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Nowadays, researchers pay a vast deal of attention to neural tissue regeneration due to its tremendous effect on the patient's life. There are many strategies, from using conventional autologous nerve grafts to the newly developed methods for reconstructing damaged nerves. Among the various therapeutic methods, incorporating highly potent biomolecules and growth factors, the damaged nerve site would promote nerve regeneration. The aim was to examine the efficiency of a mesenchymal stem cell condition medium (MSC-CM) loaded on a 3D-polycaprolactone (PCL) scaffold as a nerve conduit in an axotomy rat model. Twenty-four mature male rats were classified into four groups: controls (the animals of this group were intact), axotomy (10 mm piece of the nerve was removed), axotomy (10-mm piece of the nerve was removed) + scaffold, and axotomy (10-mm piece of the nerve was removed) + MSC-CM-loaded scaffold. We followed up nerve motor function using a sciatic function index and electromyography activity of the gastrocnemius muscle. At 12 weeks post axotomy, sciatic nerve and dorsal root ganglion specimens and L4 and L5 spinal cord segments were separated from the rats and were analyzed by stereological, immunohistochemistry, and RT-PCR procedures. The rats of the axotomy group presented the expected gross locomotor deficit. Stereological parameters, immunohistochemistry of GFAP, and gene expression of S100, NGF, and BDNF were significantly enhanced in the CM-loaded scaffold group compared with the axotomy group. The most observed similarity was noted between the results of the control group and the CM-loaded scaffold group. Our results support the potential applicability of MSC-CM-loaded PCL nanofibrous scaffold to treat peripheral nerve injury (PNI). [ABSTRACT FROM AUTHOR]

Evidence suggests that the effect of heavy metals on neuroimmune cells lead to neurogenic inflammatory responses. In this study, immune cells [mast cells (MCs) and microglia] and pro-neuroinflammation cytokines (interleukin-1b and tumor necrosis factor-α) were assessed in the prefrontal lobe of rat brains exposed to thimerosal in different timeframes. A total of 108 neonatal Wistar rats were divided into three groups having three subgroups. The experimental groups received a single dose of thimerosal (300 μg/kg) postnatally at 7, 9, 11, and 15 days. The vehicle groups received similar injections of phosphate-buffered saline in a similar manner. The control groups received nothing. Samples of the prefrontal cortex were collected and prepared for stereological, immunohistochemical, and molecular studies at timeframes of 12 or 48 h (acute phase) and 8 days (subchronic phase) after the last injection. The average density of the microglia and MCs increased significantly in the experimental groups. This increase was more evident in the 48 h group. At 8 days after the last injection, there was a significant decrease in the density of the MCs compared to the 12 and 48 h groups. Alterations in pro-inflammatory cytokines were significant for all timeframes. This increase was more evident in the 48 h group after the last injection. There was a significant decrease in both neuroinflammatory cytokines at 8 days after the last injection. It was found that ethylmercury caused abnormal neurogenic inflammatory reactions and alterations in the neuroimmune cells that remained for a longer period in the brain than in the blood. [ABSTRACT FROM AUTHOR]

Currently, natural polymer based hydrogels has attracted great attention of orthopedic surgeons for application in bone tissue engineering. With this aim, osteoinductive capacity of Gum Tragacanth (GT) based hydrogel was compared to collagen hydrogel and tissue culture plate (TCPS). For this purpose, adipose-derived mesenchymal stem cells (AT-MSCs) was cultured on the hydrogels and TCPS and after investigating the biocompatibility of hydrogels using MTT assay, osteoinductivity of hydrogels were evaluated using pan osteogenic markers such as Alizarin red staining, alkaline phosphatase (ALP) activity, calcium content and osteo-related genes. Increasing proliferation trend of AT-MSCs on GT hydrogel demonstrated that TG has no-cytotoxicity and can even be better than the other groups i.e., highest proliferation at day 5. GT hydrogel displayed highest ALP activity and mineralization when compared to the collagen hydrogel and TCPS. Relative gene expression levels have demonstrated that highest expression of Runx2, osteonectin and osteocalcin in the cells cultured GT hydrogel but the expression of collagen type-1 remains constant in hydrogels. Above results demonstrate that GT hydrogel could be an appropriate scaffold for accelerating and supporting the adhesion, proliferation and osteogenic differentiation of stem cells which further can be used for orthopedic applications. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have suggested that the cerebellum is a primary site of motor learning. The cerebellar cortex has a particular glial architecture with large astroglial cells. In addition, more recent works have revealed that astrocytes play a more active role in neuronal activity. The aim of this study was to evaluate the number of astrocytes in the molecular layer of rat's cerebellum after spatial learning. Methods: 21 male albino wistar rats were used in this study. Reference and working memory methods of Morris Water Maze (MWM) were used. Following behavioral testing, animals were decapitated under diethyl ether anesthesia. Brains were removed and fixed for 2 weeks for histological assessment. Finally, 7 µm thick coronal slices were cut and stained with PTAH staining for showing the astrocytes. Results: Our results showed a significant difference in the number of astrocytes between the control, reference and working memory groups. On the other hand, the number of astrocytes in the working memory group was more than the other groups. There was no difference in density of astrocytes between the lateral and medial parts of the cerebellum in any group. It seems that the distribution of astrocytes in the lateral and medial parts of cerebellum is similar. Discussion: We concluded that spatial learning such as reference or working memory methods, can increase the number of astrocytes in the cerebellum and this increase is similar in the cerebellar cortex. [ABSTRACT FROM AUTHOR]

