIIT when compared with METH, while no difference was observed between METH-HIIT and METH-control. Twenty-one days of METH exposure increased apoptosis markers in rat cardiac tissue; however, HIIT might have a protective effect, as shown by the apoptosis markers.

Induction of cross-tolerance between protective effect of morphine and nicotine in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells.

PURPOSE: Parkinson's disease is a progressive neurodegenerative disease characterized by progressive and selective death of dopaminergic neurons. It has been reported that nicotine and morphine have protective roles during neuronal damage in Parkinson's disease. In addition, the induction of cross-tolerance between their biological effects has been shown in numerous reports. METHODS: Here, we investigated the effects of nicotine and morphine on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 µM 6-OHDA and the cells viability was examined by MTT assay. Intracellular reactive oxygen species, calcium level, and mitochondrial membrane potential were determined by fluorescence spectrophotometer method. Biochemical markers of apoptosis were also evaluated by immunoblotting. RESULT: The data showed that morphine and nicotine prevent 6-OHDA- induced cell damage and apoptosis. However, the protective effects of nicotine were not observed in chronic morphine-pretreated cells. Morphine had no protective effects in chronic nicotine-incubated cells. CONCLUSION: A cross-tolerance between protective effects of morphine and nicotine was occurred in 6-OHDA-induced SH-SY5Y cell toxicity.

Functional Antagonism of Sphingosine-1-Phosphate Receptor 1 Prevents Harmaline-Induced Ultrastructural Alterations and Caspase-3 Mediated Apoptosis.

BACKGROUND: There is a meaningful necessity for a targeted therapy of essential tremor (ET), as medications have not been developed specifically for ET. For nearly a century, many drugs have been applied in the treatment of tremor but the drug treatment of ET remains still unknown. Some potential therapeutic factors such fingolimod (FTY720) can be effectively used to treat ET in animals. In the present research, the effect of FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, on degeneration of cerebellar and olivary neurons induced by harmaline in male rats was investigated. METHODS: The animals were allotted into control dimethyl sulfoxide (DMSO), saline + harmaline [30 mg/kg, intraperitoneally, (i.p.)], harmaline + FTY720 (1 mg/kg, i.p, 1 h and 24 h before harmaline injection) groups (n = 10). The cerebellum and inferior olive nucleus (ION) were studied for neuronal degeneration using immunohistochemistry (IHC) and ultrastructural study by transmission electron microscopy (TEM) techniques. RESULTS: Harmaline caused neuronal cell loss, caspase-3 mediated apoptosis, astrocytosis and ultrastructural changes in cerebellar Purkinje cells and inferior olive neurons. FTY720 exhibited neuroprotective effects on cerebellar Purkinje cells and inferior olivary neurons. CONCLUSION: These results suggest that FTY720 has potential efficacy for prevention of ET neurodegeneration and astrocytosis induced by harmaline in male rats.

Spatial memory recovery in Alzheimer's rat model by electromagnetic field exposure.

INTRODUCTION: Although studies have shown a potential association between extremely low frequency electromagnetic fields (ELF-EMFs) exposure and Alzheimer's disease (AD), few studies have been conducted to investigate the effects of weak magnetic fields on brain functions such as cognitive functions in animal models. Therefore, this study aimed to investigate the effect of ELF-EMF exposure (50 Hz, 10 mT) on spatial learning and memory changes in AD rats. METHODS: Amyloid-ß (Aß) 1-42 was injected into lateral ventricle to establish an AD rat model. The rats were divided into six groups: Group I (control); Group II (surgical sham); Group III (AD) Alzheimer's rat model; Group IV (MF) rats exposed to ELF-MF for 14 consecutive days; Group V (Aß injection+M) rats exposed to magnetic field for 14 consecutive days from day 0 to 14 days after the Aß peptide injection; Group VI (AD+M) rats exposed to magnetic field for 14 consecutive days after 2 weeks of Aß peptide injection from 14th to 28th day . Morris water maze investigations were performed. RESULTS: AD rats showed a significant impairment in learning and memory compared to control rats. The results showed that ELF-MF improved the learning and memory impairments in Aß injection+M and AD+M groups. CONCLUSION: Our results showed that application of ELF-MF not only has improving effect on different cognitive disorder signs of AD animals, but also disrupts the processes of AD rat model formation.

