Art-based assignment in head and neck anatomical course, a dynamic experience.

In recent years, alternative uses of art within medical education have been explored and extended. We report here a method of art-based assignments in anatomy and histology, which we have incorporated into the head and neck course as a means of enlivening didactic lectures. One hundred and two first-year medical students at the Alborz University of Medical Sciences participated in a 15-week educational intervention, in which an art-based assignment method was employed. The learning module focuses on the human anatomy and histology of head and neck. In each session, after the teacher's lecture and practical work, students were given an assignment based on the topics of that session and based on the drawing. The learning outcome was evaluated twice, 1 week and 4 weeks after the course. Student's feedbacks were collected via an anonymous questionnaire at the end of the module. The data were analyzed by using the SPSS 20 software by paired and independent t-tests and the normality of data was evaluated by the Kolmogorov-Smirnov test. Most of students (90%) had rated the new format as very informative. Exam scores were significantly higher at 4 weeks tests (P ≤ 0.05) and data showed significant difference in long-term retention of knowledge. The use of this module by medical students during their head and neck course improves their confidence through drawing. Teacher's feedback provides a step-wise approach that simplifies the learning of anatomy and histology. The strategy has appeal for visual, auditory, read/write, and kinesthetic learners.

In-hospital mortality rate in subaxial cervical spinal cord injury patients: a systematic review and meta-analysis.

PURPOSE: To determine existing trends concerning in-hospital mortality in patients with traumatic subaxial cervical spinal cord injury (SCI) over the last four decades. METHODS: We searched MEDLINE and EMBASE to assess the role of the following factors on in-hospital mortality over the last four decades: neurological deficit, age, surgical decompression, use of computed tomography (CT) and magnetic resonance imaging (MRI), use of methylprednisolone in the acute post-injury period, and study location (developing versus developed countries). RESULTS: Among 3333 papers after deduplication, 21 studies met the eligibility criteria. The mortality rate was 17.88% [95% confidence interval (CI): 12.9-22.87%]. No significant trend in mortality rate was observed over the 42-year period (meta-regression coefficient = 0.317; p = 0.372). Subgroup analysis revealed no significant association between acute subaxial cervical SCI-related mortality when stratified by use of surgery, administration of methylprednisolone, use of MRI and CT imaging, study design (prospective versus retrospective study), and study location. The mortality rate was significantly higher in complete SCI (20.66%, p = 0.002) and American Spinal Injury Association impairment scale (AIS) A (20.57%) and B (9.28%) (p = 0.028). CONCLUSION: A very low level of evidence showed that in-hospital mortality in patients with traumatic subaxial cervical SCI did not decrease over the last four decades despite diagnostic and therapeutic advancements. The overall acute mortality rate following subaxial cervical SCI is 17.88%. We recommend reporting a stratified mortality rate according to key factors such as treatment paradigms, age, and severity of injury in future studies.

Association between colorectal cancer and expression levels of miR-21, miR-17-5P, miR-155 genes and the presence of Fusobacterium nucleatum in biopsy samples obtained from Iranian patients.

BACKGROUND: Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC. METHOD: DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group. CONCLUSION: Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes.

Effects of Au@Ag core-shell nanostructure with alginate coating on male reproductive system in mice.

Despite the widespread use of silver nanoparticles (NPs), these NPs can accumulate and have toxic effects on various organs. However, the effects of silver nanostructures (Ag-NS) with alginate coating on the male reproductive system have not been studied. Therefore, this study aimed to investigate the impacts of this NS on sperm function and testicular structure. After the synthesis and characterization of Ag-NS, the animals were divided into five groups (n = 8), including one control group, two sham groups (received 1.5 mg/kg/day alginate solution for 14 and 35 days), and two treatment groups (received Ag-NS at the same dose and time). Following injections, sperm parameters, apoptosis, and autophagy were analyzed by the TUNEL assay and measurement of the mRNA expression of Bax, Bcl-2, caspase-3, LC3, and Beclin-1. Fertilization rate was assessed by in vitro fertilization (IVF), and testicular structure was analyzed using the TUNEL assay and hematoxylin and eosin (H&E) staining. The results showed that the NS was rod-shaped, had a size of about 60 nm, and could reduce sperm function and fertility. Gene expression results demonstrated an increase in the apoptotic markers and a decrease in autophagy markers, indicating apoptotic cell death. Moreover, Ag-NS invaded testicular tissues, especially in the chronic phase (35 days), resulting in tissue alteration and epithelium disintegration. The results suggest that sperm parameters and fertility were affected. In addition, NS has negative influences on testicular tissues, causing infertility in men exposed to these NS.