We have surveyed the motor changes in rats subjected to sciatic nerve axotomy. The rats were divided into two groups, each one consisting of ten animals, which underwent the following intervention: The first group (control): healthy rats without any injuries and experimental group: rats with injured sciatic nerve without treatment. at 12 weeks, the L4 and L5 spinal cord segments were removed. We evaluated nerve function using muscle electromyography (EMG) activity and sciatic function index (SFI) simultaneously with histological spinal cord analyses by stereological methods at 12 week. After nerve injury presented gross locomotor deficits at week 12. We also found that the volume of the anterior horn of spinal cord and total number of motor neurons were decreased after nerve axotomy (p<0.05). In conjunction, these results indicate that peripheral nerve injuries have more severe consequences on hind limb motor output. En este estudio se examinaron los cambios motores en ratas sometidas a axotomía del nervio ciático. Las ratas se dividieron en dos grupos diez animales. El primer grupo (control) eran ratas sanas sin lesiones, y el grupo experimental consistió en ratas con nervio ciático lesionado sin tratamiento. A las 12 semanas, los segmentos de la médula espinal L4 y L5 fueron removidos. Se evaluó la función nerviosa mediante electromiografía muscular (EMG) y el índice de función ciática (IFC), simultáneamente con análisis histológicos de la médula espinal mediante métodos estereológicos. A las 12 semanas de la lesión nerviosa presentó déficit locomotor grueso. Además, se observó que el volumen del asta anterior y el número total de neuronas motoras disminuyeron después de la axotomía nerviosa (P <0,05). En conjunto, estos resultados indican que las lesiones de los nervios periféricos determinan graves consecuencias de la función motora de los miembros posteriores. [ABSTRACT FROM AUTHOR]

Introduction: Periodontitis is a set of inflammatory disorders characterized by periodontal attachment loss and alveolar bone resorption. Because of deficiency in periodontitis mechanical therapy, this study was aimed to explore the molecular influence of the erbiumdoped: yttrium aluminum garnet (Er:YAG) laser and cyclosporin A (CsA) on human gingival fibroblasts (HGFs) for improvement in periodontal diseases therapy. Methods: We focused on articles that studied the proteome profiles of HGFs after treatment with laser irradiation and application of CsA. The topological features of differentially expressed proteins were analyzed using Cytoscape Version 3.4.0 followed by module selection from the protein-protein interaction (PPI) network using Cluster ONE plugin. In addition, we performed gene ontology (GO) enrichment analysis for the densely connected region and key proteins in both PPI networks. Results: Analysis of PPI network of Er:YAG laser irradiation on HGFs lead to introducing YWHAZ, VCP, HNRNPU, YWHAE, UBA52, CLTC, FUS and IGHG1 as key proteins while similar analysis revealed that ACAT1, CTSD, ALDOA, ANXA2, PRDX1, LGALS3, ARHGDI and EEF1A1 are the crucial proteins related to the effect of drug. GO enrichment analysis of hubbottleneck proteins of the 2 networks showed the different significant biological processes and cellular components. The functional enrichments of module of Er:YAG laser network are included as fatty acid transmembrane transport, cytokinesis, regulation of RNA splicing and asymmetric protein localization. There are not any significant clusters in network of HGF treated by CsA. Conclusion: The results indicate that there are 2 separate biomarker panels for the 2 treatment methods. [ABSTRACT FROM AUTHOR]

A gradual degeneration of the striatum and loss of nigral dopamine cells are characteristic of Parkinson's disease. Nowadays, combination therapy for neurodegenerative disease is considered. This study aimed to investigate the effects of melatonin and dopaminergic neurons derived from adipose tissue stem cells (ADSCs) in a rat model of Parkinson's disease. Parkinson's disease was induced in rats using neurotoxin 6-Hydroxydopamine. The treatment was performed using melatonin and dopaminergic neurons transplantation. Subsequently, behavioral tests, western blot analysis for Caspase-3 expression, GSH (Glutathione) content and stereology analysis for the volume and cell number of substantia nigra and striatum were performed. Treatment with melatonin and dopaminergic neuron transplantation increased the number of neurons in substantia nigra and striatum while the number of glial cell and the volume of substantia nigra and striatum did not show significant change between groups. Western blot analysis for caspase 3 indicated the significant differences between groups. The results also indicated the increased level of glutathione (GSH) content in treatment groups. this study showed that combination therapy with melatonin and dopaminergic neurons could greatly protect the neurons, reduce oxidative stress and improve the symptoms of PD. [ABSTRACT FROM AUTHOR]

