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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.
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Melatonina , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Ratas , Animales , Neuronas Dopaminérgicas , Melatonina/farmacología , Melatonina/uso terapéutico , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Ratas Sprague-Dawley , Sustancia Negra , Estrés Oxidativo , Muerte Celular , Glutatión/metabolismoRESUMEN
Congenital abnormalities of the uterus result primarily from embryological maldevelopment of the paramesonephric ducts and have been associated with pregnancy complications, reduced fertility, and other adverse fetal outcomes. While such abnormalities are rare, affected patients should be correctly managed to improve psychological, sexual, and reproductive outcomes. This review intends to elucidate the impact of congenital uterine abnormalities on fertility and pregnancy outcomes. We also present the available management methods and discuss the role of assisted reproductive technologies (ART) to benefit affected women. This review clearly shows that although these disorders are generally not lethal, they critically impact the patient's reproductive health. The fertility rate of patients with uterine congenital abnormalities depends on the severity of the condition. Reproductive endocrinologists and infertility specialists must be considered as active parts of the interdisciplinary treatment team for such patients. ART practices are reasonably successful at managing fertility problems of women with these abnormalities.
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Anomalías Urogenitales , Útero , Femenino , Fertilidad , Humanos , Embarazo , Resultado del Embarazo/epidemiología , Técnicas Reproductivas Asistidas , Anomalías Urogenitales/complicaciones , Anomalías Urogenitales/epidemiología , Anomalías Urogenitales/terapiaRESUMEN
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; 17ß-HSD III: 17ß-Hydroxysteroid Dehydrogenase III; 21-OHD: 21-hydroxylase deficiency; 5α-RD-2: 5α-reductase-2.
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Trastornos del Desarrollo Sexual , Femenino , Hormona Folículo Estimulante , Humanos , Hormona Luteinizante , Masculino , Embarazo , Reproducción , Desarrollo SexualRESUMEN
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).
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Medios de Cultivo Condicionados/farmacología , Células Madre Mesenquimatosas/fisiología , Nanofibras/administración & dosificación , Regeneración Nerviosa/fisiología , Poliésteres/administración & dosificación , Neuropatía Ciática/terapia , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Masculino , Ratones , Regeneración Nerviosa/efectos de los fármacos , Ratas , Ratas Wistar , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patología , Nervio Ciático/fisiología , Neuropatía Ciática/patología , Andamios del TejidoRESUMEN
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.
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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.
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Dronabinol/farmacología , Hipocampo/efectos de los fármacos , Memoria/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Atrofia/metabolismo , Atrofia/patología , Reacción de Prevención/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Ratas , Ratas WistarRESUMEN
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.
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Regeneración Nerviosa/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Nervio Ciático/fisiopatología , Activador de Tejido Plasminógeno/administración & dosificación , Andamios del Tejido , Animales , Axotomía , Células Cultivadas , Masculino , Ratones , Ratas , Nervio Ciático/patologíaRESUMEN
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-1ß 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.
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Enfermedad de Huntington , Animales , Atrofia , Pulpa Dental , Modelos Animales de Enfermedad , Humanos , Enfermedad de Huntington/inducido químicamente , Enfermedad de Huntington/terapia , Inflamación/inducido químicamente , Nitrocompuestos , Propionatos , Ratas , Células MadreRESUMEN
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 100â¯dB at the frequency ranges of 500-8000â¯Hz, 4â¯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.
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Ruido , Corteza Prefrontal/anatomía & histología , Animales , Apoptosis/fisiología , Corticosterona/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Neuronas/citología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas WistarRESUMEN
Human chorionic mesenchymal stem cells (HCMSCs) have been recognized as a desirable choice for cell therapy in neurological disorders such as Parkinson's disease (PD). Due to invaluable features of HCMSCs including their immunomodulatory and immunosuppressive properties, easily accessible and less differentiated compared to other types of MSCs, HCMSCs provide a great hope for regenerative medicine. Thus, the purpose of this study was to determine the in vitro and in vivo efficacy of HCMSCs-derived dopaminergic (DA) neuron-like cells with regard to PD. Initially, HCMSCs were isolated and underwent a 2-week DA differentiation, followed by in vitro assessments, using quantitative real-time polymerase chain reaction, immunocytochemistry, patch clamp recording, and high-performance liquid chromatography. In addition, the effects of implanted HCMSCs-derived DA neuron-like cells on the motor coordination along with stereological alterations in the striatum of rat models of PD were investigated. Our results showed that under neuronal induction, HCMSCs revealed neuron-like morphology, and expressed neuronal and DA-specific genes, together with DA release. Furthermore, transplantation of HCMSCs-derived DA neurons into the striatum of rat models of PD, augmented performance. Besides, it prevented reduction of striatal volume, dendritic length, and the total number of neurons, coupled with a diminished level of cleaved caspase-3. Altogether, these findings suggest that HCMSCs could be considered as an attractive strategy for cell-based therapies in PD.
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Conducta Animal/fisiología , Cuerpo Estriado/patología , Neuronas Dopaminérgicas/trasplante , Células Madre Mesenquimatosas/citología , Actividad Motora/fisiología , Neurogénesis/fisiología , Enfermedad de Parkinson Secundaria/cirugía , Animales , Enfermedad de Parkinson Secundaria/patología , Enfermedad de Parkinson Secundaria/fisiopatología , RatasRESUMEN
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.
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Muerte Celular/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Corteza Prefrontal/efectos de los fármacos , Conservadores Farmacéuticos/farmacología , Timerosal/farmacología , Ácido Tióctico/farmacología , Animales , Masculino , Tamaño de los Órganos/efectos de los fármacos , Corteza Prefrontal/crecimiento & desarrollo , Ratas , Ratas WistarRESUMEN
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.
