Changes in the Hypothalamic-Pituitary-Gonadal Axis in Adult Male Rats Poisoned with Proteus and Biscaya Insecticides.

BACKGROUND: Insecticides may have negative effects on reproductive organs. Given the interaction between leptin and the hypothalamic-pituitary-gonadal (HPG) axis, we sought to investigate the changes in leptin and the HPG axis in adult male rats poisoned with Proteus and Biscaya insecticides. METHODS: Our experimental subjects were 110 adult male Wistar rats (80-90 days of age; average weight=200-210 g). They were randomly split into 11 groups of 10 rats: control, sham, and 9 experimental groups namely treatment with 2.75, 5.5, and 11 mg/kg/BW of Proteus, treatment with 1.5, 3, and 6 mg/kg/BW of Biscaya, treatment with 2.75 mg/kg/BW of Proteus+1.5 mg/kg/BW of Biscaya, treatment with 5.5 mg/kg/BW of Proteus+3 mg/kg/BW of Biscaya, and treatment with 11 mg/kg/BW of Proteus+6 mg/kg/BW of Biscaya. Intraperitoneal injections were performed over a 14-day period. For bloodletting at the end of the experiment, blood samples were withdrawn from the rats in order to investigate the serum concentration of luteinizing hormone (LH), follicle-stimulating hormone (FSH), gonadotropin- releasing hormone (GnRH), testosterone, and leptin. The data were analyzed using SPSS, version 16, via ANOVA and the Duncan test. A P value equal to or less than 0.05 was considered statistically significant. RESULTS: Our comparisons between the experimental groups (average and maximum compound concentrations of Proteus and Biscaya) and the control group showed a significant decrease in the mean serum levels of FSH (P=0.001), LH (P=0.001), GnRH (P=0.001), testosterone (P=0.005), and leptin (P=0.001) in all the experimental groups in a dose-dependent manner. CONCLUSION: Proteus and Biscaya decreased GnRH, LH, FSH, and testosterone by reducing the serum level of leptin in the hypothalamus in a dose-dependent manner.

Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in Mice.

Spinal cord injury (SCI) is a drastic disability that leads to spinal cord impairment. This study sought to determine the effects of bone marrow stem cells (BMSCs) on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly divided into 3 groups: control (2 subcategories), subjected to no intervention; sham (3 subcategories), subjected to acute SCI; and experimental (2 subcategories), subjected to SCI and cell transplantation. In the experimental group, 2×105 BMSCs were injected intravenously 1 day after SCI. The mesenchymal property of the cells was assessed. The animals in the 3 groups were sacrificed 1, 21, and 35 days after the induction of injury and caspase-3 levels were evaluated using a caspase-3 assay kit. The obtained values were analyzed with ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the transplanted cells were spindle-shaped and were negative for the hematopoietic markers of CD34 and CD45 and positive for the expression of the mesenchymal marker of CD90 and osteogenic induction. The caspase-3 levels showed a significant increase in the sham and experimental groups in comparison to the control group. One day after SCI, the caspase-3 level was significantly higher in the sham group (1.157±0.117) than in the other groups (P<0.000). Twenty-one days after SCI, the caspase-3 level was significantly lower in the experimental group than in the sham group (0.4±0.095 vs. 0.793±0.076; P˂0.000). Thirty-five days following SCI, the caspase-3 level was lower in the experimental group than in the sham group (0.223±0.027 vs. 0.643±0.058; P˂0.000). We conclude that BMSC transplantation was able to downregulate the caspase-3 level after acute SCI, underscoring the role of caspase-3 as a marker for the assessment of treatment efficacy in acute SCI.

Exosome Therapy and Photobiomodulation Therapy Regulate mi-RNA 21, 155 Expressions, Nucleus Acetylation and Glutathione in a Polycystic Ovary Oocyte: An In Vitro Study.