Effect of Olibanum Extract/Graphene Oxide on Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells on Freeze Dried Scaffolds.

Background: One of the challenges in using stem cells to neural repair is to induce their differentiation into neurons and lack of glial formation. Objectives: Mesenchymal stem cells have revealed great potential for neural reorganization and renewal by taking advantage of differentiation capabilities. Here we explored the potential use of olibanum extract in freeze-dried scaffolds for induction of stem cells differentiation. Materials and Methods: In this study, gelatin/ collagen/olibanum/ graphene oxide (GEL/COL/OL/GO) freeze-dried scaffolds were synthesized and then adult rat bone marrow mesenchymal stem cells (BMMSCs) were seeded on scaffolds. The viability of cells was evaluated using MTT test on days 1, 3 and 5. The morphology of the cells seeded on scaffolds was studied using SEM and specific protein expression detected by immunohistochemical analysis. Real-time PCR was applied to detect the expression of Chat, Pax6, Hb-9, Nestin, Islet-1, and neurofilament-H (NF-H). The data were analyzed using Tukey test and one-way ANOVA and the means difference was considered significant at P<0.05, P<0.01, and P<0.001. Results: Showed that the pore size is increased in GEL/COL/OL/GO scaffolds compared with GO-free scaffolds and higher attachment and proliferation of BMMSCs on GEL/COL/OL /1.5% GO scaffolds compared to GEL/COL/OL/3% GO scaffolds. The cell viability results after 5 days of incubation showed the significant biocompatibility of GEL/COL/OL /1.5% GO freeze-dried scaffold. The results of immunohistochemical and PCR analysis revealed positive role of GEL/COL/OL/1.5% GO scaffolds in upregulation of neuron-specific markers. Conclusion: These results reveal the great potential of GEL/COL/OL/GO scaffolds for nerve regeneration. Our data suggested that both OL extract and GO can regulate the MSCs differentiation into neurons.

MDMA related neuro-inflammation and adenosine receptors.

3,4-methylenedioxymethamphetamine (MDMA) is a world-wide abused psychostimulant, which has the neurotoxic effects on dopaminergic and serotonergic neurons in both rodents and non-human primates. Adenosine acts as a neurotransmitter in the brain through the activation of four specific G-protein-coupled receptors and it acts as a neuromodulator of dopamine neurotransmission. Recent studies suggest that stimulation of adenosine receptors oppose many behavioral effects of methamphetamines. This review summarizes the specific cellular mechanisms involved in MDMA neuroinflammatory effects, along with the protective effects of adenosine receptors.

The Anti-Helicobacter pylori Effects of Lactobacillus acidophilus, L. plantarum, and L. rhamnosus in Stomach Tissue of C57BL/6 Mice.

BACKGROUND AND AIM: Helicobacter pylori is one of the most common pathogenic bacteria in the human gut, and is also one of the most important factors that cause digestive disorders such as chronic inflammation, gastric ulcers, and even gastric cancer. Since the use of various antibiotics to treat H. pylori infection is associated with the development of resistance in this bacterium, the aim of this study was to determine the anti-H. pylori effects of Lactobacillus acidophilus, L. plantarum, and L. rhamnosus in the stomach tissue of C57BL/6 mice. MATERIALS AND METHODS: In this experimental study, 70 mice in ten groups were evaluated from July to September 2017 in the microbiology laboratory of the School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. After induction of H. pylori infection in mice with the standard strain of H. pylori (ATCC 43504), the infected mice were treated with drug and Lactobacillus species in different groups. Then, the anti-H. pylori effects of lactobacilli were evaluated by stool antigen test and tissue staining. RESULTS: Based on ELISA results and histological findings, a reduction of inflammation was observed. The group which was only exposed to L. rhamnosus and the one which was exposed to all three strains of Lactobacillus showed the highest antimicrobial effect on H. pylori. CONCLUSION: According to the results of this study, probiotic bacteria including L. acidophilus, L. plantarum, and L. rhamnosus could be useful in the reduction of H. pylori infection in the mouse model.

A bioinspired 3D shape olibanum-collagen-gelatin scaffolds with tunable porous microstructure for efficient neural tissue regeneration.