A Trial Study of Static Telepathology in Iran.

Static telepathology is one of the telepathology methods, in which the captured images of the slides are transmitted for consultation at a later time. This study aimed to compare the diagnostic accuracy of the conventional pathology and static telepathology systems. Eighty-two cases that had been selected randomly from 4 pathology centers in the city of Kerman were diagnosed by a pathologist, first based on light microscopy and then after 2 months based on static images (2 images per case) captured by a Nikon 50i microscopic camera. The images were sent to the pathologist via e-mail. The diagnostic accuracy of the telepathology system was calculated. The light microscopic diagnoses were concordant with the telepathologic diagnoses in 71 of 82 reviewed cases. Different diagnoses of 7 cases were due to the images captured from the inappropriate location of the slides. The diagnostic accuracy of the telepathology system was 86.5%. The results of this study showed that static telepathology is very accurate and can be widely used in Iran. However, efficient implementation and use of telepathology require paying attention to different issues such as educational, legal, ethical, financial, and security and observance of the standards related to this field.

Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1ß Proteins in a Rat Model of Cerebral Ischemia.

BACKGROUND: Nepeta dschuparensis Bornm (NP) is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2) and interleukin-1ß (IL-1ß) protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. METHODS: Twenty-six male rats were randomly divided into 3 groups: 1) sham (n=6): no middle cerebral artery occlusion (MCAO) procedure, 2) control (n=10): MCAO procedure and treatment with normal saline, and 3) NP extract (n=10): MCAO procedure and treatment with the NP extract (20 mg/kg, i.p.) at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1ß and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01). RESULTS: Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1ß and COX-2 protein levels too (P<0.01). CONCLUSION: The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1ß and COX-2.

The promising effect of barberry (Zereshk) extract against experimental pulmonary microvascular remodeling and hypertension: A comparison with sildenafil.

CONTEXT: Despite the beneficial effects of barberry (Berberis integerrima Berberidaceae) on decreasing systemic hypertension, its influence has not been investigated on pulmonary hypertension. OBJECTIVE: The objective of this study is to examine the effect of barberry fruit, on monocrotaline-induced pulmonary hypertension. MATERIALS AND METHODS: Nine groups were arranged as follows: the control group, the monocrotaline (M) group, the barberry groups with doses of 50, 100, and 200 (mg/kg), the M plus barberry groups, and the M plus sildenafil group. Two weeks after a single injection of monocrotaline (60 mg/kg, s.c.), barberry water extracts or sildenafil (30 mg/kg/d) were gavaged daily for 2 weeks. At the end of the 4th week, hemodynamic, biochemical, and histopathological parameters were assessed. RESULTS: In comparison with the M group, barberry (200 mg/kg) or sildenafil significantly reduced the right ventricular systolic pressure (RVSP) (22.95 ± 1.78 mm Hg and 30.71 ± 1.64 mm Hg, versus 41.28 ± 1.5 mm Hg), right ventricular hypertrophy (RVH) (0.39 ± 0.03 and 0.42 ± 0.02, versus 0.57 ± 0.02), and the medial wall thickness (MWT) (4.56 ± 0.15 µm and 5.97 ± 0.19 µm, versus 7.02 ± 0.43 µm). Barberry or sildenafil had no significant effect on the plasma level of endothelin-1, glutathione peroxidase, and the malondialdehide of lung. CONCLUSION: 200 mg/kg of barberry has an improving effect on the monocrotaline-induced pulmonary hypertension. This effect was stronger than that of the sildenafil's and may have been mediated through mechanisms other than the modulation of the endothelin-1 or redox system.

The effect of Angipars on diabetic neuropathy in STZ-induced diabetic male rats: a study on behavioral, electrophysiological, sciatic histological and ultrastructural indices.

Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1 mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20 mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats.

Potential mechanisms involved in the anticonvulsant effect of walnut extract on pentylenetetrazole-induced seizure.

