ObjectiveTo determine the radioprotective effects of Silymarin in adult male Sprague-Dawley rats irradiated with γ-rays.MethodsThe present experimental study was performed in Tehran University of Medical Sciences, Tehran, Iran from December 2009 to March 2010. The study was performed on 40 rats, which were randomly and equally divided into four groups: 1) control group: neither received Silymarin nor irradiated with γ-rays; 2) γ-irradiation group: testis region exposed to 2Gy of γ-rays; 3) Silymarin & γ-irradiation: rats received 100 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays; 4) Silymarin & γ-irradiation: rats received 200 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays. After animal experiments and preparing the tissue sections, different histological and histomorphological parameters of seminiferous tubules and the biological characteristics of Leydig cells were evaluated applying quantitative assessment, Johnson scoring, and Leydig cell apoptosis assay by TUNEL method. The data were analyzed applying ANOVA and Tukey’s post hoc test, using SPSS software (V.19).ResultsIrradiation of 2 Gy γ-rays to the testis of the rats significantly affected the frequency of spermatogonia, primary spermatocyte, round spermatid, spermatozoa, seminiferous tube and lumen diameters, thickness of the epithelium, Leydig cell nuclear diameter and volume, epithelium height, and apoptotic cells (p<0.05). However, administration of Silymarin improved the mentioned parameters specifically in 200 mg/kg of dosage.ConclusionSilymarin could act as a potent radioprotector and it can be used in modulation as well as improvement to radiation therapy to prevent male reproductive function, specifically seminiferous tubules in an animal model; however, its molecular mechanism is still not clear and needs more molecular researches.

Background:Bone marrow mesenchymal stem cells (BM-MSCs) elicit neuroprotective effects, and their repair ability has been investigated in different experimental models. We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice.Methods:Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for six weeks. Bone marrow samples were taken from patients with spinal cord injury. BM-MSCs (2 × 106 in 1 milliliter medium) were administered intraperitoneally for two consecutive weeks at the end of the forth weeks of cuprizone administration. Animals (n = 12) were perfused with 10% paraformaldehyde at the end of sixth week. The brains were sectioned coronally in 6-8-μm thickness (-2.3 to 1.8 mm from bregma). The sections were stained by luxol fast blue-cresyl violet, and images were captured via a microscope. Demyelination ratio was estimated in corpus callosum in a blind manner. A quantitative real-time PCR was used to measure the myelin basic protein gene expression at sixth week.Results:Histologically, cuprizone induced demyelination in the corpus callosum. Demyelinated area was diminished in the corpus callosum of cell-administered group. Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM-MSCs injections.Conclusion:Our data indicated a remyelination potency of multiple i.p. BM-MSCs in the cuprizone model of multiple sclerosis in mice.

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon- gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months’(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood.

Background: Many recent epidemiological studies have shown that epileptic patients are more likely suffer from depression, anxiety, and irritability. However, the cellular mechanisms of epilepsy-induced psychotic behaviors are not fully elucidated. Neurotrophin receptors have been suggested to be involved in epilepsy and also in psychiatric disorders. Up-regulation of p75NTR expression and activation of p75NTR signalling cascades after the seizure have been shown, but the role of the p75 receptor in epilepsy-induced psychotic behaviors has not been documented so far. Therefore, the present work aimed to investigate the effect of p75 receptor blockade on seizure activity, irritability, and anxiety-like behaviors in a rat model of status epilepticus. Methods: Rats were injected with pilocarpine (350 mg/ kg, i.p.) to induce status epilepticus. Then various behavioral tests were performed after the blockade of p75NTR alone or in combination with p75 antagonist and phenobarbital. Molecular analysis by PCR was performed to investigate the expression of p75 and pro-NGF. Results: Molecular findings indicated a high level of mRNA expression for both p75 receptors and pro-NGF in the epileptic model group. Results also showed that the administration of p75 antagonist alone or in combination with phenobarbital was able to significantly influence the behavioral responses. Furthermore, 20-hours video monitoring showed a decrease in the frequency and duration of seizures in the rat group receiving p75 antagonist. Conclusion: Taken together, the present study suggests that the blockade of the p75 receptor may affect the irritability and anxietyrelated behavior in a rat model of status epilepticus.

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