Background: When the spinal cord is damaged, medical procedures are vital to prevent of improvement of the lesion. Because of poor regeneration ability of central nervous tissue, the most injuries are irreversible. One of encouraging interventions for treatment of spinal cord injury is Schwann cell transplantation. However, isolation of Schwann cell for clinical interventions is complicated approach with low cells yield and purity. Thus, easily accessed sources like Adipose mesenchymal stem cells have been taken notice. Therefore, this study was planned to assess the effect of adipose stromal cell-derived Schwann cell transplantation in functional recovery after lateral hemisection in adult rats. Methods: After isolation, adipose stem cells were differentiated to Schwann cells. The differentiation was verified by immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Then, we loaded the cells into collagen scaffolds with parallel aligned canals and transplanted into rats with 3 mm lesions at T9-T10 level. Motor and sensory improvement were evaluated by open field locomotor scale, narrow beam, and tail flick tests for 60 days. Subsequently, conventional histology and immunohistochemistry were performed. Results: In vitro results revealed that mesenchymal stem cells after differentiation gained Schwann cells morphology and markers. Schwann cell-grafted group had significantly higher locomotor and sensory scores in comparison with the control and scaffold without cell groups. Histological observations showed differentiated cells have the ability to improve axonal regeneration and remyelination. Conclusion: Our study proved that adipose tissue-derived Schwann cells can change the rough environment of damaged spinal cord and support axon regeneration and enhance functional recovery, and possibly be helpful for people suffering from spinal cord injuries. [ABSTRACT FROM AUTHOR]

Background: When the spinal cord is damaged, medical procedures are vital to prevent of improvement of the lesion. Because of poor regeneration ability of central nervous tissue, the most injuries are irreversible. One of encouraging interventions for treatment of spinal cord injury is Schwann cell transplantation. However, isolation of Schwann cell for clinical interventions is complicated approach with low cells yield and purity. Thus, easily accessed sources like Adipose mesenchymal stem cells have been taken notice. Therefore, this study was planned to assess the effect of adipose stromal cell-derived Schwann cell transplantation in functional recovery after lateral hemisection in adult rats. Methods: After isolation, adipose stem cells were differentiated to Schwann cells. The differentiation was verified by immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Then, we loaded the cells into collagen scaffolds with parallel aligned canals and transplanted into rats with 3 mm lesions at T9-T10 level. Motor and sensory improvement were evaluated by open field locomotor scale, narrow beam, and tail flick tests for 60 days. Subsequently, conventional histology and immunohistochemistry were performed. Results: In vitro results revealed that mesenchymal stem cells after differentiation gained Schwann cells morphology and markers. Schwann cell-grafted group had significantly higher locomotor and sensory scores in comparison with the control and scaffold without cell groups. Histological observations showed differentiated cells have the ability to improve axonal regeneration and remyelination. Conclusion: Our study proved that adipose tissue-derived Schwann cells can change the rough environment of damaged spinal cord and support axon regeneration and enhance functional recovery, and possibly be helpful for people suffering from spinal cord injuries. [ABSTRACT FROM AUTHOR]

Disorders of sex development (DSD) are a wide-ranging group of complex conditions that influence chromosomal, gonadal, and phenotypic sex. The prevalence of DSD is very low, but affected patients deserve individualized management to improve psychological, sexual, and reproductive outcomes. This review aims to clarify the fertility potential of DSD patients who can be reared as females and their chance of becoming pregnant, especially using assisted reproductive techniques (ART). Due to the effects of DSD on internal and external genital organs, these conditions result in varying degrees of fertility potential. Fertility rate depends on the phenotype and is inversely related to the severity of the disorder. Reproductive endocrinologists and infertility specialists must be considered active partners of the interdisciplinary treatment team. With current advances in ART, pregnancy is more achievable in patients who were considered infertile at first glance. Due to the complexity of the medical management in DSD patients, more studies should be conducted to conclusively suggest the best choice for improving their fertility potential. Abbreviations: AIS: Androgen Insensitivity Syndrome; AMH: Anti-Müllerian Hormone; ART: Assisted Reproductive Technology; ASRM: American Society for Reproductive Medicine; CAH: Congenital Adrenal Hyperplasia; CAIS: Complete Androgen Insensitivity Syndrome; DHT: Dihydrotestosterone; DSD: Disorders of Sexual Development; FSH: Follicle Stimulating Hormone; GD: Gonadal Dysgenesis; ICSI: Intracytoplasmic Sperm Injection; IUGR: Intrauterine Growth Restriction; IVF: In Vitro Fertilization; IVF-ET: IVF and Embryo Transfer; LH: Luteinizing Hormone; MGD: Mixed Gonadal Dysgenesis; MRI: Magnetic Resonance Imaging; MRKH: Mayer-Rokitansky-Kuster-Hauser; US: Ultrasonography; HSG: Hysterosalpingography; PAIS: Partial Androgen Insensitivity Syndrome; PGD: Preimplantation Genetic Diagnosis; POR: P450 Oxidoreductase; PROM: Premature Rupture of Membranes; TS: Turner Syndrome; 17β-HSD III: 17β-Hydroxysteroid Dehydrogenase III; 21-OHD: 21-hydroxylase deficiency; 5α-RD-2: 5α-reductase-2 [ABSTRACT FROM AUTHOR]

