RESUMEN
In spite of recent advances in the treatment of epilepsy, up to 35% of people living with the condition do not respond to accessible anti-epileptic drugs (AEDs) and continue to experience regular, devastating and potentially life-threatening seizures. Neuronal death is a significant feature of epilepsy in humans and experimental models. It has been reported that apelin, an endogenous ligand for the angiotensin-1-like receptor (APJ), has anticonvulsive as well as protective effects in some neurodegenerative situations. In the current study, we investigated the effects of apelin-13 on pentylenetetrazole (PTZ)-induced neurotoxicity in rat's brain primary culture. Cell injury was induced by 20mM PTZ and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species (ROS) and mitochondrial membrane potential were determined by fluorescence spectrophotometry methods. Markers of apoptosis were determined by immunohistochemistry. The data showed that PTZ caused a loss of cell viability and mitochondrial membrane potential. In addition, intracellular reactive oxygen species, intracellular calcium, COX-2 and caspase-3 positive cells were increased in PTZ-treated cells. Incubation of the cells with aplein-13 (10µM) elicited protective effect and reduced markers of cell damage and death. The results suggest that apelin-13 has protective effects against PTZ-induced toxicity and such effects are accompanied by its calcium blocking, antioxidant and, anti-inflammatory and anti-apoptotic properties.
Asunto(s)
Supervivencia Celular/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Neuroglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Pentilenotetrazol/efectos adversos , Sustancias Protectoras/farmacología , Animales , Antiinflamatorios/farmacología , Anticonvulsivantes/farmacología , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Caspasa 3/metabolismo , Técnicas de Cocultivo/métodos , Ciclooxigenasa 2/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neuroglía/metabolismo , Neuronas/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismoRESUMEN
Stem cells have the ability to self renew and are therefore a good source for cell therapy following ischemia. In this study, we transplanted adult rat neural stem cells (NSCs) by lumbar puncture (LP) to investigate whether these cells can migrate and differentiate into neurons or glial cells, thereby improving functional outcome in cerebral ischemia. Transient ischemia was induced in adult rats (n=16) for 1h. Three days after the induction of ischemia, NSCs obtained from the subventricular zone of adult rats were injected into ischemic animals (n=8) by LP at the level of L6-S1. Improved recovery of the coordination of movement on the 1st, 7th, 14th, 21st and 28th days after the injury was examined by the Rotarod test and compared with non-transplanted ischemic animals (n=8). The presence of NSCs in the brain tissue of the animals was examined by immunohistofluorscence and immunohistochemical techniques. The coordination of movement in ischemic animals that received neural stem cells was improved significantly (P<0.05) compared with untreated ischemic animals. Cells labeled with PKH26 were observed in the ischemic area of brain tissue sections. The alkaline phosphatase test and immunohistochemical techniques demonstrated a gathering of NSCs in the lateral ventricle. A number of cells which expressed neuronal and astrocytic cell markers had migrated from the lateral ventricle to the subjacent brain parenchyma. NSCs injected by LP were able to migrate to the ischemic tissue and differentiate into neural-like cells. These differentiated cells may have improved the coordination in movement in the ischemic animals injected with NSCs.
Asunto(s)
Células Madre Adultas/trasplante , Ataque Isquémico Transitorio/terapia , Células-Madre Neurales/trasplante , Células Madre Adultas/citología , Células Madre Adultas/fisiología , Animales , Diferenciación Celular , Movimiento Celular , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/fisiopatología , Masculino , Movimiento , Células-Madre Neurales/citología , Células-Madre Neurales/fisiología , Neuroglía/patología , Neuroglía/fisiología , Neuronas/patología , Neuronas/fisiología , Ratas , Ratas Wistar , Punción EspinalRESUMEN
BACKGROUND AND THE PURPOSE OF THE STUDY: Cerebral ischemia is one of the main causes of long term disability and death in aged populations. Many herbal drugs and extracts have been used for the treatment of cerebral ischemia induced insults. This study was designed to investigate the protective effect of Semelil (ANGIPARS™), a new herbal drug, on focal cerebral ischemia in male rats. MATERIAL AND METHODS: MALE RATS WERE DIVIDED INTO FIVE GROUPS: sham-operated, ischemic animals treated with distilled water as vehicle, ischemic animals treated with 1, 10 and 100 mg/kg of Semilil respectively. Middle cerebral artery occlusion (MCAO) model was used in NMRI rats and neuronal injury analyzed in hippocampal CA1 sector after 48 hrs of Middle Cerebral Artery (MCAO). RESULTS: Results of this study showed that treatment with semelil attenuated ischemic damages and has positive effects on focal cerebral ischemia.