Introduction: Polycystic ovary syndrome (PCOS) is a complex condition that can have various symptoms and complications, one of which is infertility. Dysregulation of miRNA has been associated with the pathogenesis of numerous illnesses such as PCOS. In this study, we evaluated the effect of photobiomodulation therapy (PBMT) and exosome therapy (EXO) on the regulation of miRNA and nucleus acetylation in a PCOS oocyte. Methods: In this research, 36 oocytes divided into three groups: control, EXO, and PBM (Wavelength of 640 nm). Subsequently, in-vitro maturation (IVM) was evaluated. Real-time PCR was used to evaluate miRNA-21,16,19,24,30,106,155 and GAPDH. Afterward, oocyte glutathione (GSH) and nucleus acetylation were measured by H4K12. Results: The expression of the miR-16, miRNA-19, miRNA-24, miRNA-106 and miRNA-155 genes in the EXO and PBMT groups was significantly down-regulated in comparison to the control group, but the expression of miRNA-21 and miR-30 significantly increased in the EXO and PBMT groups in comparison to the control group. The EXO and PBMT significantly increased GSH and nucleus acetylation (P<0.0001). Conclusion: The results of this study showed that the use of EXO and PBMT can improve GSH and nucleus acetylation in the PCOS oocyte and also change the expression of miRNAs.

Evidence for crossing the blood barrier of adult rat brain by human adipose-derived mesenchymal stromal cells during a 6-month period of post-transplantation.

BACKGROUND AIMS: Therapeutic promises of adult stem cells have been overshadowed by an elicited immune response, low maintenance of implanted cells or concerns regarding their migration to non-target sites. These problems might be lessened by the use of immune privilege cells and tissues for implantation. METHODS: In this study, human adipose-derived mesenchymal stromal cells (hADMSCs) were stably transfected with a vector containing Turbo green fluorescent protein (GFP) and JRed, which allows tracing the cells after transplantation. Labeled hADMSCs were transplanted into the adult rat brain followed by assessment of their survival and migration during 6 months after transplantation. RESULTS: Results indicate that there were no postsurgical complications, and the animals thrived after transplantation. The lesions of the surgical process were remarkable at the first weeks, and a high number of transplanted cells were accumulated around them. Cell populations declined over time as they partly migrated away from the injection sites; nonetheless, they were detectable at each examination time point. Although the cells could survive and remain at the injection site for up to 6 months, some of them drifted to spleen, which is an indication of their ability to cross the blood-brain barrier. CONCLUSIONS: Despite the high survival rate of hADMSCs in the xenogenic condition, which is an ideal criterion in cell therapy, irregular migration tendency must be handled with caution.

Computational screening of FDA-approved drugs to identify potential aromatase receptor inhibitors for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of infertility without ovulation. Aromatase inhibitors were first proposed as new ovulation-inducing drugs in anovulatory women with an inadequate response to clomiphene. Letrozole is an aromatase inhibitor used as an ovulation inducer in infertile women due to PCOS. However, there is no definitive treatment for women with PCOS and the treatments are mostly symptomatic. In this study, we intend to introduce alternative drugs to letrozole using the library of FDA-approved drugs and evaluate the interaction of these drugs with the aromatase receptor. For this aim, molecular docking was performed to identify interactions of FDA-approved drugs with essential residues in the active site of the aromatase receptor. 1614 FDA-approved drugs were docked with aromatase receptor using AutoDock Vina. Molecular dynamics (MD) simulation study was also performed for 100 ns to verify the stability of the drug-receptor complexes. MMPBSA analysis evaluate the binding energy of selected complexes. Finally, acetaminophen, alendronate, ascorbic acid, aspirin, glutamine, hydralazine, mesalazine and pseudoephedrine drugs showed the best results in interaction with aromatase receptor based on computational studies. These drugs can be introduced as an alternative to letrozole for treating PCOS.Communicated by Ramaswamy H. Sarma.

Extracellular Vesicle-Derived Cord Blood Plasma and Photobiomodulation Therapy Down-Regulated Caspase 3, LC3 and Beclin 1 Markers in the PCOS Oocyte: An In Vitro Study.