[Display omitted] • Transplantation of DPSCs improved motor skills and muscle activity in rat brain lesion. • Transplantation of DPSCs prevented the atrophy of the striatum. • Transplantation of DPSCs impeded gliosis and microgliosis in rats. • Transplantation of DPSC downregulated Caspase-3 in brain lesion. • Transplantation of DPSCs decreased the expression of inflammatory cytokines, TNF and IL-1β, at mRNA level. Stem cell-based therapy has recently offered a promising alternative for the remedy of neurodegenerative disorders like Huntington's disease (HD). Herein, we investigated the potential ameliorative effects of implantation of dental pulp stem cells (DPSCs) in 3-nitropropionic acid (3-NP) rat models of HD. In this regard, human DPSCs were isolated, culture-expanded and implanted in rats lesioned with 3-NP. Post-transplantation examinations revealed that DPSCs were able to survive and augment motor skills and muscle activity. Histological analysis showed DPSCs treatment hampered the shrinkage of the striatum along with the inhibition of gliosis and microgliosis in the striatum of 3-NP rat models. We also detected the downregulation of Caspase-3 and pro-inflammatory cytokines such as TNF and IL-1β upon DPSCs grafting. Overall, these findings imply that the grafting of DPSCs could repair motor-skill impairment and induce neurogenesis, probably through the secretion of neurotrophic factors and the modulation of neuroinflammatory response in HD animal models. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is accompanied by inflammation, and the anti-inflammatory agents may have anti-seizure effects. In this investigation, the effect of deep brain stimulation, as a potential therapeutic approach in epileptic patients, was investigated on seizure-induced inflammatory factors. Materials and Methods: In the present experimental study, rats were kindled by chronic administration of pentylenetetrazol (PTZ; 34 mg/Kg). The animals were divided into intact, sham, low-frequency deep brain stimulation (LFS), kindled, and kindled +LFS groups. In kindled+LFS and LFS groups, animals received four trains of intra-hippocampal low-frequency deep brain stimulation (LFS) at 20 minutes, 6, 24, and 30 hours after the last PTZ injection. Each train of LFS contained 200 pulses at 1 Hz, 200 µA, and 0.1 ms pulse width. One week after the last PTZ injection, the Y-maze test was run, and then the rats’ brains were removed, and hippocampal samples were extracted for molecular assessments. The gene expression of two pro-inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)], and glial fibrillary acidic protein (GFAP) immunoreactivity (as a biological marker of astrocytes reactivation) were evaluated. Results: Obtained results showed a significant increase in the expression of of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and GFAP at one-week post kindling seizures. The application of LFS had a long-lasting effect and restored all of the measured changes toward normal values. These effects were gone along with the LFS improving the effect on working memory in kindled animals. Conclusion: The anti-inflammatory action of LFS may have a role in its long-lasting improving effects on seizure-induced cognitive disorders. [ABSTRACT FROM AUTHOR]

According to the studies, damages to the peripheral nerve as a result of a trauma or acute compression, stretching, or burns accounts for a vast range of discomforts which strongly impressed the patient's life quality. Applying highly potent biomolecules and growth factors in the damaged nerve site would promote the probability of nerve regeneration and functional recovery. Tissue plasminogen activator (tPA) is one of the components that can contribute importantly to degenerating and regenerating the peripheral nerves following the injuries occurred and the absence of this biomolecule hinders the recoveries of the nerves. This technique would guarantee the direct accessibility of tPA for the regenerating axons. Structural, physical, and in vitro cytotoxicity evaluations were done before in vivo experiments. In this study, twenty-four mature male rats have been exploited. The rats have been classified into four groups: controls, axotomy, axotomy + scaffold, and axotomy + tPA-loaded scaffold. Four, 8, and 12 weeks post-surgical, the sciatic functional index (SFI) has been measured. After 12 weeks, the spinal cord, sciatic nerve, and dorsal root ganglion specimens have been removed and stereological procedures, immunohistochemistry, and gene expression have been used to analyze them. Stereological parameters, immunohistochemistry of GFAP, and gene expression of S100, NGF, and BDNF were significantly enhanced in tPA-loaded scaffold group compared with axotomy group. The most similarity was observed between the results of control group and tPA-loaded scaffold group. According to the results, a good regeneration of the functional nerve tissues in a short time was observed as a result of introducing tPA. [ABSTRACT FROM AUTHOR]