There are a number of procedures for regeneration of injured nerves; however, tissue engineering scaffolds seems to be a promising approach for recovery of the functionality of the injured nerves. Consequently, in this study, olibanum-collagen-gelatin scaffolds were fabricated by freeze-cast technology. For this purpose, the olibanum and collagen were extracted from natural sources. The effect of solidification gradient on microstructure and properties of scaffolds was investigated. Scanning electron microscopy micrographs showed the formation of lamellar-type microstructure in which the average pore size reduced with an increase in freezing rate. According to the results, the prepared scaffolds at lower freezing rate showed a slight reduction in mechanical strength while the swelling and biodegradation ratio were increased due to the presence of larger pores and unidirectional channels. The composition of scaffolds and oriented microstructure improved cellular interaction. In addition, scaffolds with lower freezing rate exhibited promising results in terms of adhesion, spreading, and proliferation. In brief, the synthesized scaffolds at lower solidification rate have the potential for more in vitro and in vivo analyses to regeneration of neural defects.

Filtered Kombucha tea ameliorates the leaky gut syndrome in young and old mice model of colitis.

OBJECTIVES: Zonula occludens proteins (ZO-1 and ZO-2) are important intracellular tight junction (TJ)-associated proteins that link the cell cytoskeleton to the trans-membrane TJ proteins. Destruction of TJ proteins is called the "leaky gut syndrome" and has been observed in some of the gastrointestinal diseases such as the inflammatory bowel disease (IBD). So, therapeutic approaches aim to restore the expression of TJ proteins and reduce intestinal permeability. Healing effect of Kombucha tea (KT), so-called long-life mushroom, on the gastrointestinal system, particularly its extraordinary healing effects on intestinal ulcers has been purported traditionally and rarely reported scientifically. This study aimed to investigate the therapeutic effect of filtered KT (fKT) in young and old mice model of colitis. MATERIALS AND METHODS: Leaky gut was induced in two groups of young and old age using dextran sodium sulfate in drinking water for seven days. Then, fKT was administered to the mice affected by colitis and compared with the age-matched normal and untreated animals with colitis. RESULTS: Survival rate of the fKT-treated young and old animals with colitis increased and weight loss decreased. Accordingly, digestive disorders characterized by bleeding and diarrhea were improved in fKT-treated mice. Molecular and histological examination indicated that expression of ZO-1 and ZO-2 was significantly improved in fKT-treated mice. CONCLUSION: Our results suggest KT as a promising therapeutic candidate to reduce intestinal permeability. Young animals with colitis showed more severe clinical signs and less survival rate than old mice with colitis, but this group responded better to fKT treatment than the old mice.

HONEY-DERIVED LACTOBACILLUS RHAMNOSUS ALLEVIATES HELICOBACTER PYLORI-INDUCED GASTRO-INTESTINAL INFECTION AND GASTRIC INFLAMMATION IN C57BL/6 MICE: AN IMMUNO-HISTOLOGIC STUDY.

BACKGROUND: Helicobacter pylori (H. pylori) has been introduced by since 1983 by Marshal and Warren to play the main role in the pathophysiology of gastritis and gastric ulcers. Almost half of the world population1 is infected by H. pylori. Current therapeutic regimen against H. pylori includes the use of a proton pump inhibitor plus two or more antibiotics. However, the efficacy of this regimen is decreasing mainly due to antibiotic resistance and side effects of medications. This fact has resulted in public interest in other therapeutic options and the role of probiotics merits special attention in this regard. OBJECTIVE: This study aims to evaluate the efficacy of honey-derived Lactobacillus rhamnosus on H. pylori-induced gastric inflammation and gastro-intestinal infection in C57BL/6 Mice. METHODS: The 24 C57BL/6 Mice were randomly divided into three groups of eight mice each. All the mice were fed with 1cc suspension containing 5*1010 CFU/ mL of ATCC43504 strains of H. pylori for 3 consecutive days, twice daily via polyethylene gavage tubes. At the end of 4th week, infection with H. pylori was confirmed with stool Ag (ELISA) and following sacrifice of one mouse from each group, histopathologic study confirmed gastritis. The groups were subjected to different therapies as stated, 1: without Bismuth (Bi), Omeprazole (Om) and L. rhamnosus prescription, 2: Bi, Om and Clarithromycin (Cl) and 3: Bi, Om plus 1cc of suspension of 109 CFU/mL of L. rhamnosus. After 2 weeks, the stool was analyzed for Ag and the mice were sacrificed for evaluation of histopathologic changes. RESULTS: Treatment with L. rhamnosus group provided Zero titer of stool Ag and was associated with improved gastric inflammation in all subjects, similar to the clarithromycin group. CONCLUSION: Honey-derived L. rhamnosus probiotics provides similar results as clarithromycin in terms of improvement of H. pylori infection and gastritis in C57BL/6 Mice model, without its cons of antibiotic resistance.