Introduction: Polycystic ovary syndrome (PCOS) is the communal endocrine illness in women and the most common cause of infertility due to lack of ovulation. The exact cause of PCOS is still unknown. Affected women may have difficulty getting pregnant due to ovulation problems. Various methods have not been effective in the treatment of PCOS due to the positive role of photobiomodulation therapy (PBMT) and extracellular vesicles (ECV) obtained from cord blood plasma in the treatment of various diseases. The aim of this study was to study the role of ECV and PBMT in maturation and improvement of infertility in women with PCOS. Methods: In this research, a number of oocytes were obtained after ovarian stimulation from women who had been referred to the hospital for infertility treatment after obtaining personal consent, and they were divided into three groups: control, ECV and PBMT. Subsequently, in vitro maturation (IVM) was assessed, then some oocytes were cultured with a routine medium and others were treated with ECV and PBMT. Real-time PCR was used to evaluate BCL-2, BAX, caspase-3, and autophagy gene (ATG5, LC3, Beclin 1). Oocyte glutathione (GSH), oxidised gluathione (GSSG), and reactive oxygen species (ROS) were measured. Results: The metaphase II (MII) oocyte ratio formation significantly increased in the ECV and PBMT groups (P<0.05). The expression of the BCL-2 gene was significantly up-regulated in the ECV and PBMT groups, but the expression of BAX and caspase-3 significantly decreased (P<0.05). The expression of the ATG5, LC3, BECLIN-2 genes significantly decreased in the ECV and PBMT groups (P<0.05). ROS, GSSG decreased in ECV and PBMT groups but GSH increased (P<0.05). Conclusion: The use of ECV and PBMT can increase the rate of fertilization and maturation of an oocyte and cause a decrease in apoptosis, autophagy, and ROS in a PCOS oocyte.

The Effects of Hesperidin on BDNF/TrkB Signaling Pathway and Oxidative Stress Parameters in the Cerebral Cortex of the Utero-placental Insufficiency Fetal Rat Model.

INTRODUCTION: Uteroplacental Insufficiency (UPI) produces critical neurodevelopmental problems affecting the Intrauterine Growth Restricted (IUGR) in offspring. This study aimed to investigate the possible neuroprotective roles of Hesperidin (Hes) on the fetal cerebral cortex of the UPI rat model. METHODS: In this experimental study, 40 pregnant Wistar rats (age: ∼40 days, Mean±SD weight: 180±10 g) were randomly divided into 5 groups (n= 8/group). The study groups included control (normal saline, orally), UPI+NS (uterine vessel ligation+normal saline, orally), UPI+HES25, UPI+HES50, and UPI+HES100 (uterine vessel ligation+25, 50 and 100 mg/kg Hes, orally). After being anesthetized by ketamine and xylazine, UPI was induced by permanent bilateral closure of the uterine vessels on Gestation Day (GD) 18. From GD15, the Hes/NS-treated groups received Hes/normal saline until GD21. On GD21, the uterus, placenta, and fetus were dissected out and weighed. The oxidative stress parameters, including Catalase (CAT) activity, Malondialdehyde (MDA), and Total Antioxidant Capacity (TAC) were measured in the fetal cerebral cortex. The expression of Brain-Derived Neurotrophic Factor (BDNF) and Tropomyosin Receptor Kinase B (TrkB) was assessed by RT qPCR methods. The obtained data were analyzed by Analysis of Variance (ANOVA) and Tukey's post hoc test. RESULTS: The present study findings identified a significant difference in the uterine and fetus weight in Hes-treated mothers (P< 0.05). In the fetus, Hes reduced MDA, and increased CAT activity and TAC (P<0.001 in the UPI+Hes100 group, compared to the UPI+NS group). UPI reduced BDNF and TrkB mRNA expression, compared to the control group (P<0.05). Also, Significant increases in BDNF and TrkB mRNA expression were observed after administrating Hes in the fetal cerebral cortex of the UPI rat model, in a dose-dependent manner (P<0.05). CONCLUSION: Hes, as a neuroprotective and antioxidant agent, accelerates BDNF-TrkB signaling pathway and suppresses oxidative stress parameters in the cerebral cortex of the UPI rat model.

Age Associated Changes in Transcription of Adiponectin, AdipoR1 and AdipoR2 Genes in Pancreas of Rats.