Highlights • Grafted Sertoli cells (SCs) exhibited a decline in apoptosis in a rat model of amyloid beta toxicity. • Implantation of SCs in rats with Aβ1-42 receiving vehicle decreased the amount of gliosis. • We found that implanted SCs can recover hippocampus dependent memory and learning. • Transplanted SCs restored long-term synaptic plasticity in lesioned rats. Abstract Alzheimer's disease (AD) is a degenerative nerve disease which adversely affects memory and learning skills. Currently, there is no disease-modifying therapeutic approach for AD. However, a growing body of literature suggests cell based therapies as a promising remedy for neurological disorders. Among the potential cell sources, testis- derived Sertoli cells (SCs) appear to be an attractive choice due to their immune-privileged capacities. Herein, we investigated the neuro-restorative/protective effects of SC transplants in a rat model of amyloid beta toxicity. To this end, GATA-4 and vimentin positive SCs were transplanted into rats with amyloid beta induced hippocampal lesions. According to our in vivo results, implanted SCs survived, exhibited reduction in both apoptosis as well as astrocytic migration. Additionally, transplantation of SCs restored hippocampus dependent memory and learning, along with the recovery of long-term synaptic plasticity. Taken together, these data indicate that SCs are a valuable source for cell-based therapies particularly aimed at AD. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate changes of both peripheral motor function and histology of spinal anterior horn in adult rats after unilateral sciatectomy. Ten adult healthy rats served as control group, while in the ten rat experimental group the right sciatic nerve was severed. We followed-up nerve motor function using a sciatic function index and electromyography activity of the gastrocnemious muscle. The rats of the experimental group presented the expected gross locomotor deficit and leg muscle atrophy. At 12 weeks post sciatectomy, L4 and L5 spinal cord segments were removed from the twenty rats and were analysed by istological stereological methods. In the axotomized animals volume of the anterior horn and its content of motor neurons decreased, while the content of astrocytes increased (p < 0.05). Thus, in adult rats, beside the obvious peripheral nerve disfuction, the sciatic nerve axotomy have severe consequences on the soma of the injured motor neurons in the spinal anterior horn. All these quantitative analyses may be usefull to quantify changes occurring in adult animals after axotomy and eventual management to modify the final outcomes in peripheral nerve disorders. [ABSTRACT FROM AUTHOR]

Spinal cord injury is a significant cause of motor dysfunctions. There is no definite cure for it, and most of the therapeutic modalities are only symptomatic treatment. In this systematic review and meta-analysis, the effectiveness of stem cell therapy in the treatment of the spinal cord injuries in animal models was studied and evaluated. A systematic search through medical databases by using appropriate keywords was conducted. The relevant reports were reviewed in order to find out cases in which inclusion and exclusion criteria had been fulfilled. Finally, 89 articles have been considered, from which 28 had sufficient data for performing statistical analyses. The findings showed a significant improvement in motor functions after cell therapy. The outcome was strongly related to the number of transplanted cells, site of injury, chronicity of the injury, type of the damage, and the induction of immune-suppression. According to our data, improvements in functional recovery after stem cell therapy in the treatment of spinal cord injury in animal models was noticeable, but its outcome is strongly related to the site of injury, number of transplanted cells, and type of transplanted cells. [ABSTRACT FROM AUTHOR]

Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD. To this end, UCMSCs were isolated, immunophenotypically characterized by the positive expression of MSC markers, and exhibited multilineage potentiality. Besides, synthesis of neurotrophic factors of GDNF and VEGF by UCMSC was confirmed. Initially, PC12 cells were exposed to superoxide in the presence of conditioned media (CM) collected from UCMSC (UCMSC-CM) and cell viability plus neuritogenesis were measured. Next, bilateral striatal transplantation of UCMSC in 3-nitropropionic acid (3-NP) lesioned rat models was conducted, and 1 month later, post-graft analysis was performed. According to our in vitro results, CM of UCMSC protected PC12 cells against oxidative stress and considerably enhanced cell viability and neurite outgrowth. On the other hand, transplanted UCMSC survived, decreased gliosis, and ameliorated motor coordination and muscle activity, along with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. Collectively, our findings imply that UCMSCs provide an enriched platform by largely their paracrine factors, which downgrades the unfavorable effects of oxidative stress. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that differentiation of stem cells into cardiomyocytes is a complex phenomenon that requires sufficient inducing factors at various time points. Cardiac extracellular matrix (cECM) could provide tissue specific microenvironment and act as an inductive template for efficient cell differentiation. The aim of this study was to investigate the effect of cECM on differentiation of human adipose tissue-derived stem cells (hADSCs) into cardiomyocytes using cECM hydrogel in combination with a cardiac inductive cocktail. hADSCs were cultured on ECM-coated plates with and without inductive cocktail for 3weeks. qRT-PCR and western blot analysis were used to evaluate the expression pattern of special cardiac genes and proteins. When hADSCs were cultured in the presence of cECM cardiac genes including GATA4, HAND1, HAND2, NKX2.5, Troponin I, βMHC, Connexin43 were highly expressed in differentiated cells. Also Connexin43, cTnI and βMHC proteins were expressed as well. We could show that cECM by itself could affect viability, proliferation and differentiation of hADSCs. However, combination of cECM with a cardiac inducing cocktail could improve the results. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a richest plant-based source of antioxidants. In this study, the effects of flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression and protein content of neurotrophic factors in motor cortex area in rat model of brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group) were randomly divided into four groups of Control (Co+normal saline [NS]), Sham (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of reperfusion, neurological examination was performed, and animals were sacrificed, and their brains were used for molecular and histopathological studies. FSO significantly improved the functional motor recovery compared with tMCAo+NS group (P<0.05). A significant reduction in brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) mRNAs and protein levels were observed in the tMCAo+NS group compared with Co+NS and Sh+NS group (P<0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in the tMCAo+FSO group compared with Co+NS, Sh+NS and tMCAO+NS groups (P<0.05). The results of the current study demonstrated that pretreatment with FSO had neuroprotective effects on motor cortex area following cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF). [ABSTRACT FROM AUTHOR]

The square subgroup of an abelian group which is denoted by , can be understood as a subgroup of A generated by the squares of all possible rings defined on A. Clearly, this generalizes the classical concept of a nil group. In this paper, the square subgroups of some decomposable torsion-free abelian groups are studied. In particular, we obtain new results about the square subgroups of some decomposable torsion-free abelian groups of rank three. [ABSTRACT FROM AUTHOR]

Background: Apical surfaces of human endometrial epithelium and endothelium are key elements for the initiation of molecular interactions to capture the blastocyst or leukocyte, respectively. The L-selectin adhesion system has been strongly proposed to play an important role in the initial steps of trophoblast adhesion and promotion of integrin-dependent processes, ultimately culminating in the establishment of the embryo-maternal interface. On the basis of these facts, we hypothesized a novel role for pinopodes as the first embryo-fetal contact sites to contain the highest subcellular expression of L-selectin ligand suggesting its role in early adhesion as predicted. Thus, the objective of this study was therefore to determine the subcellular pattern of distribution of the L-selectin ligand (MECA-79) in human endometrial apical membrane region during the window of implantation. Methods: Endometrial biopsies of secretory phases from fertile females ranging in age between 25 and 42years were studied using several approaches, including scanning electron microscopy (SEM), immunostaining for light microscopy and transmission electron microscopy (TEM), and immunoblotting as well as statistical analysis of the area-related numerical densities of immunoreactive MECA-79-bound nanogolds to detect the expression pattern and the subcellular distribution pattern of L-selectin ligand (MECA-79) in human endometrium during the window of implantation. Results: The endometrial biopsies were scored according the dating criteria of Noyes et al. by an experienced histologist. The SEM images of the midluteal phase specimens revealed that fully developed pinopodes were abundant in our samples. HRP-immunostaining and immunofluorescent staining as well as immunoblotting revealed that MECA-79 was expressed in the midluteal phase specimens. The results of immunogold TEM illustrated the expression of MECA-79 in human pinopodes in the midluteal phase and a higher area-relate numerical density in pinopodes compared to that of the uterodome-free areas. Conclusions: This is the first demonstration of the subcellular localization of MECA-79 in the human pinopodes which may indicate a novel role for pinopodes to be capable of shear-stress-dependent tethering-type adhesion in the initial phases of human embryo implantation. [ABSTRACT FROM AUTHOR]

