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1.
Toxicol Res (Camb) ; 12(5): 783-795, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37915479

RESUMEN

The present study was designed to evaluate whether elderberry (EB) effectively reduces inflammation and oxidative stress in hippocampal cells to modify seizure damage. Seizure was induced in rats by the injection of pentylenetetrazol (PTZ). In the Seizure + EB group, EB powder was added to the rats' routine diet for eight consecutive weeks. The study included several behavioral tests, immunohistopathology, Voronoi tessellation (to estimate the spatial distribution of cells in the hippocampus), and Sholl analysis. The results in the Seizure + EB group showed an improvement in the behavioral aspects of the study, a reduction in astrogliosis, astrocyte process length, number of branches, and intersections distal to the soma in the hippocampus of rats compared to controls. Further analysis showed that EB diet increased nuclear factor-like 2 expression and decreased caspase-3 expression in the hippocampus in the Seizure + EB group. In addition, EB protected hippocampal pyramidal neurons from PTZ toxicity and improved the spatial distribution of hippocampal neurons in the pyramidal layer and dentate gyrus. The results of the present study suggest that EB can be considered a potent modifier of astrocyte reactivation and inflammatory responses.

2.
J Chem Neuroanat ; 112: 101903, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33278568

RESUMEN

Cellular transplant therapy is one of the most common therapeutic strategies used to mitigate symptoms of neurodegenerative diseases such as Huntington's disease (HD). Briefly, the main goal of the present study was to investigate HD's motor deficits through the olfactory ecto-mesenchymals stem cells (OE-MSC) secretome. OE-MSCs were characterized immunophenotypically by the positive expression of CD73, CD90 and CD105. Also, three specific markers of OE-MSCs were obtained from the nasal cavity of human volunteers. The main features of OE-MSCs are their high proliferation, ease of harvesting and growth factor secretion. All animals were randomly assigned to three groups: control, 3-NP + vehicle treated and 3-NP + Cell groups. In both experimental groups, the subjects received intraperitoneal 3-NP (30 mg/kg) injections once a day for five consecutive days, followed by the bilateral intra-striatal implantation of OE-MSCs in the 3-NP + Cell group. Muscular function was assessed by electromyography and rotarod test, and the locomotor function was evaluated using the open field test. According to our findings, striatal transplants of OE-MSCs reduced microglial inflammatory factor, the tumor necrosis factor (TNFα) in the 3-NP + Cell group, with a significant reduction in RIP3, the markers of necroptosis in striatum. In addition to the remarkable recovery of the striatal volume after engraftment, the motor activities were enhanced in the 3-NP + cell group compared to the 3-NP + vehicle group. Taken together, our results demonstrated the in vivo advantages of OE-MSCs treatment in an HD rat model with numerous positive paracrine effects including behavioral and anatomical recovery.


Asunto(s)
Cuerpo Estriado/cirugía , Enfermedad de Huntington/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Actividad Motora/fisiología , Necroptosis/fisiología , Animales , Conducta Animal/fisiología , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Humanos , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Ratas , Prueba de Desempeño de Rotación con Aceleración Constante , Resultado del Tratamiento
3.
J Mol Neurosci ; 70(7): 1153-1163, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32166479

RESUMEN

To date, no certain cure has been found for patients with degenerative cerebellar disease. In this trial, we examined the in vivo and in vitro neuroprotective effects of Sertoli cells (SCs) on alleviating the symptoms of cerebellar ataxia. Testicular cells from an immature male rat were isolated and characterized by immunocytochemical analysis for somatic cell markers (anti-Mullerian hormone, vimentin). The protein assessment had already confirmed the expression of neurotrophic factors of glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial factor (VEGF). In vitro neuroprotective impact of SCs was determined after exposing PC12 cells to Sertoli cell-conditioned media (SC-CM) and H2O2, simultaneously. Afterwards, ataxia rat models were induced by a single dose of 3-AP (3-acetylpyridin), and 3 days later, SCs were bilaterally implanted. Motor and neuromuscular activity test were conducted following SC transplantation. Finally, immunohistochemistry against RIPK3 and Iba-1 was done in our generation. The in vivo results revealed substantial improvement in neuromuscular response, while ataxia group exhibited aggravated condition over a 28-day period. Our results suggested enhanced motor function and behavioral characteristics due to the ability of SCs to suppress necroptosis and consequently extend cell survival. Nevertheless, more studies are required to affirm the therapeutic impacts of SC transplantation in human cerebellar ataxia. In vitro data indicated cell viability was increased as a result of SC-CM with a significant reduction in ROS.


Asunto(s)
Ataxia Cerebelosa/terapia , Movimiento , Necroptosis , Células de Sertoli/trasplante , Trasplante de Células Madre/métodos , Animales , Células Cultivadas , Ataxia Cerebelosa/etiología , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Masculino , Células PC12 , Piridinas/toxicidad , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Células de Sertoli/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vimentina/genética , Vimentina/metabolismo
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