OBJECTIVE: Adiponectin has a crucial role in the function, proliferation and viability of ß-cell via action of two receptors: AdipoR1 and AdipoR2. Nevertheless, age related change of Adiponectin system genes in pancreas is unclear or controversial. This study sought to investigate the effects of aging process on serum Adiponectin levels, Adiponectin and its receptor expression in the rat pancreas. MATERIALS AND METHODS: In this experimental study, insulin resistance markers including serum insulin and glucose concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), glucose induced insulin secretion (GIIS), serum Adiponectin levels, pancreatic expression of Adiponectin and its receptors were studied in male Sprague-Dawley rats at the age of 2, 5, 10, 18, 52 and 72 weeks of age. RESULTS: We found that aging triggered signs of insulin resistance characteristics in rats at 72 age weeks including marked insulin reduction, hyperglycemia and increased HOMA-IR. Circulating Adiponectin as well as pancreatic expression of Adiponectin and AdipoR1 was gradually decreased with age, while the opposite expression pattern of AdipoR2 was observed in the old rats. CONCLUSION: Because Adiponectin and Adiponectin signaling have crucial role in ß-cell function and viability, we concluded that reduction of Adiponectin signaling may be involved in aging induced ß-cell dysfunction. As a result, manipulation of Adiponectin signaling may be a beneficial approach for improvement of ß-cell function in the old people.

Antioxidant therapies in attention deficit hyperactivity disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder among children and adults. Impulsivity, inattention, and hyperactivity are hallmark of ADHD. While ADHD is not on the autism spectrum, they are related in several ways as they have some overlapping symptoms. The pathogenesis of ADHD has so far remained enigmatic, however, there is some evidence suggesting critical association among ADHD and the level of oxidative stress which trigger cell membrane damage, changes in inner structure and function of proteins, as well as structural damage to DNA which eventually culminate into development of ADHD. Although stimulants as well as some classes of non-stimulants are used to ameliorate symptom of ADHD, various adverse effects have been associated with such compounds. To date, treatment of ADHD is done with a combination of medications, behavior modifications, psycho-education, family therapy and life-style changes. The American Academy of Pediatrics officially promote stimulant medications and/or behavior therapy as 'first line of therapy'. In addition to the presently therapeutic armamentarium, evidences are emerging on relevancy of natural products. There has been an interest on the therapeutic role of antioxidants in the treatment of ADHD. The present review aims to highlight the beneficiary role played by different antioxidants in mitigating the symptoms of ADHD.

Intrauterine xenotransplantation of human Wharton jelly-derived mesenchymal stem cells into the liver of rabbit fetuses: A preliminary study for in vivo expression of the human liver genes.

OBJECTIVES: End-stage hepatic failure is a potentially life-threatening condition for which orthotopic liver transplantation is the only effective treatment. However, a shortage of available donor organs for transplantation each year results in the death of many patients waiting for liver transplantation. Xenotransplantation, or the transplantation of cells, tissues, or organs between different species, was proposed as a possible solution to the worldwide shortage of human organs and tissues for transplantation. The purpose of this preliminary study was to reconstruct human liver tissue by xenotransplantation of human Wharton jelly mesenchymal stem cells (hWJ-MSCs) into fetal rabbit. MATERIALS AND METHODS: Isolation and confirmation of hWJ-MSCs from human umbilical cord was performed. Eight rabbits at gestational day 14 were anesthetized. All rabbits carried pregnancies to term yielding 40 rabbit fetuses. Intrauterine injection of hWJ-MSCs was performed in 24 fetuses. Twenty-seven fetuses were born alive. Ten liver samples from injected fetuses were sampled, eight rabbits 3 days after birth and two rabbits 21 days after birth. The non-injected fetuses served as positive control. Fetuses of non-injected rabbits were negative controls. Using real-time polymerase chain reaction (RT-PCR), mRNA expression of albumin (ALB), α-fetoprotein (AFP), hepatic nuclear factor 4 (HNF4), and CYP2B6 (CYP) were detected in liver samples. RESULTS: The human ALB, AFP, HNF4, and CYP mRNAs were expressed in the injected sampled fetuses by hWJ-MSCs into fetuses of rabbits in utero. CONCLUSION: Developing xenotransplantation of hWJ-MSCs into rabbit uterus can introduce an applied approach for producing human liver tissue in rabbits.

Histopathological Analysis from Gallic Acid Administration on Hippocampal Cell Density, Depression, and Anxiety Related Behaviors in A Trimethyltin Intoxication Model.