Background: Apical surfaces of human endometrial epithelium and endothelium are key elements for the initiation of molecular interactions to capture the blastocyst or leukocyte, respectively. The L-selectin adhesion system has been strongly proposed to play an important role in the initial steps of trophoblast adhesion and promotion of integrin-dependent processes, ultimately culminating in the establishment of the embryo-maternal interface. On the basis of these facts, we hypothesized a novel role for pinopodes as the first embryo-fetal contact sites to contain the highest subcellular expression of L-selectin ligand suggesting its role in early adhesion as predicted. Thus, the objective of this study was therefore to determine the subcellular pattern of distribution of the L-selectin ligand (MECA-79) in human endometrial apical membrane region during the window of implantation. Methods: Endometrial biopsies of secretory phases from fertile females ranging in age between 25 and 42 years were studied using several approaches, including scanning electron microscopy (SEM), immunostaining for light microscopy and transmission electron microscopy (TEM), and immunoblotting as well as statistical analysis of the area-related numerical densities of immunoreactive MECA-79-bound nanogolds to detect the expression pattern and the subcellular distribution pattern of L-selectin ligand (MECA-79) in human endometrium during the window of implantation. Results: The endometrial biopsies were scored according the dating criteria of Noyes et al. by an experienced histologist. The SEM images of the midluteal phase specimens revealed that fully developed pinopodes were abundant in our samples. HRP-immunostaining and immunofluorescent staining as well as immunoblotting revealed that MECA-79 was expressed in the midluteal phase specimens. The results of immunogold TEM illustrated the expression of MECA-79 in human pinopodes in the midluteal phase and a higher area-relate numerical density in pinopodes compared to that of the uterodome-free areas. Conclusions: This is the first demonstration of the subcellular localization of MECA-79 in the human pinopodes which may indicate a novel role for pinopodes to be capable of shear-stress-dependent tethering-type adhesion in the initial phases of human embryo implantation. [ABSTRACT FROM AUTHOR]

Background: Skin-derived precursors (SKPs) are a type of progenitor cells extracted from mammalian dermal tissue and can be differentiate to neural and mesodermal lineage in vitro. These cells can introduce an accessible autologos source of neural precursor cells for treatment of different neurodegenerative diseases. This research was done in order to set up isolation, culture, proliferation and differentiation of human skin derived precursors (hSKPs). Methods: Human foreskin samples were cut into smaller pieces and cultured in proliferation medium after enzymatic digestion. To induce neural differentiation, cells were cultured in neural differentiation medium after fifth passage. We used immunocytochemistry and RT-PCR for characterization of the cells. Neuron and glial cell differentiation potential was assessed by immunofloresence using specific antibodies. The experiments were carried out in triplicate. Results: After differentiation, βIII- tubulin and neurofilament-M positive cells were observed that are specific markers for neurons. Moreover, glial fibrillary acid protein (GFAP) and S100 positive cells were identified that are markers specifically express in glial cells. Detected neurons and glials were also confirmed by their morphologic characterizations. Conclusion: Our results demonstrated that skin-derived precursors obtained from human foreskin can exhibit neuronal and glial differentiation potential in vitro, depending on the protocols of induction. [ABSTRACT FROM AUTHOR]

Abstract: The hippocampus is essentially involved in learning and memory, and is known to be a target for androgen actions. As neuron–astrocyte interactions play a crucial role during development and in the adult brain, it is thought that astrocytes support learning and memory through specific mechanisms. In this study, the effect of testosterone-induced impairment of acquisition and retrieval of long-term memory, on the number of astrocytes was studied. Adult male albino Wistar rats were bilaterally cannulated into the CA1 region and received 80μg/0.5μl of testosterone enanthate dissolved in DMSO as vehicle. In trained groups injection was done 30min before training. Our results showed that pre-training administration of testosterone increased escape latency and the traveled distance, as compared to intact or DMSO administered (sham-operated) counterparts. Testosterone administration also increased the number of astrocytes in rats, compared to sham-operated and intact animals in both trained and non-trained groups. We have also found that spatial learning could increase the number of astrocytes in the hippocampus as a center of long-term learning and memory and recall. It is concluded that, testosterone-induced impairment in learning and memory, causes an increase in the number of astrocytes in the CA1 region of rat hippocampus. [Copyright &y& Elsevier]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

• THC administration interrupts long term memory and long term potentiation. • Stereological studies revealed considerable atrophy in hippocampus. • Several signaling cascades related to synaptic regulation were interrupted in hippocampus under THC administration. Tetrahydrocannabinol (THC), a major psychoactive constituent of marijuana, can substantially change the function of several brain areas, leading to behavioral impairment including memory and learning dysfunction. Given the importance of hippocampus as one of the chief parts of the brain involved in memory processing, the present study seeks to investigate structural and histological alterations in hippocampus as well as behavioral defects provoked by THC treatment. Besides, using genome-wide sequencing, we adopted a pathway-based approach to discover dysregulated molecular pathways. Our results demonstrated remarkable hippocampal atrophy, and also interrupted memory function and long term potentiation (LTP) under THC exposure. We also detected several dysregulated signaling pathways involved in synaptic plasticity as well as cell-cell interaction in the hippocampus of THC-treated rats. Overall, the results indicate a potential correlation between disrupted signaling cascades, hippocampal atrophy and memory defects caused by THC treatment. [ABSTRACT FROM AUTHOR]