OBJECTIVE: It was the aim of this study to determine the potential effect of walnut kernel extract (WKE) on experimentally induced seizures in rats and to evaluate the role of benzodiazepines and ethosuximide (ESM) within these pathways. MATERIALS AND METHODS: Male Wistar rats were selected and divided into eight groups. Seizures were evoked by intravenous infusion of pentylenetetrazole (PTZ; 2 mg/ml/min). In combination with PTZ, animals were treated with vehicle or WKE (100 mg/kg i.p.), with or without cotreatment with either flumazenil (FMZ; 5 mg/kg i.p.), ESM (150 mg/kg i.p.) or diazepam (DPZ; 0.5 mg/kg i.p.). RESULTS: WKE administration significantly increased the PTZ dose needed to induce the first myoclonic jerk (13.09 ± 1.29 vs. 49.71 ± 12.03 mg/kg; p < 0.001), decreased the severity of seizure grades and reduced the mortality rate to 0%. FMZ did not significantly reduce the anticonvulsant effect of WKE. The combination of DPZ and WKE showed a synergic anticonvulsant effect, whereas ESM had no significant influence (p > 0.05) on the WKE effects. CONCLUSION: These findings indicated that WKE was effective at reducing seizure severity, at increasing the dose to the first myoclonic jerk and highly efficacious at preventing mortality, because 100% of animals were protected. It seems that this positive effect could apply through signaling pathways other than benzodiazepine-mediated γ-aminobutyric acid receptors and may at least in part be similar to ESM.

Resveratrol and 1,25-dihydroxyvitamin D decrease Lingo-1 levels, and improve behavior in harmaline-induced Essential tremor, suggesting potential therapeutic benefits.

Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.

Agmatine improves liver function, balance performance, and neuronal damage in a hepatic encephalopathy induced by bile duct ligation.

INTRODUCTION: In the current study, we investigate whether oral administration of agmatine (AGM) could effectively reduce motor and cognitive deficits induced by bile duct ligation (BDL) in an animal model of hepatic encephalopathy (HE) through neuroprotective mechanisms. METHODS: The Wistar rats were divided into four groups: sham, BDL, BDL+ 40 mg/kg AGM, and BDL+ 80 mg/kg AGM. The BDL rats were treated with AGM from 2 weeks after the surgery for 4 consecutive weeks. The open field, rotarod, and wire grip tests were used to assess motor function and muscle strength. The novel object recognition test (NOR) was performed to evaluate learning and memory. Finally, blood samples were collected for the analysis of the liver markers, the animals were sacrificed, and brain tissues were removed; the CA1 regions of the hippocampus and cerebellum were processed to identify apoptosis and neuronal damage rate using caspase-3 immunocytochemistry and Nissl staining. RESULTS: The serological assay results showed that BDL severely impaired the function of the liver. Based on histochemical findings, BDL increased the neuronal damage in CA1 and Purkinje cells, whereas apoptosis was significantly observed only in the cerebellum. AGM treatment prevented the increase of serum liver enzymes, balance deficits, and neuronal damage in the brain areas. Apoptosis partially decreased by AGM, and there were no differences in the performance of animals in different groups in the NOR. CONCLUSIONS: The study suggests AGM as a potential treatment candidate for HE because of its neuroprotective properties and/or its direct effects on liver function.

The role of transcranial direct current stimulation in diminishing the risk of pneumonia in patients with dysphagia: A double-blinded randomized clinical trial.

Background: Dysphagia can be a life-threatening issue for post-stroke patients, with aspiration pneumonia (AP) being a common risk. However, there is hope through the potential combination of transcranial direct current stimulation (tDCS) and classical behavior therapy. Our study aims to investigate the effectiveness of this combination in diminishing the risk of AP in patients with dysphagia who suffered from stroke. Methods: In this randomized, parallel-group, blinded clinical trial, 48 patients were allocated into the sham group (speech therapy + 30 seconds of tDCS) and the real group (speech therapy + 20 minutes of tDCS). We used the Mann Assessment of Swallowing Ability (MASA) as an assessment tool. We assessed patients at baseline, one day after treatment, and at a one-month follow-up. Results: Groups showed no significant difference at baseline. After treatment, the real group showed a significant difference in the severity risk of AP (P = 0.02); the same was for the follow-up (P = 0.04). The number of patients showing severe risk of AP was higher in the sham group after treatment (n = 13, 54.20%) and at follow-up (n = 4, 18.20%) than the real group (n = 4, 16.70%; n = 1, 4.50%, respectively). None of the patients reported the history of AP at any stage of assessment. Conclusion: Although the results were more promising in the real group than the sham group in reducing the risk of AP, both techniques can prevent AP. Therefore, we recommend early dysphagia management to prevent AP regardless of the treatment protocol.