OBJECTIVE: The present study investigated the effects of gallic acid (GA) administration on trimethyltin chloride (TMT) induced anxiety, depression, and hippocampal neurodegen- eration in rats. MATERIALS AND METHODS: In this experimental study, the rats received intraperitoneal (i.p.) injections of TMT (8 mg/kg). The animals received either GA (50, 100 and 150 mg/kg) or saline as the vehicle for 14 consecutive days. We measured depression and anxiety levels of the rats by conducting the behavioral tail suspension (TST), elevatedplusmaze (EPM), and novelty suppressed feeding (NSF) tests. Histological analyses were then used to de- termine the cell densities of different hippocampal subdivisions. The data were analyzed with ANOVA and Tukey's post hoc test. RESULTS: GA administration ameliorated anxiety and depression in the behavioral tests. The cell densities in the CA1, CA2, CA3 and DG hippocampal subdivisionsfrom GA-treat- ed rats were higher than saline treated rats. CONCLUSION: GA treatment against TMT-induced hippocampal degeneration altered cellular loss in the hippocampus and ameliorated the depression-anxiety state in rats.

The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats.

Nigella sativa (NS) has been suggested to have neuroprotective and anti-seizures properties. The aim of current study was to investigate the effects of NS hydro-alcoholic extract on neural damage after pentylenetetrazole (PTZ) - induced repeated seizures. The rats were divided into five groups: (1) control (saline), (2) PTZ (50 mg/kg, i.p.), (3-5) PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 (100, 200 and 400 mg/kg of NS extract respectively, 30 min prior to each PTZ injection on 5 consecutive days). The passive avoidance (PA) test was done and the brains were then removed for histological measurements. The PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 groups had lower seizure scores than PTZ group (P < 0.01 and P < 0.001). The latency to enter the dark compartment by the animals of PTZ group was lower than control in PA test (P < 0.01). Pre-treatment by 400 mg/kg of the extract increased the latency to enter the dark compartment (P < 0.05). Meanwhile, different doses of the extract inhibited production of dark neurons in different regions of hippocampus (P < 0.001). The present study allows us to suggest that the NS possesses a potential ability to prevent hippocampal neural damage which is accompanied with improving effects on memory.

Xenotransplantation of human adipose derived mesenchymal stem cells in a rodent model of Huntington's disease: motor and non-motor outcomes.

Human mesenchymal stem cells (hMSCs) have been presented as alternative sources of cells to be transplanted into the brain in neurodegenerative disorders. In this regard, the efficacy of hMSCs transplants in reducing motor and non-motor deficits in a quinolinic acid (QA) rat model of Huntington's disease (HD) was tested in the present study. After unilateral lesions in striatum by QA, the isolated and purified hMSCs from liposuction of healthy male donors were transplanted into the damaged striatum of the rats. The cells were stably transfected with a vector containing TurboGFP and JRed to make it possible to trace them after transplantation. Animals were tested by motor and non-motor function tests at different times after the cell transplantation. The hMSCs survived 7 weeks in the brains. An improvement was observed in behavioral tests such as apomophine-induced rotation, hanging wire, and rotarod for the hMSC-treated rats. Anxiety like behaviors were decreased in hMSCs-treated animals when they were examined using open field, elevated plus maze, light and dark box, and novelty suppressed feeding tests. Compared to QA, the hMSCs treatment decreased motor activities. These results confirmed the potential efficacy of hMSCs in treatment of behavioral defects in HD. Generally, the data demonstrated that xenologous transplantation of hMSCs could be considered as an ideal candidate for treatment of neurodegenerative diseases, especially HD.

The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats.

Regarding the therapeutic properties of Nigella sativa (NS), the effects of the plant hydro - alcoholic extract on learning, memory and brain tissues oxidative damage were investigated in penthylenetetrazole (PTZ) - induced repeated seizures. There were 4 experimental groups including: 1- control group; received saline, 2- PTZ group ; received saline and PTZ (50 mg/Kg, i.p) , 3-PTZ- NS 200 and 4- PTZ- NS 400 ; received 200 and 400 mg/Kg of NS extract respectively, before PTZ injection in 5 consecutive days. Seizure scores were lower in PTZ - NS 200 and 400, furthermore the seizure onset latencies were higher in these groups than PTZ group (P<0.05 and P<0.01 ). In Morris water maze, the time spent in target quadrant by PTZ group was lower than control group (P<0.05); while, 400 mg/Kg of the extract increased it (P<0.01). In the passive avoidance test, delay time to enter the dark by PTZ group was lower than control at 1 and 24 hours after training (P<0.01- P<0.001); while, 400 mg/Kg of the extract increased it (P<0.05). The total thiol concentration in hippocampal and cortical tissues of PTZ group was reduced while, MDA concentration was higher than control (p<0.05 - p<0.001). Administration of the extract increased the total thiol and decreased the MDA concentrations (p<0.01- p<0.001). It is concluded that the hydro-alcoholic extract of NS possess beneficial effects on learning and memory impairments in repeated seizures model which is accompanied by antioxidant effects in the brain.

