RESUMEN
The present study investigates the neuroprotective effects of modafinil-coated nanoparticle in rats' hippocampal CA1 region. Male Wistar rats (n = 48) were randomly divided into four groups. Then middle cerebral artery occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. Modafinil (100 mg/kg) or modafinil-coated nanoparticle (100 mg/kg) was given to the rats as an oral gavage once a day. Infarct volume, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neuronal nuclear protein (NeuN) and Caspase-3 and, Caspase-8 as apoptotic genes were measured in the hippocampal CA1 region. Cresyl violet staining revealed that modafinil nanoparticle significantly decreased the neurodegeneration. Reverse transcription polymerase chain reaction results showed that modafinil nanoparticle use significantly increased the expression of neurotrophic factors (even more than modafinil alone group; p = .01). Moreover, the apoptotic markers were significantly decreased in nanoparticle modafinil (MN group); p < .05). The western blot analysis and Immunohistochemistry results confirmed the neuroprotective and anti-apoptotic effects of modafinil nanoparticle. This study's results showed that the use of modafinil-coated nanoparticle has neuroprotective effects by increasing neurotrophic factors and reducing apoptosis after MCAO in the CA1 area of the hippocampus. However, further studies are needed especially, in human samples.
Asunto(s)
Nanopartículas , Fármacos Neuroprotectores , Animales , Apoptosis , Factor Neurotrófico Derivado del Encéfalo , Factor Neurotrófico Derivado de la Línea Celular Glial , Hipocampo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Modafinilo , Neuronas , Fármacos Neuroprotectores/farmacología , Proteínas Nucleares , Ratas , Ratas WistarRESUMEN
Systemic treatments for ischemic stroke as a disease with high disability and death have been yet unsuccessful. Combined treatments can potentially cause better results in treatment of patients with Stroke. In this study we assessed the neuroprotective effect of modafinil-coated gold nanoparticles (AuNPs) and mesenchymal stem cell (MSC) in ischemic stroke rats. Stem cells and AuNPs offer great promise for new medical treatments. 60 male Wistar rats were randomly divided into five groups (12 in each group): (1) the group that developed middle cerebral artery occlusion (MCAO or ischemia), (2) the normal group (control), (3) the MCAO group that received MSC (C + MCAO), (4) the MCAO group that received MSC and modafinil (CM + MCAO), and (5) the MCAO group that received MSC and modafinil-coated AuNPs (CMN + MCAO). Middle Cerebral Artery Occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. The filament was located in the internal carotid artery for 60 min and then removed. Modafinil-coated AuNPs (100 mg/kg) or Modafinil (100 mg/kg) were given to the rats as an oral gavage, once a day in the morning time. Finally, infarct volume, BDNF (Brain-derived neurotrophic factor), GDNF (Glial cell-derived neurotrophic factor), NeuN (neuronal nuclear protein) expression, and cell apoptosis in brain were analyzed. The brain infarct volume and apoptosis significantly decreased and BDNF, NeuN, and GDNF increased in C + MCAO, CM + MCAO, and CMN + MCAO groups compared to ischemia. CMN + MCAO groups did not show significant difference in these factors compared to control group. These results demonstrated that the administration of stem cells and Modafinil-coated AuNPs at the same time had a good effect on ischemic brain injuries. It happened through increasing neurotrophic factors and decreasing brain cell apoptosis.