Impact of ketamine administration on chronic unpredictable stress-induced rat model of depression during extremely low-frequency electromagnetic field exposure: Behavioral, histological and molecular study.

OBJECTIVES: In the study, we examined the effects of ketamine and extremely low-frequency electromagnetic fields (ELF-EMF) on depression-like behavior, learning and memory, expression of GFAP, caspase-3, p53, BDNF, and NMDA receptor in animals subjected to chronic unpredictable stress (CUS). METHODS: After applying 21 days of chronic unpredictable stress, male rats received intraperitoneal (IP) of ketamine (5 mg/kg) and then were exposed to ELF-EMF (10-Hz, 10-mT exposure conditions) for 3 days (3 h per day) and behavioral assessments were performed 24 h after the treatments. Instantly after the last behavioral test, the brain was extracted for Nissl staining, immunohistochemistry, and real-time PCR analyses. Immunohistochemistry (IHC) was conducted to assess the effect of ketamine and ELF-EMF on the expression of astrocyte marker (glial fibrillary acidic protein, GFAP) in the CA1 area of the hippocampus and medial prefrontal cortex (mPFC). Also, real-time PCR analyses were used to investigate the impacts of the combination of ketamine and ELF-EMF on the expression of caspase3, p53, BDNF, and NMDA receptors in the hippocampus in rats submitted to the CUS procedure. Results were considered statistically significant when p < .05. RESULTS: Our results revealed that the combination of ketamine and ELF-EMF increased depression-like behavior, increased degenerated neurons and decreased the number of GFAP (+) cells in the CA1 area and mPFC, incremented the expression of caspase-3, and reduced the expression of BDNF in the hippocampus but showed no effect on the expression of p53 and NMDA-R. CONCLUSIONS: These results reveal that combining ketamine and ELF-EMF has adverse effects on animals under chronic unpredictable stress (CUS).

Naringenin mitigates reserpine-induced anxiety-like behavior, neurodegeneration, and oxidative stress in male rats.

Reserpine (Res) induces anxiety-like behaviors, orofacial dyskinesia, and neurodegeneration in animals, the pathophysiology of which has been related to oxidative stress. The purpose of this study was to investigate whether naringenin (NG) could prevent reserpine-induced anxiety-like behaviors, orofacial dyskinesia, and neurodegeneration in male rats. Twenty-eight male rats were distributed into different groups as follows: Control rats; vehicle rats, which received the vehicles (normal saline, orally; acetic acid, intraperitoneally); Res rats (1 mg/kg/day) every other day for 3 days; and Res + NG rats, which received NG (50 mg/kg, orally, pre-treatment for 7 days), followed by Res. Administration of Res significantly increased chewing frequency compared with the control group (P < 0.01) and NG reversed the effect of Res on this factor (P < 0.05). Res induced an anxiety-like behavior in rats in the plus maze, and pre-treatment with NG improved this behavior. In addition, Res significantly increased the level of oxidative stress markers and degenerated neurons in the striatum; NG was able to ameliorate these damages. The results of this study demonstrated that Res caused behavioral disorders and increased the levels of oxidative stress in male rats; the use of NG was effective in treating these disorders. Therefore, NG should be considered as a preventive agent for reserpine-induced brain damage in male rats.

Profound destructive effects of adolescent exposure to vincristine accompanied with some sex differences in motor and memory performance.