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Animales , Masculino , Ratas , Médula Espinal/fisiopatología , Médula Espinal/patología , Nervio Ciático/fisiología , Nervio Ciático/lesiones , Ratas Wistar , Axotomía , Electromiografía , Células del Asta AnteriorRESUMEN
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.
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Neuronas Adrenérgicas/efectos de los fármacos , Locus Coeruleus/efectos de los fármacos , Melatonina/farmacología , Fármacos Neuroprotectores/farmacología , Privación de Sueño , Animales , Masculino , Ratas , Ratas WistarRESUMEN
The spatial arrangement of the cell is important and considered as underlying mechanism for mathematical modeling of cell to cell interaction. The ability of cells to take on the characteristics of other cells in an organism, it is important to understand the dynamical behavior of the cells. This method implements experimental parameters of the cell-cell interaction into the mathematical simulation of cell arrangement. The purpose of this research was to explore the three-dimensional spatial distribution of anterior horn cells in the rat spinal cord to examine differences after sciatic nerve injury. Sixteen Sprague-Dawley male rats were assigned to control and axotomy groups. Twelve weeks after surgery, the anterior horn was removed for first- and second-order stereological studies. Second-order stereological techniques were applied to estimate the pair correlation and cross-correlation functions using a dipole probe superimposed onto the spinal cord sections. The findings revealed 7% and 36% reductions in the mean volume and total number of motoneurons, respectively, and a 25% increase in the neuroglial cell number in the axotomized rats compared to the control rats. In contrast, the anterior horn volume remained unchanged. The results also indicated a broader gap in the pair correlation curve for the motoneurons and neuroglial cells in the axotomized rats compared to the control rats. This finding shows a negative correlation for the distribution of motoneurons and neuroglial cells in the axotomized rats. The cross-correlation curve shows a negative correlation between the motoneurons and neuroglial cells in the axotomized rats. These findings suggest that cellular structural and functional changes after sciatic nerve injury lead to the alterations in the spatial arrangement of motoneurons and neuroglial cells, finally affecting the normal function of the central nervous system. The experimental protocol was reviewed and approved by the Animal Ethics Committee of Shahid Beheshti University of Medical Sciences (approval No. IR.SBMU.MSP.REC1395.375) on October 17, 2016.
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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.
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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.
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Enfermedad de Alzheimer/cirugía , Péptidos beta-Amiloides/toxicidad , Apoptosis , Gliosis , Hipocampo/cirugía , Plasticidad Neuronal , Fragmentos de Péptidos/toxicidad , Células de Sertoli/trasplante , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Animales , Modelos Animales de Enfermedad , Hipocampo/patología , Hipocampo/fisiopatología , Aprendizaje/fisiología , Masculino , Ratas , Ratas Wistar , Células de Sertoli/metabolismo , Vimentina/metabolismoRESUMEN
In Parkinson's disease, nigral dopamine neurons are lost and the structure of the striatum is progressively degraded. These events lead to a substantial neuronal loss in the striatum, changing spatial pattern of the neurons and glial cells, and associated cellular connections. Therefore, the aim of this study was to develop a new insight into whether the Parkinson's disease causes a change in the spatial arrangement of the neurons and glial cells in the striatum. Nigral injection of 6-hydroxydopamine led to a significant reduction in the total number of the neurons, an increase in the number of striatal glial cells, and disruption in the spatial arrangement of glial and neuronal cells in the Parkinson's disease-induced group, compared to the control group. The data support the idea that in Parkinson's disease, the function of the striatum is disturbed by both the loss of neurons and an increase in the number of glial cells, culminating in the disordered spatial distribution of these cells.
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Cuerpo Estriado/efectos de los fármacos , Neuroglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Oxidopamina/farmacología , Trastornos Parkinsonianos/tratamiento farmacológico , Sustancia Negra/efectos de los fármacos , Simpaticolíticos/farmacología , Animales , Cuerpo Estriado/citología , Modelos Animales de Enfermedad , Masculino , Neuroglía/patología , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Sustancia Negra/citologíaRESUMEN
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.
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Citocinas/metabolismo , Mastocitos/efectos de los fármacos , Microglía/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Timerosal/farmacología , Animales , Animales Recién Nacidos , Recuento de Células , Interleucina-1beta/metabolismo , Masculino , Mastocitos/metabolismo , Microglía/metabolismo , Neuroinmunomodulación/efectos de los fármacos , Corteza Prefrontal/citología , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Methamphetamine (Meth) is recognized as one of the most important new distributed abused drug that causes severe damage to the different parts of the brain, especially hippocampus. Previous studies have demonstrated that Meth can induce apoptosis and cell death in the brain. In this study, we evaluated the long-term effects of Meth abuse in the CA1 region of postmortem hippocampus. Postmortem molecular and histological analysis was performed for five non-addicted subjects and five Meth addicted ones. Iba-1 (microglia) and glial fibrillary acidic protein, GFAP (astrocytes) expression were assayed by western blotting and immunohistochemistry (IHC) methods. Histopathological assessment was done with stereological counts of hippocampal cells stained with hematoxylin and eosin (H and E). Tunel staining was used to detect DNA damage in human brains. In addition, protein-protein interaction analysis network was investigated. Western blotting and immunohistochemistry assay showed overexpression of GFAP and Iba-1 protein in the CA1 hippocampal region of Meth users' brain. Stereological analysis in the CA1 region revealed increased neuron degeneration. Furthermore, significant apoptosis and cell death were confirmed by Tunel assay in the hippocampus. The prominent role of TLR4, IL1B, CASP1, and NLRP3 in the molecular mechanism of Meth was highlighted via PPI network analysis. Chronic Meth use can induce GFAP and Iba-1 upregulation and neuronal apoptosis in the CA1 region of the postmortem hippocampus.