Recent evidences showed that, noise stress causes abnormal changes in structure and function of central nervous system (CNS). The Current study was conducted to evaluate some stereological parameters of the medial prefrontal cortex (mPFC) of male pups of Wistar rat after prenatal and early postnatal noise stress. 18 pregnant Wistar rats were randomly divided into prenatal noise-exposed (NE) group, postnatal NE group, and controls. Male pups of NE groups were exposed to noise 100 dB at the frequency ranges of 500–8000 Hz, 4 h per day from gestational day one (GD1) to GD21 for the prenatal NE group, and from postnatal day one (PND1) to PND21 in the postnatal NE group. The Control group animals were maintained under standard condition without noise stimulation. Corticosterone level in plasma was measured using ELISA technique. Changes of the neurons and non-neurons cells number and volume of the mPFC were evaluated by stereological analysis. Tunnel assay was also used for detection of apoptotic cells. Increase in plasma corticosterone level, decrease in the number of neurons, and increase in the apoptotic cells number were observed in both NE groups. Decrease in volume of mPFC and also in non-neurons cells number was observed in the prenatal NE group. An increase in the non-neurons number was seen in the postnatal NE group. Data of the current comparative study showed that, noise stress during prenatal and early postnatal periods can induce the abnormal alteration in some stereological parameters of mPFC in male pups of Wistar rat. These negative alterations were more remarkable after prenatal noise stress. [ABSTRACT FROM AUTHOR]

•.Alpha Lipoic Acid has a protective effect on brain cells. • THIM has a toxic effect on the developing brain. • Alpha Lipoic Acid decreaces the glutathione content of prefrontal cortex. • ALA is one of the important antioxidants that can prevent the adverse effects of THIM-containing products. Thimerosal (THIM) is a common preservative used in many pharmaceutical drugs, vaccines, cosmetics and many other products. Today, it was somewhat clear that Thimerosal (THIM) is a neurotoxicant preservative. We aimed to use of a suitable agent for preventing of THIM side effects on brain. Therefore, in this research, the protective effects of Alpha Lipoic Acid (ALA), against THIM-induced brain cell loss, changes in neuroimmune cell and enzymatically contents were examined. Male Wistar rats (n = 60) were randomly distributed into five groups: 1- THIM group; this group received THIM at dose of 300 μg /kg on 7, 9, 11, 15 days after birth 2- ALA group; received ALA (20 mg/kg) in the same order. 3- THIM & ALA group; this group received ALA in the same dose, 30 min before THIM administration.4& 5; Saline and ALA vehicle groups were also included. At 56th postnatal day, samples of the prefrontal cortex were collected and prepared for stereological, immune-histochemical, and enzymatic evaluations. The result showed that ALA, prevents the adverse effects of THIM on brain cell loss, abnormal changes in neuroimmune cells (p < 0.05), prefrontal cortex volume (p < 0.05), and the glutathione content of prefrontal cortex (p < 0.05). In conclusion, neonatal exposure to THIM can induce abnormal alterations in neuroimmune cells and brain cell density as well as prefrontal cortex volume & glutathione content, and ALA can ameliorate these abnormalities. [ABSTRACT FROM AUTHOR]

Melatonin is primarily secreted by the pineal gland in dark. In addition to its role as an internal sleep facilitator, melatonin acts as an antioxidant, anti-inflammatory and neuroprotective agents. melatonin has been introduced as a therapeutic strategy for sleep disorders. Hence, in the present study, we studied the neuroprotective effects of pre- and post-treatment of melatonin in locus coeruleus nucleus (LC) of rapid eye movement (REM) sleep deprived (REM-SD) male adult rats. Adult male rats of control, sham and trial groups were used Exogenous melatonin (ExMe) was intraperitoneally injected in two forms of pre and post treatment. The protein level of cleaved caspase-3, the number and density of tyrosine hydroxylase (TH) positive neurons and the microglia population in LC were studied by western blot and immunohistochemistry respectively. Morphological changes of LC nucleus and its neurons were also studied by using stereological analysis. The number of neurons and volume of LC was reserved in animals that had received post-RSD ExMe. Apoptosis significantly was decreased comparing to RSD and Pre-RSD animals. Melatonin post-treatment of RSD rats also decreased cleavage of caspase-3 and increased reduced glutathione content in LC. Moreover, immunohistochemistry analysis showed an increase in the number of TH positive neurons and a decrease in microglia migration. Based on our findings antioxidant properties of exogenous melatonin could play a critical role in certain types of sleep disorders. [ABSTRACT FROM AUTHOR]