Vincristine, an anticancer drug, is known to induce neuronal cell damage. We have elucidated the alteration in performance of the hippocampus and cerebellum following chronic vincristine treatment (0.2 mg·(kg body mass)(-1)·week(-1)) in male and female rats. Intraperitoneal injection of vincristine in adolescent rats caused impairment of motor and cognitive behavior. In the probe test, the length of path traveled and percent swimming time for vincristine-treated rats in the correct quadrant was significantly less than for the saline-treated (control) groups. The path length and time latency at the 2nd and 3rd blocks of trials for the male vincristine-treated group was significantly higher than that for the female saline- and the vincristine-treated rats. In the rod test, vincristine exposure impaired the motor coordination in both male and female rats. Exposure to vincristine caused a significant decrease in hanging time in male rats, compared with the saline- and the vincristine-treated female rats, while there were no differences between the female vincristine-treated rats and the saline-treated rats of both sexes. The rearing frequency, total distance moved, and velocity for both male and female rats were dramatically affected by exposure to vincristine. We have observed that the hippocampal and cerebellar functions of male and female rats were profoundly affected by exposure to vincristine, especially the male rats, suggesting a sexual dimorphism in the developing central nervous system that is affected by chemicals such as anticancer drugs.

The role of adenosine receptor agonist and antagonist on Hippocampal MDMA detrimental effects; a structural and behavioral study.

There is abundant evidence showing that repeated use of MDMA (3, 4-Methylenedioxymethamphetamine, ecstasy) has been associated with depression, anxiety and deficits in learning and memory, suggesting detrimental effects on hippocampus. Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. In the present study, we investigated the role of A2a adenosine receptors agonist (CGS) and antagonist (SCH) on the body temperature, learning deficits, and hippocampal cell death induced by MDMA administration. In this study, 63 adult, male, Sprague - Dawley rats were subjected to MDMA (10 and 20 mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03 mg/kg) injection. The animals were tested for spatial learning in the Morris water maze (MWM) task performance, accompanied by a recording of body temperature, electron microscopy and stereological study. Our results showed that MDMA treatment increased body temperature significantly, and impaired the ability of rats to locate the hidden platform(P < 0.05). The number of hippocampal dark neurons also increased especially in CA1. These impairments were aggravated by co-administration of A2a antagonist (SCH) with MDMA. Furthermore, the administration of the A2a receptor agonist (CGS) provided partial protection against MWM deficits and hippocampal cell death(P < 0.05). This study provides for the first time evidence that, in contrast to A2a antagonist (SCH) effects, co-administration of A2a agonist (CGS) with MDMA can protect against MDMA hippocampal neurotoxic effects; providing a potential value in the prevention of learning deficits observed in MDMA users. However, the exact mechanism of these interactions requires further studies.

Chronically Pre-treatment of Pistachio Alters the Morphology of CA1 Hippocampus Neurons Following Transient Focal Cerebral Ischemia in Male Wistar Rats.

BACKGROUND: Consumption of antioxidants is effective on reducing the damage caused by cerebral ischemia. OBJECTIVES: We investigated the effect of Pistacia vera (pistachio) pretreatment on the morphology of the cornu ammonis (CA1) region of hippocampus neurons of the rats' hippocampus following transient focal cerebral occlusion of the middle cerebral artery (MCA). METHODS: In this study, 30  male Wistar rats were divided into 3 groups of control, ischemia, and pretreatment with pistachio (fed with pistachio at 6% of the diet for a five-week duration before the right MCA occlusion). Neurological scores of the rats were assessed using Baderson rating. Thereafter, the animals' balance and muscle power were assessed by Rotarod and forelimb wire-grip strength tests, respectively. Finally, histopathological and morphometrical characteristics of hippocampal neurons were studied using Hematoxylin-Eosin method. RESULTS: Neurological scores of the ischemia group significantly decreased compared to the control group (p<0.05), while pretreatment with pistachio significantly improved Baderson rating scores compared to the ischemia group (p<0.05). Although stroke significantly decreased the balance and muscular strength in the studied rats compared to the normal rats (p<0.05), pistachio's exposure significantly increased the balance and muscular strength compared to the ischemia group (p<0.05). Additionally, a significant decrease was observed in the volume of stroke and neuronal degradation in the pistachio-treated rats compared with the ischemia group (p<0.05). CONCLUSIONS: Pistachio consumption reduces the volume of infarction and neuronal damage and improves neurological disorders after ischemia. Therefore, pretreatment with pistachio would have a protective effect against stroke.