O mel-derivado de Lactobacillus rhamnosus alivia a infecção gastro-intestinal induzida pelo Helicobacter pylori-e inflamação gástrica em C57Bl/6 ratos: um estudo imuno-histológico / Honey-derived lactobacillus rhamnosus alleviates helicobacter pylori-induced gastro-intestinal infection and gastric inflammation in c57bl/6 mice: an immuno-histologic study

ABSTRACT BACKGROUND: Helicobacter pylori (H. pylori) has been introduced by since 1983 by Marshal and Warren to play the main role in the pathophysiology of gastritis and gastric ulcers. Almost half of the world population1 is infected by H. pylori. Current therapeutic regimen against H. pylori includes the use of a proton pump inhibitor plus two or more antibiotics. However, the efficacy of this regimen is decreasing mainly due to antibiotic resistance and side effects of medications. This fact has resulted in public interest in other therapeutic options and the role of probiotics merits special attention in this regard. OBJECTIVE: This study aims to evaluate the efficacy of honey-derived Lactobacillus rhamnosus on H. pylori-induced gastric inflammation and gastro-intestinal infection in C57BL/6 Mice. METHODS: The 24 C57BL/6 Mice were randomly divided into three groups of eight mice each. All the mice were fed with 1cc suspension containing 5*1010 CFU/ mL of ATCC43504 strains of H. pylori for 3 consecutive days, twice daily via polyethylene gavage tubes. At the end of 4th week, infection with H. pylori was confirmed with stool Ag (ELISA) and following sacrifice of one mouse from each group, histopathologic study confirmed gastritis. The groups were subjected to different therapies as stated, 1: without Bismuth (Bi), Omeprazole (Om) and L. rhamnosus prescription, 2: Bi, Om and Clarithromycin (Cl) and 3: Bi, Om plus 1cc of suspension of 109 CFU/mL of L. rhamnosus. After 2 weeks, the stool was analyzed for Ag and the mice were sacrificed for evaluation of histopathologic changes. RESULTS: Treatment with L. rhamnosus group provided Zero titer of stool Ag and was associated with improved gastric inflammation in all subjects, similar to the clarithromycin group. CONCLUSION: Honey-derived L. rhamnosus probiotics provides similar results as clarithromycin in terms of improvement of H. pylori infection and gastritis in C57BL/6 Mice model, without its cons of antibiotic resistance.

RESUMO CONTEXTO: O Helicobacter pylori (H. pylori) foi reconhecido em 1983 por Marechal e Warren como protagonista principal na fisiopatologia de gastrite e úlceras gástricas. Quase metade da população mundial está infectada por H. pylori. O regime terapêutico atual contra H. pylori inclui o uso de um inibidor da bomba de prótons associada a dois ou mais antibióticos. No entanto, a eficácia deste regime está diminuindo principalmente devido à resistência aos antibióticos e efeitos colaterais de medicamentos. Este fato resultou no interesse público em outras opções terapêuticas e o papel dos probióticos merece atenção especial a este respeito. OBJETIVO: Este estudo visa avaliar a eficácia do mel-derivado do Lactobacillus rhamnosus na inflamação gástrica e infecção gastrointestinal H. pylori-induzida em camundongos C57Bl/6. MÉTODOS: Vinte e quatro camundongos C57Bl/6 foram divididos aleatoriamente em três grupos de oito camundongos cada. Todos os ratos foram alimentados com suspensão de 1cc contendo 5*1010 UFC/mL de cepas ATCC43504 de H. pylori por 3 dias consecutivos, duas vezes por dia através de gavagem por tubos de polietileno. No final da 4ª semana, a infecção com H. pylori foi confirmada pelo antígeno fecal (ELISA) e após o sacrifício de um rato de cada grupo, o estudo histopatológico confirmou gastrite. Os grupos foram submetidos a diferentes terapias, como indicado, 1: sem prescrição de bismuto (BI), Omeprazol (Om) e L. rhamnosus, 2: Bi, Om e claritromicina (CL) e 3: Bi, Om mais 1cc de suspensão de 109 UFC/mL de L. rhamnosus. Após 2 semanas, as fezes foram analisadas para o antígeno e os ratos foram sacrificados para a avaliação das alterações histopatológicas. RESULTADOS: O tratamento com o grupo L. rhamnosus forneceu o título zero de antígeno e foi associado com a inflamação gástrica melhorada em todos os camundongos, similar ao grupo claritromicina. CONCLUSÃO: O probiótico mel-derivado L. rhamnosus fornece resultados semelhantes ao da claritromicina em termos de melhoria da infecção H. pylori e gastrite em C57Bl/6 camundongos modelos, sem os inconvenientes de resistência aos antibióticos.