Histopathological and behavioral assessment of toxin-produced cerebellar lesion: a potent model for cell transplantation studies in the cerebellum.

OBJECTIVE: The cerebellum is a key structure involved in coordinated motor planning, cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. MATERIALS AND METHODS: In this experimental study, slow administration of quinolinic acid (QA, 5 µl of 200 µmol, 1 µl/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student's t test. RESULTS: The QA treated group showed marked motor learning deficits on the rotating rod test (p=0.0001), locomotor asymmetry on the cylinder test (p=0.0001), dysmetria on the beam balance test (p=0.0001), abnormalities in neuromuscular strength on the hang wire test (p=0.0001), spatial memory deficits in the Morris water maze (MWM, p=0.001) and fear conditioned memory on the passive avoidance test (p=0.01) over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p=0.001) and granular cell density (p=0.0001) in the lesioned hemisphere of the cerebellum. CONCLUSION: Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.

Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism.

Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and the range of interests and activities. However, neuronal processing studies have suggested that hyper-perception, hyper-attention, and enhanced memory, which may lie at the heart of most autistic symptoms. Pregnant Wistar rats were administered by either Valproic Acid (VPA, 500mg/kg) or Phosphate Buffer Saline (PBS) during fetal neural tube development on embryonic day 12.5. All offspring were subjected to various tests. The present study examined social interaction, repetitive behaviors, nociception and tactile threshold, anxiety as well as spatial memory. Histological analyses of cells in five regions of the hippocampus were done to determine neuronal density in both groups. A single intra-peritoneal injection of VPA to pregnant rats produced severe autistic-like symptoms in the offspring. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions, enhanced stereotyped, repetitive behaviors, increased nociception threshold and anxiety at postnatal day (PND) 30 and PND 60. The Morris water maze learning paradigm revealed enhanced spatial memory at PND 60. Furthermore, histological analysis showed that the neuronal density in five separate regions of hippocampus (CA1, CA2, CA3, Dentate gyrus and Subiculum) were increased at PND 67. This work suggests that early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological and neuroanatomical hypotheses. This study provides further evidence to support the notion that spatial memory and hippocampal cell density are increased in this animal model of autism.

Evaluating the biodegradability of Gelatin/Siloxane/Hydroxyapatite (GS-Hyd) complex in vivo and its ability for adhesion and proliferation of rat bone marrow mesenchymal stem cells.

Recent studies have shown that the use of biomaterials and new biodegradable scaffolds for repair or regeneration of damaged tissues is of vital importance. Scaffolds used in tissue engineering should be biodegradable materials with three-dimensional structures which guide the growth and differentiation of the cells. They also tune physical, chemical and biological properties for efficient supplying of the cells to the selected tissues and have proper porosity along with minimal toxic effects. In this manner, the study of these characteristics is a giant stride towards scaffold design. In this study, Gelatin/Siloxane/Hydroxyapatite (GS-Hyd) scaffold was synthesized and its morphology, in vivo biodegradability, cytotoxic effects and ability for cell adhesion were investigated using mesenchymal stem cells (MSCs). The cells were treated with different volumes of the scaffold suspension for evaluation of its cytotoxic effects. The MSCs were also seeded on scaffolds and cultured for 2 weeks to evaluate the ability of the scaffold in promoting of cell adhesion and growth. To check the biodegradability of the scaffold in vivo, scaffolds were placed in the rat body for 21 days in three different positions of thigh muscle, testicle, and liver and they were analyzed by scanning electron microscopy (SEM) and weight changes. According to the results of the viability of this study, no cytotoxic effects of GS-Hyd scaffold was found on the cells and MSCs could adhere on the scaffold with expanding their elongations and forming colonies. The rate of degradation as assessed by weight loss was significant within each group along with significant differences between different tissues at the same time point. SEM micrographs also indicated the obvious morphological changes on the surface of the particles and diameter of the pores through different stages of implantation. The greatest amount of degradation happened to the scaffold particles implanted into the muscle, followed by testicle and liver, respectively.