The Mediating Role of A2A Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat.

INTRODUCTION: The 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug and a major source of substance abuse, which ultimately leads to sensations of well-being, elation and euphoria, moderate derealization/depersonalization, and cognitive disruptions, as well as intense sensory awareness. The mechanisms involved in memory impairment induced by MDMA are not completely understood. METHODS: The current study used 40 Sprague-Dawley rats, weighted 200 to 250 g. Experiments were performed in four groups, each containing 10 rats. The first group of rats was used as the control, treated with dimethyl sulfoxide (DMSO). The second group was treated with MDMA. The third group was treated with MDMA and CGS (the adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine) (CGS 21680) and the fourth group was treated with MDMA and SCH (the A2A receptor antagonist [7-(2-phenylethyl)-5-amino-2-(2-furyl-) pyrazolo-[4, 3-e]-1, 2, 4 triazolo [1,5-] pyrimidine]) (SCH 58261). The drugs in all groups were administrated intraperitoneally (i.p.) once a day for 7 days. In 5 rats of each group, following perfusion, samples were taken from hippocampi to investigate apoptosis. Accordingly, the samples were stained using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay kit, and studied by light microscopy. In other rats, fresh tissue was also removed to study the expression of bax and bcl-2 by Western blotting technique. RESULTS: It was observed that the coadministration of MDMA with CGS reduced bax expression and prevented apoptosis of hippocampal cells. The coadministration of MDMA and SCH increased bax expression, and also increased the frequency of hippocampal cell apoptosis. CONCLUSION: The results of the current study showed that administration of CGS with MDMA decreased the common side effects associated with MDMA.

Effects of adenosine A2a receptor agonist and antagonist on cerebellar nuclear factor-kB expression preceded by MDMA toxicity.

BACKGROUND: Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliated emotional response. MDMA is a potent monoaminergic neurotoxin with the potential of damage to brain neurons. The NF-kB family of proteins are ubiquitously expressed and are inducible transcription factors that regulate the expression of genes involved in disparate processes such as immunity and ingrowth, development and cell-death regulation. In this study we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. METHODS: Sixty three male Sprague-Dawley rats were injected to MDMA (10 and 20mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03mg/kg) injection. The cerebellum were then removed forcresylviolet staining, western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results showed that MDMA increased the number of cerebellar dark neurons. RESULTS: We observed that administration of CGS following MDMA, significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. CONCLUSION: These results indicated that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.

Effects of adenosine A2a receptor agonist and antagonist on hippocampal nuclear factor-kB expression preceded by MDMA toxicity.

There is an abundance of evidence showing that repeated use of 3,4-methlylenedioxymethamphetamine (MDMA; ecstasy) is associated with brain dysfunction, memory disturbance, locomotor hyperactivity, and hyperthermia. MDMA is toxic to both the serotonergic neurons and dopaminergic system. Adenosine is an endogenous purine nucleoside with a neuromodulatory function in the central nervous system. Nuclear factor kappa-B (NF-kB) plays a pivotal role in the initiation and perpetuation of an immune response by triggering the expression of major inflammatory mediators such as cytokines, chemokines, and adhesion molecules. Here, we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Male Sprague-Dawley rats were injected to MDMA (10 mg/kg) followed by intraperitoneal injection of either CGS or SCH (0.03 mg/kg each) to animals. The hippocampi were then removed for western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results show that administration of CGS following MDMA significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. Taken together, these results indicate that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.

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.