Bone marrow derived mesenchymal stem cell transplantation in cerebellar degeneration: a behavioral study.

In addition to its key role in complex motor function, the cerebellum is increasingly recognized to have a role in cognition. Thus, motor and cognitive deficits can be associated with cerebellar degeneration. After unilateral lesion in cerebellum (folia VI) was caused by Quinolinic acid, CM-DiI labeled mesenchymal stem cells (MSCs), which were isolated and purified from bone marrow, were transplanted into the damaged folium. Motor function was assessed using the cylinder test, rotarod, hanging wire and beam balance during 6 weeks after transplantation. Cognitive function was assessed using the Morris water maze learning paradigm in 3 weeks after transplantation. Six weeks after transplantation surviving MSCs were detectable in QA-treated animals. The MSC-transplanted group showed markedly improved functional performance in spatial memory, motor learning, locomotor asymmetry, dysmetria, abnormality in neuromuscular strength and equilibrium 2-6 weeks compared with the controls. We found that cerebellar lesions produced deficits (folia VI) in motor and cognitive aspects of a spatial task. The results indicate that transplantation of MSCs can significantly reduce the behavioral abnormalities of these animals during six weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow derived adult stem cells promises for treatment of cerebellar diseases.

Neuroprotective effects of mesenchymal stem cell transplantation in animal model of cerebellar degeneration.

BACKGROUND: The cerebellum has been considered a key structure for the processes involved in sensorimotor integration ultimately leading to motor planning and execution of coordinated movement. Thus, motor deficits and behavioral changes can be associated with cerebellar degeneration. METHODS: Here, the chemical neurotoxin pyridine-2,3-dicarboxylic acid (quinolinic acid, QA) used to create partially cerebellar degeneration in adult Wistar rats suitable for use in stem cell transplantation studies. Stereotaxicaly administration of QA (0.2 mmol) in the right cerebellar hemisphere (folia VI) caused noticeable motor disturbance in all treated animals. Forty-eights hours after causing lesion, rat bone marrow-derived mesenchymal stem cells (MSCs) were transplanted into damaged cerebellar hemisphere. We investigated the role of MSC transplantation in forms of motor and non-motor learning that involves the cerebellum and its neuroprotective effects in Purkinje cells loss. RESULTS: CM-Dil labeling showed that the transplanted MSCs survived and migrated in the cerebellum 6 weeks after transplantation. The MSC-transplanted group showed markedly improved functional performance on the rotating rod test (P≤0.0001) and beam walking test (P≤0.0001) during 6 weeks compared with the controls. For non-motor learning, we used passive avoidance learning test in 3 weeks after transplantation. The results showed that MSC transplantation prevented the development of memory deficit caused by cerebellar degeneration (P≤0.001). Stereological analysis in 6 weeks after transplantation showed that QA significantly decreases Purkinje cells in vehicle-treated rats and MSC transplantation is neuroprotective and decreases Purkinje cell loss in MSC-treated rats (P≤0.0001). CONCLUSION: The results indicate that transplantation of MSCs can significantly reduce the behavioral and neuroanatomical abnormalities of these animals during 6 weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow-derived adult stem cells promises for treatment of cerebellar diseases.

Systemic transplantation of mesenchymal stem cells can reduce cognitive and motor deficits in rats with unilateral lesions of the neostriatum.

Huntington's disease (HD) is an inherited neurodegenerative disorder that usually occurs in the third or fourth decades of life. Stem cell therapy is one of the approaches for HD treatment. Since mesenchymal stem cells (MSCs) have the ability to migrate into the lesioned site, we transplanted rat bone marrow-derived MSCs intravenously, following unilateral intrastriatal lesion made by quinolinic acid (QA) in Wistar rats. QA administration caused widespread neuropathological deficits similar to those found in HD, including impairments in motor and cognitive functions. Animals receiving MSCs exhibited significant improvement in motor and cognitive performance compared with sham group animals that did not receive cells. Animals were tested by apomorphine-induced rotations, beam walk, cylinder and hang wire tests at different times after cell transplantation. Results indicate that systemic transplantation of MSCs can significantly reduce the behavioral abnormalities of these animals. This method of systemic injection has a great advantage over invasive surgical techniques for transplantation of cells at the lesioned site.